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Nature Reviews. Rheumatology Jan 2024Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis. Although the aetiology and... (Review)
Review
Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis. Although the aetiology and pathology remain unclear, increasing evidence suggests that viral infection is a potential trigger of MDA5-DM. Multiple factors, including T cells, B cells, neutrophils and macrophages, are implicated in the pathophysiology of MDA5-DM. Distinctive skin rashes, rapidly progressive interstitial lung disease, peripheral lymphopenia and elevated serum ferritin levels are the most prominent clinical and laboratory features of MDA5-DM. Concomitant infection is a common complication of MDA5-DM. The proper evaluation of patients with MDA5-DM requires knowledge of the disease heterogeneity and clinical course variability. Several biomarkers, including serum levels of anti-MDA5 antibodies and biomarkers related to macrophage activation, have been identified as useful tools for monitoring disease activity and prognosis. MDA5-DM shows a poor response to conventional glucocorticoid and immunosuppressant therapy and has a poor overall prognosis. Therefore, there is an urgent need to explore the key pathogenic mechanisms of MDA5-DM and develop novel therapeutic options for patients. This Review discusses recent clinical progress and pathogenic findings of MDA5-DM.
Topics: Humans; Dermatomyositis; Retrospective Studies; Lung Diseases, Interstitial; Autoantibodies; Interferon-Induced Helicase, IFIH1; Prognosis; Biomarkers
PubMed: 38057474
DOI: 10.1038/s41584-023-01054-9 -
Current Opinion in Rheumatology Jan 2024This review focuses on treatments for anti-MDA5 antibody-positive dermatomyositis (MDA5-DM), which is a subgroup of dermatomyositis and characterized by frequent rapidly... (Review)
Review
PURPOSE OF REVIEW
This review focuses on treatments for anti-MDA5 antibody-positive dermatomyositis (MDA5-DM), which is a subgroup of dermatomyositis and characterized by frequent rapidly progressive interstitial lung disease and the high mortality rate. Despite conventional immunosuppressive therapies, there are still refractory cases. Newer treatment options are needed.
RECENT FINDINGS
The triple combination therapy (high-dose glucocorticoids, calcineurin inhibitor, and intravenous cyclophosphamide) improved patient survival compared to high-dose glucocorticoids and step-wise addition of the immunosuppressants. The triple therapy now has been widely used, but there are still refractory cases. In addition to the conventional-type immunosuppressants, recently the efficacy of Janus kinase inhibitors, biologic agents such as rituximab, plasma exchange, and polymyxin B perfusion for refractory MDA5-DM patients have been reported. However, the majority of those reports regarding new treatments are limited to case series, retrospective studies, and small single-arm studies. Adding antifibrotic drugs to immunosuppressive therapies might have some ancillary benefits.
SUMMARY
Several new therapies for MDA5-DM patients have emerged, although the optimal use of those therapies is still unknown. Further research and evidence accumulation will be needed. It is also noted that the intensive immunosuppressive therapies are associated with the higher infection risk.
Topics: Humans; Dermatomyositis; Retrospective Studies; Lung Diseases, Interstitial; Autoantibodies; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1
PubMed: 37682061
DOI: 10.1097/BOR.0000000000000979 -
Current Rheumatology Reports Aug 2023Idiopathic inflammatory myopathies (IIM) are a complex family of autoimmune systemic disorders which often affect muscle and/or skin. IIM cause significant morbidity and... (Review)
Review
PURPOSE OF REVIEW
Idiopathic inflammatory myopathies (IIM) are a complex family of autoimmune systemic disorders which often affect muscle and/or skin. IIM cause significant morbidity and mortality, but optimal treatment is uncertain. This review provides a practical guide for using intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) in the management of IIM, including dermatomyositis (DM), polymyositis (PM), immune-mediated necrotizing myositis (IMNM), and spontaneous inclusion body myositis (IBM), based on relevant recent literature and experience. We summarize pertinent considerations when using IVIG in special circumstances, including myositis-related dysphagia, interstitial lung disease (ILD), calcinosis cutis, and pregnant patients. This review also discusses IVIG safety, available formulations, and costs.
RECENT FINDINGS
While IVIG has been used de facto for severe IIM for over 30 years, prior clinical trials of IVIG were notably limited. Recently, however, IVIG has proven safe and effective against IIM in several high-impact publications, including a large prospective, randomized placebo-controlled phase III study in DM. IVIG is useful against both muscular and extra-muscular manifestations in many types of IIM. It can be used as a first-line, steroid-sparring agent or as add-on to other treatments, tailored to specific clinical IIM scenarios. It is generally well-tolerated and has good safety profile, but accessibility and cost still limit its use.
