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Idiopathic inflammatory myopathies

Abstract

Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that IIM are systemic inflammatory disorders. Different myositis-specific auto-antibodies have been identified and, on the basis of clinical, histopathological and serological features, IIM can be classified into several subgroups — dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the auto-antigens of the immune reactions in these subgroups is crucial to improving outcomes. New, more homogeneous subgroups defined by auto-antibodies may help define disease mechanisms and will also be important in future clinical trials for the development of targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.

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Fig. 1: Manifestations of IIM.
Fig. 2: Clinical manifestations in patients with DM and anti-TIF1, anti-NXP2 and anti-Mi-2 auto-antibodies.
Fig. 3: Clinical manifestations in patients with DM with anti-MDA5 and anti-SAE auto-antibodies.
Fig. 4: Clinical manifestations of antisynthetase syndrome.
Fig. 5: Clinical manifestations in IMNM.
Fig. 6: Clinical manifestations of IBM.
Fig. 7: Typical histopathological changes in IIM subgroups.
Fig. 8: Common pharmacological and other therapies for IIM except for IBM.
Fig. 9: Treatment considerations in patients with refractory myositis based on clinico-serological presentation.

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Acknowledgements

I.E.L. was funded by the Swedish Research Council, the Swedish Rheumatism Association, King Gustav V 80-year Foundation and Stockholm County Council (ALF Project). J.V. acknowledges the support from the Czech Ministry of Health - Conceptual Development of Research Organization 00023728 (Institute of Rheumatology). M.H. was funded by the Swedish Research Council, The Marianne and Marcus Wallenberg Foundation, The Professor Nanna Svartz Foundation and the King Gustaf V 80-year Foundation. A.L.M. and F.W.M. were supported in part by the Intramural Research Program of the NIH, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and/or the National Institute of Environmental Health Sciences.

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Introduction (I.E.L.); Epidemiology (M.H.); Mechanisms/pathophysiology (A.L.M. and F.W.M.); Diagnosis, screening and prevention (M.F. and J.V.); Management (R.A.); Quality of life (L.C-S.); Outlook (I.E.L.); Overview of Primer (I.E.L.).

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Correspondence to Ingrid E. Lundberg.

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Competing interests

I.E.L. has received research funding from AstraZeneca and Bristol Myers Squibb, has served on advisory boards for Corbus Pharmaceutical, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, Janssen, and Pfizer and has stock shares in Roche and Novartis. M.F. has received research funding and speakers fee from Abbvie, Amgen, Eli Lilly, Japan Blood Product Organization, Kyowa-Kirin, Maruho, Novartis, Sanofi and Taiho. J.V. has been on Speakers Bureaus of Abbvie, Biogen, MSD, Pfizer, Roche, Sanofi, and UCB and has consulted for Abbvie, Argenx, Boehringer, Eli Lilly and Octapharma. R.A. receives research funding from BMS, Mallinckrodt, Genentech, and Pfizer and has served as a consultant for BMS, Mallinckrodt, Pfizer, Orphazyme, Octapharma, Kyverna, Kezar, Janssen, Csl Behring, Corbus, Boehringer-Ingelheim, AstraZeneca, Argenx, Alexion, Q32 and Abbvie. L.C-S. has research support from Pfizer, Corbus, and Kezar and has served on advisory boards for UCB (not myositis related), Janssen, Boehringer-Ingelheim, Mallinckrodt, Serono, Argenx, Roivant and Dysimmune Disease Foundation (DDF), and received compensation for consultancy work from Guidepoint and Allogene. She is also a patent holder on an assay for anti-HMGCR auto-antibodies for which she received royalty payments from Inova Diagnostics. A.L.M. is a patent holder on an assay for anti-HMGCR auto-antibodies but does not receive any royalties. The other authors declare no competing interests.

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Nature Reviews Disease Primers thanks Yves Allenbach; Jan De Bleecker; Marianne de Visser; Samuel Shinjo; and Lucy Wedderburn, who co-reviewed with Meredyth Wilkinson, for their contribution to the peer review of this work.

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Lundberg, I.E., Fujimoto, M., Vencovsky, J. et al. Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7, 86 (2021). https://doi.org/10.1038/s41572-021-00321-x

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