Necrotising autoimmune myopathy (NAM): antibodies seem to be specific markers in aiding diagnosis

Dalakas, Marinos C.

doi:10.1136/jnnp-2016-313418

Cited by 16 publications

(9 citation statements)

References 4 publications

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“…There is no uniform approach to the treatment of anti-HMGCR myopathy [16,[22][23][24], nor are there a described severity score [2] or treat to target recommendations [25]. The 224th ENMC definition of severe anti-HMGCR myopathy was the presence of walking difficulties and/or dysphagia, while partial remission was defined as an improvement ≥ 110% of MMT-8 and/or CK levels, the latter remaining greater than or equal to twice the normal range, i.e., ≥ 500 UI/ L [16].…”

Section: Discussionmentioning

confidence: 99%

Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients

et al. 2020

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Objective: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. Methods: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. Results: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment.Conclusion: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

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Section: Discussionmentioning

confidence: 99%

Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients

et al. 2020

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“…Up to 65% of patients with NAM are positive for non-pathogenic antibodies against cytoplasmic signal recognition particle (SRP) and 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) 76 , 84 – 86 . In this condition, necrotic muscle fibres are strongly invaded by macrophages and contain sarcolemmal deposits of the MAC, the extent of which correlates with the extent of fibre necrosis, as generally seen in necrotic fibres from any cause 77 , 87 , 88 .…”

Section: Complement In Neurological Diseasesmentioning

confidence: 99%

Complement in neurological disorders and emerging complement-targeted therapeutics

2020

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The human complement system is an effector of innate and adaptive humoral immunity. The system comprises soluble membrane-bound proteins (opsonins) that act collectively to recognize pathogens and non-self material and subsequently initiate opsonization and phagocytosis or lysis of pathogens. The proteolytic fragments that derive from complement activation can be targeted by white blood cells and endothelial cells, leading to extravasation and migration of immune cells at the sites of inflammation. Other physiological functions of complement include timely removal of altered and senescent self, tissue remodelling, cell lysis, chemotaxis, opsonization, inflammation and immune cell stimulation 1-4. Complement activation products link the innate and adaptive immune systems by acting directly on receptors on T cells and B cells or by modulating dendritic cell functions 5-8. Disruption of the delicate coordination required for complement activation and control is fundamental in the pathogenic mechanism of several autoimmune neurological disorders, and is even emerging as a contributor in some neurodegenerative diseases. As a result, interest is increasing in targeting complement as a therapeutic approach to prevent ongoing tissue destruction in several difficult-to-treat neurological diseases. In this Review, we provide an overview of the main components of the initial complement activation pathways, the lytic pathway and the factors associated with inappropriate complement activation or control in disease initiation and progression. We consider the role of complement in the tissue destruction that is responsible for the genesis of the most common autoimmune neurological diseases, including complement-mediated myopathies, myasthenia gravis, neuropathies and CNS disorders. We also discuss the role of complement in some neurodegenerative disorders, including Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), Huntington disease, traumatic brain injury and even schizophrenia. Finally, we discuss emerging complement-targeted therapies, such as monoclonal antibodies, fusion proteins and cyclic peptides, that inhibit the functions of individual complement proteins, especially therapies that disrupt the lytic pathway. Some of these therapeutic agents have been approved or are being tested in phase I-III clinical trials and promise to change the therapeutic armamentarium for treatment of neurological conditions that respond poorly to existing immunotherapies.

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“…It is reported that statin myopathy is associated with the presence of HMGCR antibodies and causes a necrotizing myopathy in the affected muscles. 29,30 In addition, HCQ-induced myopathy is a rare condition which may cause proximal muscle weakness and cardiomyopathy and the muscle biopsy shows curvilinear bodies and vacuolar changes. 31 Finally, novel studies highlight that anti-Ku antibodies have been reported in a wide spectrum of autoimmune diseases, sometimes in association with IM.…”

Section: Discussionmentioning

confidence: 99%

Sjögren Syndrome Associated with Inflammatory Muscle Diseases

Migkos

Sarmas

Somarakis

et al. 2018

MJR

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This work is licensed under and Creative Commons Attribution-NonCommercial 4.0 International License. CASE REPORT INTRODUCTION Sjögren Syndrome (SS) is a chronic autoimmune inflammatory disease that primarily affects the exocrine glands and has also a variety of extraglandular manifestations. 1-6 SS can occur as a distinct disease entity (primary SS) or in the context of an underlying autoimmune rheumatic disease (secondary SS) mainly rheumatoid arthritis, systemic lupus erythematosus, scleroderma and others. 7-10 Inflammatory myopathies (IM) is a heterogeneous group of disorders characterized by chronic inflammation of striated muscle and skin. They share features of skeletal muscle weakness and elevated serum levels of muscle enzymes. 11,12 Muscle involvement is a frequent clinical ©Migkos MP,

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Necrotising autoimmune myopathy (NAM): antibodies seem to be specific markers in aiding diagnosis

Cited by 16 publications

References 4 publications

Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients

Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients

Complement in neurological disorders and emerging complement-targeted therapeutics

Sjögren Syndrome Associated with Inflammatory Muscle Diseases

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