Idiopathic Inflammatory Myopathies With Dr. Anthony Amato

Inflammatory myopathies are a large group of disorders associated with an inflammatory response targeting skeletal muscle. Treatment hinges on the use of evolving immunotherapies and diagnostic tools to quickly identify inflammatory myopathy, initiate appropriate therapy, and exclude underlying malignancy or infection of other organs.

In this episode, Katie Grouse, MD, FAAN speaks with Anthony A. Amato, MD, an author of the article “Idiopathic Inflammatory Myopathies” in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue.

Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California.

Dr. Amato is the Brigham and Women’s Hospital Distinguished Chair in Neurology and the director of neuromuscular research at Mass General Brigham, and is a professor of neurology at Harvard Medical School in Boston, Massachusetts.

Additional Resources

Read the article: Idiopathic Inflammatory Myopathies

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Full episode transcript available here

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.

Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Anthony Amato about his article on idiopathic inflammatory myopathies, which he wrote with Dr Kian Salajegheh. This article appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Welcome to the podcast, and please introduce yourself to our audience.

Dr Amato: Thank you. And I am Tony Amato. I'm in Boston at Mass General Brigham.

Dr Grouse: It is a distinct pleasure to have you here with us today, and I'm really excited to talk with you about your article. I thought it was a fantastic overview of the subject. And I'd like to start by asking what you hope will be the key takeaway for those who are reading this article.

Dr Amato: I think it's kind of basic: how to make a diagnosis, describe about the inflammatory myopathy as approach to, again, diagnosis, and then a little bit on pathogenesis, which… and kind of leading to the treatments, and hopefully we'll have more treatments based on the distinct pathogenesis in the future.

Dr Grouse: Can you give a brief overview of the categories of inflammatory myopathies you reviewed in your article?

Dr Amato: So, I mean, the major inflammatory myopathies, radiopathic inflammatory myopathies, are dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, and polymyositis. Now, that's been a big change, as you know. I mean it used to be, you know, we all started off it was dermato or poly. But I've kind of made a name for myself- a bad name for myself in the early 2000s saying, I'm not sure there's much of a thing called polymyositis. I think it's a hodgepodge and it's not distinct. And that's come to be, now most of those cases are- now we find out having antisynthetase syndrome or necrotizing myositis or IBM.

Dr Grouse: Could you walk us through your diagnostic approach with a patient in your clinic presenting with symptoms that are suspicious for inflammatory myopathy?

Dr Amato: So, you want to really make sure that they have inflammatory myopathy as opposed to some other kind of myopathy, a muscular dystrophy, for example. Taking family history first is going to be important, clueing in are they really weak or what they're complaining of is fatigue or muscle pain? Are they feel weak but what they really are complaining of is stiffness and rigidity from parkinsonism, or they have a sensory ataxia so they can't modulate? I want to know about other organ system involvement. Do they have a rash? Do they have joint swelling and pain that you might see with arthritis? Do they have shortness of breath that you might see with interstitial lung disease or ventilatory muscle weakness? Or do they have a cardiomyopathy? What kind of weakness do they have? Is it proximal weakness in the arms or legs? Getting out of a chair, climbing stairs. Do they have problems lifting their arms over their head---so, proximal weakness---or do they have more problems with grip, finger flexion, holding a pen, tripping? Do they have swallowing problems? Do they have ocular problems? So that's the big history on the exam. Again, I'm looking for pattern of involvement. So, on my exam, is there atrophy or weakness in muscles---you know, fasciculations---which would take it out of the motor? Is it mainly proximal? Is it distal? Again, is there ocular bulbar involvement? Is it symmetric, particularly in, like, the IBM? Most of the other inflammatory myopathies are going to be mainly and proximal and mainly symmetric. IBM is different, and that the- at least in the hands it's more distal, and it's finger flexors. So, you're looking at flexing the tips of the fingers, you're looking at the forearms, best looked at in a semipronated position to see if it's atrophied. And that leads you to an IBM if you see that. So that's the main things on exam.

Dr Grouse: That's a really helpful overview. I was wondering, in earlier training days, the convention was you- once you've suspected myopathy, you get your CK, you get your EMG, then that may give you the information you need for your diagnosis. It seems that things have been turned a little on their head. We're often skipping those things to go straight to the antibody testing. When should we be going for the myositis-specific antibodies before considering other things like EMG or muscle biopsy?

