ACR Convergence 2021—Idiopathic inflammatory myopathies (IIM) are heterogeneous, systemic diseases with muscle and/or skin as the primary targets, and diagnosing and treating these conditions correctly can be a major challenge for many rheumatologists. During the ACR Convergence 2021 Review Course, Rohit Aggarwal, MD, MS, professor of medicine, rheumatology and clinical immunology and co-director of the University of Pittsburgh Medical Center Myositis Center, provided an overview of this important topic.
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Many rheumatologists are familiar with the 1975 Bohan and Peter criteria for the diagnosis of dermatomyositis and polymyositis, but Dr. Aggarwal noted these criteria were developed years before the discovery of numerous myositis-associated autoantibodies that have greatly enhanced our understanding of these diseases.1,2 Given this and several other limitations of the Bohan and Peter criteria, the ACR and the European Alliance of Associations for Rheumatology (EULAR) worked together to publish classification criteria for adult and juvenile IIM in 2017.3
Sixteen variables were weighted and included in the final classification criteria, and a web-based calculator was developed to provide a score that represents the probability of a specific patient having an IIM. This setup allows researchers using the EULAR/ACR classification criteria to have flexibility in tailoring the inclusion criteria in a study to a certain level of sensitivity or specificity depending on the type of study considered.
In studying the performance of these criteria in a large, monocentric cohort of patients with IIM, Barsotti et al. evaluated 439 consecutive patients with a diagnosis of IIM at the Karolinska University Hospital, Sweden.4 The authors found the EULAR/ACR criteria had a higher sensitivity (87.7%) than the Bohan and Peter criteria (80.4%) and that the EULAR/ACR criteria demonstrated a high specificity (>98%) for the major IIM subgroups polymyositis, dermatomyositis and inclusion body myositis. Given this information, Dr. Aggarwal explained that these new classification criteria represent a great advancement in the field of myositis.
In discussing the epidemiology of IIM, Dr. Aggarwal noted these diseases are rare, with an incidence of about eight per one million patients. Aside from juvenile dermatomyositis, the typical age of onset of IIM is between the ages of 30 and 60, with specific forms of disease, such as inclusion body myositis (IBM), occurring most specifically in patients 50 and older. On that note, IBM is more common in male patients while other forms of IIM are seen more often in women than men in a ratio of about 2:1. Finally, although all ethnic groups can be affected by IIM, these diseases are most common in Black patients.
Dr. Aggarwal provided important clinical pearls with respect to the historical aspects of IIM. Although fatigue and myalgias can certainly be seen in patients with IIM, muscle weakness is a key element consistent across nearly all forms of these diseases. The onset of muscle weakness in dermatomyositis, polymyositis and juvenile dermatomyositis can be quite acute and the progression of weakness typically occurs over weeks to months—although with IBM a very slow progression over the course of years is the norm.
In contrast to metabolic myopathies, which often cause intermittent weakness, IIM demonstrates progressive, chronic weakness that tends to increase over time. When assessing for these diseases, it is important to evaluate for extra-muscular manifestations of myositis, such as dysphagia; signs and symptoms of cardiomyopathy; lung disease, which can manifest as interstitial lung disease or respiratory muscle weakness; arthritis; Raynaud’s phenomenon; rash; calcinosis; and/or such systemic symptoms as fevers and weight loss.
In any patient being evaluated for IIM, the clinician must also consider the possibility of metabolic myopathy, genetic myopathy, muscular dystrophy, thyroid disease and toxic myopathies that can be associated with alcohol or drug use, as well as with certain medications, such as statins and glucocorticoids.
Dr. Aggarwal stated the laboratory findings in IIM must be interpreted carefully and within the right clinical framework. Not only will creatine kinase and aldolase be elevated in many forms of IIM, so too will aspartate and alanine transaminases and lactate dehydrogenase. About 20% of patients with dermatomyositis, unlike polymyositis, will demonstrate normal muscle enzyme levels.
Specific autoantibodies correlate well with certain phenotypes within the category of IIM. For example, antibodies against signal recognition particle and HMG-CoA-reductase are commonly found in patients with immune-mediated necrotizing myopathy, whereas antibodies against melanoma differentiation-associated protein-5 (anti-MDA5) occur in patients with very specific skin findings (i.e., skin ulcerations, tender palmar papules), a propensity for severe and often rapidly progressive interstitial lung disease and frequent occurrence of clinically myopathy disease.
Additional studies that can aid in diagnosis include electromyogram and nerve conduction studies, magnetic resonance imaging of the muscles using specific myositis protocols and muscle biopsy.
Dr. Aggarwal concluded his lecture discussing treatments for IIM. First-line agents remain methotrexate and azathioprine, with second-line agents consisting of mycophenolate mofetil, tacrolimus and cyclosporine; a combination of first- and second-line agents can also be used in patients with disease that is refractory to methotrexate or azathioprine alone. Third-line agents include rituximab and cyclophosphamide, and such medications may be particularly appropriate for patients with interstitial lung disease. Experimental treatments at this time include ACTH gel, abatacept, and tofacitinib.
According to Dr. Aggarwal, treatment decisions should be based on the category of IIM; the specific phenotype of disease, as indicated by myositis-specific autoantibodies; the nature of organ involvement (e.g., skin disease, arthritis, interstitial lung disease); and a consideration of potential toxicities and side effects from treatment.
He noted that intravenous immunoglobulin (IVIG) is the only clearly evidence-based treatment that has been approved for use in IIM by the U.S. Food & Drug Administration.
In the ProDERM study, Dr. Aggarwal and colleagues enrolled patients with dermatomyositis on a stable dose of standard therapy (e.g., mycophenolate mofetil or methotrexate, glucocorticoids and hydroxychloroquine). These patients were then randomized to receive either 2 g/kg of IVIG or placebo every four weeks for 16 weeks. Patients who showed clinical deterioration in this period were switched to the alternative treatment and, at week 16, all patients on placebo and those without clinical deterioration on IVIG received 2 g/kg of IVIG every four weeks for 24 weeks. The researchers then measured the proportion of responders in each group with at least minimal improvement in the total improvement score (i.e., a composite response criteria) without deterioration at two consecutive visits up to week 16 and found that 79% of patients receiving IVIG and 44% of patients receiving placebo met this end point, respectively. Treatment-emergent adverse events were comparable in the IVIG and placebo groups.5
The talk was enlightening and served to show both how far the field of rheumatology has come in better understanding IIM, yet how far we have to go to best treat these diseases across the world.
Jason Liebowitz, MD, completed his fellowship in rheumatology at Johns Hopkins University, Baltimore, where he also earned his medical degree. He is currently in practice with Skylands Medical Group, N.J.
- Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344–347.
- Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975 Feb 20;292(8):403–407.
- Leclair V, Lundberg IE. New myositis classification criteria–What we have learned since Bohan and Peter. Curr Rheumatol Rep. 2018 Mar 17;20(4):18.
- Barsotti S, Dastmalchi M, Notarnicola A, et al. Performance of the new EULAR/ACR classification criteria for idiopathic inflammatory myopathies (IIM) in a large monocentric IIM cohort. Semin Arthritis Rheum. 2020 Jun;50(3):492–497.
- Aggarwal R, Charles-Schoeman C, Schessl J, et al. Prospective, double-blind, randomized, placebo-controlled phase III study evaluating efficacy and safety of octagam 10% in patients with dermatomyositis (“ProDERM Study”). Medicine (Baltimore). 2021 Jan 8;100(1):e23677.