Idiopathic Inflammatory Myopathies: Current Trends in Pathogenesis, Clinical Features, and Up-to-Date Treatment Recommendations

Abstract

Recently, there have been important advances in the understanding of the pathophysiologic features, assessment, and management of patients with a newly diagnosed idiopathic inflammatory myopathy (IIM). Myositis-specific autoantibodies have been identified to define patient subgroups and offer prognostic implications. Similarly, proinflammatory cytokines, such as interleukin 6 and type 1 interferon-dependent genes, may serve as potential biomarkers of disease activity in adult and juvenile patients with dermatomyositis (DM). Moreover, magnetic resonance imaging has become an important modality for the assessment of muscle inflammation in adult IIM and juvenile DM. Immune-mediated necrotizing myopathies also are being recognized as a subset of IIM triggered by medications such as statins. However, confusion exists regarding effective management strategies for patients with IIM because of the lack of large-scale, randomized, controlled studies. This review focuses primarily on our current management and treatment algorithms for IIM including the care of pediatric patients with juvenile DM. For this review, we conducted a search of PubMed and MEDLINE for articles published from January 1, 1970, to December 1, 2011, using the following search terms: idiopathic inflammatory myopathies, dermatomyositis, polymyositis, juvenile dermatomyositis, sporadic inclusion body myositis, inclusion body myositis, inflammatory myositis, myositis, myopathies, pathogenesis, therapy, and treatment. Studies published in English were selected for inclusion in our review as well as additional articles identified from bibliographies.

Inflammatory Muscle Diseases

“…Muscle atrophy is detected early in inclusion-body myositis, with selective atrophy of the quadriceps and forearm muscles, but it develops in all subtypes if the weakness is severe and chronic. Myalgia and muscle tenderness may occur, especially in patients with the antisynthetase syndrome (see the Glossary), 6,7 but if pain is severe and the weakness follows a "breakaway" pattern, in which the patient has difficulty sustaining effort, fasciitis or fibromyalgia should be ruled out.…”

“…Extramuscular manifestations may occur in all inflammatory myopathies, although they occur in inclusion-body myositis only in rare cases; these manifestations include systemic symptoms, such as fever, arthralgia, and Raynaud's phenomenon, as seen in the antisynthetase syndrome 4,6,7 ; cardiac arrhythmias or ventricular dysfunction, in relatively uncommon cases in which the affected cardiac muscle is clinically symptomatic; and pulmonary complications, due primarily to interstitial lung disease, which are reported in 10 to 40% of patients. 8 The prevalence of interstitial lung disease, a condition that is best detected with highresolution computed tomography, is as high as 70% among patients with anti-histidyl-transfer RNA (tRNA) synthetase (anti-Jo-1) or anti-melanoma differentiation-…”

“…14,15 Necrotizing autoimmune myositis occurs alone or after viral infections, in association with cancer, in patients with connective-tissue disorders such as scleroderma, or in patients taking statins, in whom the myopathy continues to worsen after statin withdrawal (if the myopathy improves within 4 to 6 weeks after discontinuation of statins, it was probably caused by toxic effects of the drug rather than by immune myopathy). 3,4,6,[14][15][16] Most patients with necrotizing autoimmune myositis have antibodies against signal recognition particle (SRP) or against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (see the Glossary). [14][15][16] …”

“…15,16 Anti-HMGCR, seen in 22% of persons with necrotizing autoimmune myositis, regardless of statin use, correlates with creatine kinase levels and strength. 31 Dermatomyositis-associated antibodies include anti-Mi-2, which is associated with the typical skin lesions; anti-MDA-5, which is associated primarily with amyopathic dermatomyositis or interstitial lung disease 4,6,16 ; and anti-transcriptional intermediary factor 1γ (anti-TIF-1γ) and anti-nuclear matrix protein 2 (anti-NXP-2), which are usually present in patients with cancer-associated adult dermatomyositis, 29 although their presence is influenced by geographic, racial, and genetic factors. Anti-cytosolic 5′-nucleotidase 1A (anti-cN1A) is detected in 60 to 70% of patients with inclusionbody myositis, 32,33 although the degree of sensi- tivity and specificity varies according to the method of detection used, and indicates B-cell activation.…”

“…They constitute a heterogeneous group of disorders that are best classified, on the basis of distinct clinicopathologic features, in four subtypes: dermatomyositis, polymyositis, necrotizing autoimmune myositis, and inclusion-body myositis (throughout this review, I use this term to refer specifically to sporadic inclusion-body myositis). [1][2][3][4][5][6] A fifth subtype, termed overlap myositis, is also beginning to be recognized. The identification of the correct subtype and the distinction of these conditions from other diseases that have characteristics that mimic these conditions is fundamental, because each subtype has a different prognosis and response to therapies.…”