Myositis specific autoantibodies – What is the clinical usefullness?
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The authors describe the myositis-specific and myositis-associated antibodies (MSA-s) in idiopathic inflammatory myopathies and dermatomyositis, with particular emphasis on aspects of clinical relevancy. The frequency and clinical significance of MSA-s in 50 dermatomyositis patients at our Clinic are presented. The most common MSA, anti-TIF-1 antibodies were found in 14% of our dermatomyositis patients and they were associated with cancers, in accordance with previous reports. For patients with a high tumor risk, a comprehensive tumor research using all imaging devices should be performed.Keywords:
Clinical Significance
The concentration of soluble interleukin 2 receptor was determined in serum samples from 19 patients with polymyositis/dermatomyositis by an enzyme linked immunosorbent assay (ELISA). The concentration of soluble interleukin 2 receptor in serum samples from patients with polymyositis/dermatomyositis was higher than that in samples from normal subjects.
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In this review article the author stresses the fact that it is difficult to find a classification which fulfils all clinical, morphological and pathogenetic criteria and that is not advisable to separate the late onset myopathies of M. Shy from the group of polymyositis. Treatment with high doses of corticosteroids is useful in most cases, whereas in individual patients immunosuppressive agents may be tried.
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The idiopathic inflammatory myopathies, collectively called myositis, are a heterogeneous group of diseases of which polymyositis and dermatomyositis are the best known. These heterogeneous group of chronic disordes sharing the clinical symptom of muscle weakness and, in typical cases, inflammatory cell infiltrates in muscle tissue. There are four major types of idiopathic inflammatory myopathies: dermatomyositis, polymyositis, inclusion body myositis and immune-mediated necrotizing myopathies (autoimmune necrotizing myopathies). Clinical and histopatological distinctions between these conditions suggest that different pathogenic processes underline each of the inflammatory myopathies.
Inclusion body myositis
Pathogenesis
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Idiopathic inflammatory dermatomyopathies have been historically defined by broad clinical and pathological criteria,whose spectrum of clinical illness includes clinically amyopathic dermatomyositis,classic dermatomyositis and polymyositis.Clinical manifestations of this entity are diverse with various degrees of muscular,cutaneous and pulmonary involvement.Myositis-specific autoantibodies and myositis-associated autoantibodies are frequently detected in sera of patients with idiopathic inflammatory dermatomyopathies,some of which are closely associated with the clinical characteristics and specific for the diagnosis of idiopathic inflammatory dermatomyopathies. Recently, some autoantibodies such as anti-clinically amyopathic dermatomyositis (CADM) 140 antibody and anti-small ubiquitin-like modifier activating enzyme (SAE) antibody have been detected in sera of patients with idiopathic inflammatory dermatomyopathies,which are not closely associated with the initiation of myositis and should not be classified as myositis-specific autoantibodies,but as an independent subset of antibodies specific for idiopathic inflammatory dermatomyopathies.
Key words:
Dermatomyositis; Autoantibodies; Myositis
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Inclusion body myositis
Inflammatory myopathy
Muscle weakness
Muscle disorder
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The clinical, laboratory and pathologic characteristics in eight cases of polymyositis or dermatomyositis are described, with certain observations concerning clinical course and therapy. The author considers polymyositis and dermatomyositis to be variants of a single pathologic entity which can be separated from rheumatoid disease. Es describite le characteristics clinic, laboratorial, e pathologic de octo casos de polymyositis o dermatomyositis. Observationes relative al curso clinic e al therapia es includite. Le autor considera polymyositis e dermatomyositis como variantes de un sol entitate pathologic que pote esser differentiate ab morbo rheumatoide.
