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We read with interest the article by the European League Against Rheumatism/American College of Rheumatology on the classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.1 While we believe these criteria will help with the diagnosis of most of the major subgroups of idiopathic inflammatory myopathies, we anxiously await society guidelines that direct physicians on how best to individualise the treatment for specific subgroups of this disease.
For example, one subgroup we seek immediate direction is on the treatment of patients with antibodies directed against the melanoma differentiation associated protein 5 (anti-MDA5). This antibody is typically identified in patients with clinically amyopathic dermatomyositis (CADM), and it is now increasingly appreciated that some of these individuals develop a highly aggressive form of lung disease that causes severe tissue destruction and often fatal respiratory failure.2 Consistent with this clinical course, we recently diagnosed a patient with anti-MDA5 associated CADM in our hospital who developed rapidly progressive respiratory failure within a span of only a few days and died within just 1 week of his hospitalisation; this was despite our early initiation of high dose corticosteroids. Further, limited autopsy of the chest revealed pathological findings consistent with the acute respiratory distress syndrome (ARDS), including diffuse alveolar damage and prominent hyaline membrane deposition. Notably, our review of the literature indicates that our clinical experience is not unique as nearly 50% of individuals with anti-MDA-associated lung involvement appear to have a similar clinical course, emphasising the devastating nature of this condition.3–5
The general approach to the treatment of lung disease in patients with idiopathic inflammatory myopathies, including CADM, is to initiate immunosuppressant drugs usually with a regimen containing high dose corticosteroids.6 However, we wonder if it is now time to reconsider this treatment approach for anti-MDA-5 associated lung disease given our emerging understanding of the mechanisms that may underlie its development. For example, it is known that MDA5 is a viral RNA binding protein that is important for activating anti-viral immune responses. As such, it is believed that antibodies directed against MDA-5 act to either activate or inhibit its activity, thereby triggering enhanced or blunted immune responses to viral infections, respectively. It seems reasonable to assume that the prevention of lung disease might depend on removing anti-MDA5 antibodies from the circulation much like the approach used for other antibody-mediated lung conditions such as Goodpasture’s syndrome or Granulomatosis with Polyangiitis, which often rely on the use of plasmapheresis and anti-B lymphocyte therapies.
In addition to above strategies, we in the pulmonary community also wonder whether we should begin reconsidering our approach to the management of respiratory failure once it develops in patients with anti-MDA-5 antibodies. For example, we postulate whether treatments utilised for other aggressive forms of acute respiratory failure (eg, ARDS) should be considered so that patients can theoretically be supported for extended periods. This would include strategies such as fluid restriction, lung protective ventilation and the various salvage therapies often used for ARDS like prone ventilation, neuromuscular blockade and extra-corporeal membrane oxygenation. Our hope is that if we move toward a more personalised approach to the treatment of anti-MDA5-associated lung disease we can improve outcomes for what appears to be one of the most, if not the most, aggressive forms of rheumatic lung disease.
Handling editor Josef S Smolen
Contributors All three authors of this article contributed to the writing of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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