Dr Amato: I would always get a CK first. You know, in somebody who's weak. You know, the EMG, I don't need an EMG if the CK is two or three thousand. I mean, EMG is- localize it to, is it muscle, nerve, neuromuscular junction. If it's very elevated CK, it really doesn't help me there.  Sometimes if I have myotonic discharges or something that might make me think of a myotonic dystrophy or something else like that. But you can see that with the inflammatory myopathy. So, if I'm pretty sure of a myositis, I don't always do an EMG, or- unless I really need it to help guide what muscle biopsies I do. if I'm suspicious then on my exam and I see the CK---or they come to me already with the CK, which often happens, and it's very elevated---that's when I'll do the myositis-specific antibody panels if I'm really thinking that. And the important thing to know from that is, you have antibodies for dermatomyositis and antisynthetase that are on the panel that are available, and even signal recognition particle, which is a necrotizing myositis. But what's not on the panel is HMGCR antibodies, which is important because that's 70% of the necrotizing myocidites are HMGCR, and then the IBM antibody and T5-C1A is not on that. So, you need to order those separately. If somebody doesn't know, they order a myositis-specific antibody and think that it's all-inclusive, but it doesn't have IBM or the HMGCR antibody. And the other test that I sometimes will do is a skeletal-muscle MRI to help in the evaluation. Sometimes, not all the time, but I'm not sure it's a dystrophy, is it a myositis when I see a lot of STIR signal, which is edema. And you can still see STIR signal in a dystrophy and toxic. But sometimes I'll do it depending on whether I need a biopsy or not.

Dr Grouse: What is the benefit of an open biopsy versus a needle biopsy, and when should we be considering using one over the other?

Dr Amato: So, it really is not our decision. It's the pass lab. So, it's the technicians and the pathologists who read the biopsies need to be able to process a needle biopsy, which might be much smaller. Needle biopsies show to be fairly accurate in a lot of the hereditary disorders where you might just look for central nuclear core, and they might be- so, mainly in kids, but in the inflammatory myopathies, it's really patchy. So, if I'm thinking of an inflammatory, I like an open biopsy. I think it's hit and miss. And so, I like open biopsies for the adults that I'm thinking of inflammatory.

Dr Grouse: Do you have any other tips or tricks in the diagnosis of inflammatory myopathies that you could share with our listeners?

Dr Amato: I would say first, in terms of what muscle to biopsy, you're not doing them yourself, but you're referring to a surgeon. You have to tell them what to do with the biopsy. And you want to pick a muscle that's about an MRC grade 4 because if it's a normal muscle, the muscle strength, the biopsy, is likely to be normal. If it's less than a 4, you might just have end-stage muscle. And saying you can't tell end-stage muscle from a bad myositis, from a dystrophy, from a severe end-stage neurogenic. If I don't have a muscle that I would typically biopsy that's an MRC grade 4---for example, somebody with an early weakness and they’re only weak, say, in their in their hip girdle. So hip flexors, abductors, extensors, and we're usually not biopsying the iliopsoas or the gluteal muscles. Then what do you pick? That's when I like to do an EMG on one side of the body and look at proximal and distal muscles and select one that's irritable, you know, some fibs and positive sharp waves that I might biopsy. And then maybe consider doing a skeletal muscle MRI to go from muscle that's abnormal, that has a lot of edema in it, to increase the yield.

Dr Grouse: That's really helpful. And then, I think, jumping from that, what are pitfalls that you've seen neurologists fall into in this diagnosis or other challenging aspects of the diagnosis that you could review with us?

Dr Amato: Some of the things that we see are hard to pick up. It might be hard to pick up a rim vacuole. They're very rare, too. And so, you might miss it, particularly if you don't see a lot. Sometimes, like looking at the dermato and that's the, on the exam question, perifascicular atrophy, but that's a late stage, usually. And so, if you're really attuned and you're a good clinician, you make that diagnosis really quick. You do a biopsy, you might not see that paraphysical atrophy. So, they don't know that in a necrotizing myopathy, the pathologists often think of what they see in a toxic myopathy or a metabolic where there's a lot of necrotic fibers. But in most of the autoimmune necrotizing, it's not. It's actually what you see is more regenerating fibers, a few necrotic fibers. It's because it's usually been smoldering along for a while, and so you have many more regenerating fibers than ones that are actively, and that can fool a lot of people. So, that's a pitfall from that end of things. Some of these myositis specific antibodies aren't specific and at a low titer, particularly if you have more than one antibody being positive, that would be a red flag that it could be false. That's another pitfall. I think a lot of people don't, when they're examining people, really look at the finger flexors and stuff. And again, if I have somebody over the age of fifty, the most common muscle disease is IBM. Number two is IBM, number three is IBM. If you don't- and you have to think about that, and you need to examine the distal finger flexors because it doesn't get better with immunotherapy. You don't want to put people at the risk of immunotherapy when they're not going to get better. I talked a lot about the biopsies, and biopsy, biopsy, biopsy. But you know, sometimes you can make the diagnosis without a biopsy. So, if somebody's like a classic dermato rash and they have a dermato antibody, do they need a biopsy? No. If they have, you know, CKs of ten thousand proximal weakness, they're on a statin and they have HMGCR antibody, do they need us have a biopsy to confirm? Probably not.