Topics: Humans; Immunoglobulins, Intravenous; Dermatomyositis; Prospective Studies; Myositis; Polymyositis; Autoimmune Diseases; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic
PubMed: 37261663
DOI: 10.1007/s11926-023-01105-w -
JAMA Dermatology Sep 2023
Topics: Humans; Dermatomyositis; Paraneoplastic Syndromes; Biopsy
PubMed: 37405743
DOI: 10.1001/jamadermatol.2023.1013 -
Inflammopharmacology Feb 2024Sjögren's syndrome (SS) is characterised as keratoconjunctivitis sicca (dry eyes), xerostomia (dry mouth) commonly associated with salivary gland enlargement, and is...
Sjögren's syndrome (SS) is characterised as keratoconjunctivitis sicca (dry eyes), xerostomia (dry mouth) commonly associated with salivary gland enlargement, and is referred to as Primary Sjögren's syndrome. It is known as Secondary Sjögren's syndrome when it occurs in patients, with connective tissue disease, such as rheumatoid arthritis, systemic lupus erythematosus, polyarthritis nodosa, polymyositis, and systemic sclerosis. SS has also been associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation, human immunodeficiency syndrome (AIDS), hepatitis C infection (HCV), chronic biliary cirrhosis, neoplastic and myeloplastic syndromes, fibromyalgia, and chronic fatigue syndrome.
Topics: Humans; Sjogren's Syndrome; Arthritis, Rheumatoid; Fibromyalgia; Lupus Erythematosus, Systemic; Scleroderma, Systemic
PubMed: 37195497
DOI: 10.1007/s10787-023-01222-z -
Indian Journal of Pediatrics Nov 2023Idiopathic inflammatory myopathies (IIMs) are a diverse group of diseases characterized by proximal muscle weakness and inflammation in skeletal muscle. Phenotypically,... (Review)
Review
Idiopathic inflammatory myopathies (IIMs) are a diverse group of diseases characterized by proximal muscle weakness and inflammation in skeletal muscle. Phenotypically, the subtypes include dermatomyositis, polymyositis, inclusion body myositis, and amyopathic dermatomyositis. The most common IIM in children is juvenile dermatomyositis (JDM). In contrast to adult dermatomyositis (DM), children are likely to have frequent relapses, vasculopathy, and long-term metabolic and other complications like lipodystrophy, insulin resistance, and calcinosis. Significant advances in our understanding of pathogenesis, disease course, and treatment of JDM has changed the therapeutic landscape and improved outcomes in children. Myositis-specific autoantibodies and myositis-associated autoantibodies have unique clinical associations, disease course and help predict response to therapy. A multidisciplinary approach including exercise programs and psychosocial support is essential. The first line of treatment is a combination of corticosteroids and methotrexate (MTX). Other targeted immunosuppressive therapy is used in refractory cases. Early recognition and timely referral to a specialist center remain pivotal to improving the mortality and morbidity associated with this disease.
PubMed: 37919486
DOI: 10.1007/s12098-023-04896-z -
Muscle & Nerve Oct 2023Intravenous immune globulin (IVIG) is an immune-modulating biologic therapy that is increasingly being used in neuromuscular disorders despite the paucity of... (Review)
Review
Intravenous immune globulin (IVIG) is an immune-modulating biologic therapy that is increasingly being used in neuromuscular disorders despite the paucity of high-quality evidence for various specific diseases. To address this, the AANEM created the 2009 consensus statement to provide guidance on the use of IVIG in neuromuscular disorders. Since then, there have been several randomized controlled trials for IVIG, a new FDA-approved indication for dermatomyositis and a revised classification system for myositis, prompting the AANEM to convene an ad hoc panel to update the existing guidelines.New recommendations based on an updated systemic review of the literature were categorized as Class I-IV. Based on Class I evidence, IVIG is recommended in the treatment of chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome (GBS) in adults, multifocal motor neuropathy, dermatomyositis, stiff-person syndrome and myasthenia gravis exacerbations but not stable disease. Based on Class II evidence, IVIG is also recommended for Lambert-Eaton myasthenic syndrome and pediatric GBS. In contrast, based on Class I evidence, IVIG is not recommended for inclusion body myositis, post-polio syndrome, IgM paraproteinemic neuropathy and small fiber neuropathy that is idiopathic or associated with tri-sulfated heparin disaccharide or fibroblast growth factor receptor-3 autoantibodies. Although only Class IV evidence exists for IVIG use in necrotizing autoimmune myopathy, it should be considered for anti-hydroxy-3-methyl-glutaryl-coenzyme A reductase myositis given the risk of long-term disability. Insufficient evidence exists for the use of IVIG in Miller-Fisher syndrome, IgG and IgA paraproteinemic neuropathy, autonomic neuropathy, chronic autoimmune neuropathy, polymyositis, idiopathic brachial plexopathy and diabetic lumbosacral radiculoplexopathy.
Topics: Humans; Child; Immunoglobulins, Intravenous; Dermatomyositis; Neuromuscular Diseases; Myasthenia Gravis; Guillain-Barre Syndrome; Myositis; Polyneuropathies; Myositis, Inclusion Body
PubMed: 37432872
DOI: 10.1002/mus.27922