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OBJECTIVE:To analyze the prevalence of myositis-specific and myositis-associated autoantibodies and their clinical correlations in a large series of patients with dermatomyositis/polymyositis.METHOD: This cross-sectional study enrolled 127 dermatomyositis cases and 95 polymyositis cases.The diseaserelated autoantibody profiles were determined using a commercially available blood testing kit.RESULTS: The prevalence of myositis-specific autoantibodies in all 222 patients was 34.4%, whereas myositisassociated autoantibodies were found in 41.4% of the patients.The most frequently found autoantibody was anti-Ro-52 (36.9%), followed by anti-Jo-1 (18.9%), anti-Mi-2 (8.1%), anti-Ku (4.1%), anti-SRP (3.2%), anti-PL-7 (3.2%), anti-PL-12 (2.7%), anti-PM/Scl75 (2.7%), and anti-PM/Scl100 (2.7%).The distributions of these autoantibodies were comparable between polymyositis and dermatomyositis, except for a higher prevalence of anti-Jo-1 in polymyositis.Anti-Mi-2 was more prevalent in dermatomyositis.Notably, in the multivariate analysis, anti-Mi-2 and anti-Ro-52 were associated with photosensitivity and pulmonary disorders, respectively, in dermatomyositis.Anti-Jo-1 was significantly correlated with pulmonary disorders in polymyositis.Moreover, anti-Ro-52 was associated with anti-Jo-1 in both diseases.No significant correlation was observed between the remaining autoantibodies and the clinical and/or laboratory findings.CONCLUSIONS: Our data are consistent with those from other published studies involving other populations, although certain findings warrant consideration.Anti-Ro-52 and anti-Jo-1 were strongly associated with one another.Anti-Ro-52 was correlated with pulmonary disorders in dermatomyositis, whereas anti-Jo-1 was correlated with pulmonary alterations in polymyositis.
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Polymyositis and dermatomyositis are two inflammatory muscle diseases of unknown origin mediated by a dysimmune mechanism via a cytotoxic effect against the muscle fiber in polymyositis and a humoral effect against the muscle vessels in dermatomyositis. First line treatment of polymyositis and dermatomyositis is still based on corticosteroid therapy. In case of failure, corticosteroid dependence, or intolerance, a second line treatment using immunosuppressors or polyvalent human intravenous immunoglobulins (IVIg) is usually associated. We report our experience with IVIg in the treatment of 50 patients with myositis unresponsive to corticosteroids and immunosuppressors. Thirty-five patients had polymyositis and 15 had dermatomyositis. We discuss the possible mechanisms and their precise role in the therapeutic armamentarium in these dysimmune diseases.
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The idiopathic inflammatory myopathies, collectively named myositis, can be subclassified into polymyositis, dermatomyositis and inclusion body myositis. Patients with polymyositis and dermatomyositis usually respond to immunosuppressive treatment, at least with partial improvement, whereas patients with inclusion body myositis often are treatment resistant. These differences in treatment response suggest different pathogenic mechanisms and that treatment strategies should be different in these different subsets of myositis. Only a few controlled trials have been performed in patients with myositis, thus treatment recommendations are mainly based on case series and clinical experience. This lecture will include update on (1) Pharmacological and non-pharmacological treatment (exercise) for polymyositis and dermatomyositis; (2) The role of biologics in myositis (2) Outcome measures for polymyositis and dermatomyositis, and (3) Treatment recommendations for inclusion body myositis. For polymyositis and dermatomyositis there is scientific data to support that treatment should be based on a combination of immunosuppressive treatment and physical exercise. The basis of treatment is still glucocorticoids often with high starting doses e.g. 0.75- 1 mg/kg/day needed. Improvement of muscle performance is often slow and high doses of glucocorticoids may be needed for 1 month of more. As side effects of glucocorticoids are common and some patients may not respond favorably to glucocorticoid treatment alone, most experts suggest another immunosuppressive agent as glucocorticoid saving and to improve the effects of treatment. The most often used drugs are methotrexate and azathioprine. So far the experience of biologics in treatment of polymyositis and dermatomyositis is limited but the results of a placebo-controlled trial using rituximab will be discussed. Physical exercise in combination with immunosuppressive drugs has clear beneficial effects in established disease on muscle performance and health related quality of life and should be recommended. Furthermore, physical exercise seems to be safe also in early phases of disease. The most important outcome measure in polymyositis and dermatomyositis is muscle performance, strength and endurance, and the influence of disease activity or damage respectively on these measures. In addition, both polymyositis and dermatomyositis, are systemic inflammatory diseases and other organs are frequently involved and therefore also need to be measured. The variability of disease manifestations of polymyositis and dermatomyositis is captured using the International Myositis Assessment and Clinical Studies Group (IMACS) core set of disease activity. Inclusion body myositis (IBM) is a slowly progressive disorder, where the importance of the immune system in the pathophysiology is unclear. Some patients experience a partial improvement with glucocorticoids in the initial phases of disease whereas other patients do not respond at al. therefore IBM is an important differential diagnosis to refractory polymyositis. Characteristics of IBM will be discussed as well as results of some pharmacological interventions.
Disclosure of Interest
None DeclaredInclusion body myositis
Antisynthetase syndrome
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