The four main types of inflammatory muscle disease — dermatomyositis, polymyositis, necrotizing autoimmune myositis, and inclusion-body myositis — are summarized. Pathogenesis, differential diagnosis, and treatment approaches are discussed.

/pdf/inflammatory-muscle-diseases-5270giyz06.pdf

Inflammatory Muscle Diseases

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)60954-X.pdf

Immunopathogenic mechanisms of systemic autoimmune disease

Results from clinical trials of biologic anti-TNF drugs performed in the late 1990s confirmed the biological relevance of TNF function in the pathogenesis of chronic noninfectious inflammation of joints, skin and gut, which collectively affects 2-3% of the population. Up to April 2009, more than two million patients worldwide have received the first marketed drugs, namely the monoclonal anti-TNF antibodies infliximab and adalimumab and the soluble TNF receptor etanercept. All three are equally effective in rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, but, for not clearly defined reasons, only the monoclonal antibodies are effective in inflammatory bowel disease. About 60% of patients who do not benefit from standard nonbiologic treatments for these diseases respond to TNF antagonists. Less than half of responding patients achieve complete remission of disease. Importantly, some of those patients with rheumatoid arthritis in whom long-term anti-TNF therapy induced disease remission remain disease-free after discontinuation of any kind of treatment. There are not yet reliable predictors of which patients will or will not respond on anti-TNF therapy, whereas subsequent loss of an initial clinical response occurs frequently. The spectrum of efficacy anti-TNF therapies widens to include diseases such as systemic vasculitis and sight-threatening uveitis. While paradoxical new adverse effects are recognized, i.e. exacerbation or development of new onset psoriasis, reactivation of latent tuberculosis remains the most important safety issue of anti-TNF therapies. Clinical practice guidelines and consensus statements on the criteria of introduction, duration of treatment and cessation of TNF antagonists, including safety issues, are under constant revision as data from longer periods of patient exposure accumulate. It is hoped that more efficacious drugs that will ideally target the deleterious proinflammatory properties of TNF without compromising its protective role in host defense and (auto)immunity will be available in the near future.

The First Decade of Biologic TNF Antagonists in Clinical Practice: Lessons Learned, Unresolved Issues and Future Directions

Type I and II interferon signatures in Sjogren's syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjogren's related lymphomagenesis

The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including systemic lupus erythematosus, Sjogren syndrome, myositis, systemic sclerosis, and rheumatoid arthritis. In normal immune responses, type I interferons have a critical role in the defence against viruses, yet in many rheumatic diseases, large subgroups of patients demonstrate persistent activation of the type I interferon pathway. Genetic variations in type I interferon-related genes are risk factors for some rheumatic diseases, and can explain some of the heterogeneity in type I interferon responses seen between patients within a given disease. Inappropriate activation of the immune response via Toll-like receptors and other nucleic acid sensors also contributes to the dysregulation of the type I interferon pathway in a number of rheumatic diseases. Theoretically, differences in type I interferon activity between patients might predict response to immune-based therapies, as has been demonstrated for rheumatoid arthritis. A number of type I interferon and type I interferon pathway blocking therapies are currently in clinical trials, the results of which are promising thus far. This Review provides an overview of the many ways in which the type I interferon system affects rheumatic diseases.

Type I interferon in rheumatic diseases

Objective: To investigate the effect of the tumour necrosis factor (TNF) blocking agent infliximab in patients with treatment-resistant inflammatory myopathies. Methods: A total of 13 patients with refractory polymyositis (PM), dermatomyositis (DM), or inclusion body myositis (IBM) were treated with 4 infliximab infusions (5 mg/kg body weight) over 14 weeks. Outcome measures included myositis disease activity score with improvement defined according to The International Myositis Assessment and Clinical Studies Group (IMACS), and MRI. Repeated muscles biopsies were investigated for cellular infiltrates, major histocompatibility complex (MHC) class I and II, TNF, interleukin (IL)1α, IL6, high mobility group box chromosomal protein 1 (HMGB-1), interferon γ (IFNγ), myxovirus resistance protein A (MxA) and membrane attack complex (MAC) expression. Type I IFN activity was analysed in sera. Results: Nine patients completed the study. Three patients discontinued due to adverse events and one due to a discovered malignancy. Three of the completers improved by ⩾20% in three or more variables of the disease activity core set, four were unchanged and two worsened ⩾30%. No patient improved in muscle strength by manual muscle test. At baseline, two completers had signs of muscle inflammation by MRI, and five at follow-up. T lymphocytes, macrophages, cytokine expression and MAC deposition in muscle biopsies were still evident after treatment. Type I IFN activity was increased after treatment. Conclusions: Infliximab treatment was not effective in refractory inflammatory myopathies. In view of radiological and clinical worsening, and activation of the type I IFN system in several cases, infliximab is not an alternative treatment in patients with treatment-resistant myositis.

https://ard.bmj.com/content/annrheumdis/67/12/1670.full.pdf?67%2F12%2F1670=

A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies

Idiopathic inflammatory myopathies, such as polymyositis (PM), may present with general symptoms such as fever and fatigue and only minimal muscle weakness, making it difficult to make a definite diagnosis and provide adequate treatment. Here a case is described in which interstitial lung disease was the first and most prominent manifestation of PM. Later, when muscle weakness became apparent and inflammatory muscle disease was suspected the first muscle biopsy was non-diagnostic. However, magnetic resonance imaging (MRI) scans of the clinically weak thigh muscles showed high signal on T2 weighted images, suggesting muscle inflammation more proximal to the first biopsy site. A second biopsy at this site disclosed typical histopathological findings for myositis. After treatment with prednisolone in combination with cyclophosphamide both pulmonary and muscle function improved.
CONCLUSION—MRI scans of muscles may be helpful in selection of a site for muscle biopsy in patients with suspected inflammatory myopathy when a first muscle biopsy turns out to be negative. Additionally, patients with interstitial lung disease of unknown cause should be tested for muscular function to exclude an associated inflammatory muscle disorder.

https://ard.bmj.com/content/annrheumdis/60/4/423.full.pdf

H Einarsdottir

Papers

A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies

MRI guided muscle biopsy confirmed polymyositis diagnosis in a patient with interstitial lung disease.