Dr Grouse: Those are some really great pearls that you've shared with us, and I think will be very helpful to many of our listeners. Now, you mentioned earlier about the diminishing category of polymyositis as other types of myosidites have been discovered and better described. Do you think that is the most controversial aspect of this field currently, or are there other controversial areas or areas of ongoing debate that exist?

Dr Amato: It was very controversial twenty years ago, or maybe ten years ago. So, the rheumatology guidelines, they're the ones that are often saying, oh yeah, we were right. Polymyositis, it's just hodgepodge, and it's ever-shrinking. So that's not so controversial anymore. I mean, the controversies that we have, what's the pathogenesis of dermato? It's still a little debated, some- the old theory was that it was a complement-mediated microangiopathy and the damage was caused by ischemia. That's probably not the case. It looks more and more like it's a type 1 interferonopathy, and that's toxic to the vessels in the muscle. There's still a little bit of a debate about that or, you know, you have complement might be on it, but how much that might be damaging, or it's just a secondary phenomenon. I think in the antisynthetase things, I think there's some interesting things also with that these antibodies. We used to think of that they're just diagnostic biomarkers. But there's some recent studies suggesting that these antibodies which are directed against intracellular targets, which is interesting and applies to other autoimmune diseases and that are in the brain too. And we would think that, oh, if it's a intracellular target, it it's secondary. But there's suggestion now that- again, it did demonstrate that the antibodies actually get into muscle fibers. And they bind to these targets. So maybe they're just not epiphenomenon, but they might be binding to a target and causing pathology. And that's what there's some preliminary studies that are impressed, I will say, that have antibodies, anti-HMGCR, that actually go into the cell and they inhibit the enzyme. And that might be causing the pathology. And so that's interesting. And then IBM is a big field. Is this a primary autoimmune disease that has these other kinds of degenerative features like REM vacuoles, or is it a primary degenerative that has secondary inflammation, or is it a combination of both? So, that's probably the biggest controversy these days. It is probably with IBM. What the heck is causing it?

Dr Grouse: Sounds like a lot that we still have to understand about these diseases. This does lead me to wonder, though, have some of these new discoveries and ideas led to or will lead to any new breakthroughs, either in diagnostics or in therapeutics?

Dr Amato: So, certainly in therapeutics. So, the discovery of dermato being an interferonopathy, probably a beta-interferonopathy, has led to development of monoclonal antibodies that target interferon, and there's trials underway. And in phase 2 studies, I can tell you from talking to colleagues that participate just melted away the rash of dermato. So, I think that's going to be a very, very good drug in the future for dermato. There's others, like JAK. JAK inhibitors work on that interferon pathway too. So, I think we'll be going towards, like, less broad-spectrum steroids, IVIG, to going, let's go to the target. Certainly, in dermato, I mean, IBM, we don't know. There is an inflammatory cell that we see in IBM that has a receptor, KCRRN receptor, and there's a monoclonal antibody that targets that in IBM, and that's a phase 3 trial right now. Hopefully that study should be ending in December, and so early next year we'll have results about that. The fact that these antibodies might be pathogenic of themselves is other ways to get rid of the antibodies. So, getting rid of plasma cells and B cells, and FCRN receptors which have been approved or antagonists that are approved for myasthenia. Now CIDP might work in some of the inflammatory myopathies where we think the antibodies might be pathogenic. So, FCRN receptor antagonist and they're in trial now as well. And there's CAR-T therapies to knock out the antibody-producing lymphocytes and plasma cell. So, I think we're going to move into the field of individualized therapies as we find the distinct pathogenesis of these disorders.

Dr Grouse: That's really exciting to hear and I can't wait to see what's coming down the pipeline as more of these discoveries are made and the clinical trials advance. It has been such a pleasure. I've learned so much. So much is packed into the article. So again, I can't stress enough, please take the time to check out this article. I think you'll learn a lot, and it'll really help you fine-tune your diagnostic pathway in relation to myopathies.

Dr Amato: Oh, my pleasure. Thank you. Anybody has questions, please feel free to send me an email.

Dr Grouse: We may just take you up on that. Again, today I've been interviewing Dr Anthony Amato about his article on idiopathic inflammatory myopathies, which he wrote with Dr Kian Salajegheh. This article appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Be sure to check out Continuum Audio episodes from this and other issues, and thank you to our listeners for joining today.

Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.