Thomas E. Lloyd, MD, PhD, is an Associate Professor in Neurology and Science at John Hopkins University School of Medicine, talking about the diagnosis and treatment of Inclusion Body Myositis.
Interview conducted by Ivanhoe Broadcast News in May 2017.
Inclusion Body Myositis is a condition that many of our viewers probably have not heard of. Can you give me a quick overview of what is it and what does it impact?
Dr. Lloyd: Inclusion Body Myositis is a rare disease usually affecting adults over the age of fifty. It will start off with extremely slowly progressive weakness. There is often difficulty walking and difficulty standing up from a chair. It will often affect muscles controlling the hands, and a patient will develop grip weakness. Half of patients will develop problems swallowing as well. Frequently, since it starts in older adulthood, people are told you’re just getting older; you’re not as active as you used to be and you’re not exercising enough. Because of that, there is typically a five or more year lag between onset of symptoms and actual diagnosis.
How frustrating is it for your patients to know that something isn’t right but nobody can really put a finger on it. Is that the situation a lot of these patients?
Dr. Lloyd: An individual patient will often see their primary care doctor multiple times before a blood test or a muscle biopsy shows that there is, in fact, something wrong. Also, patients will often be misdiagnosed with polymyositis and treated with steroids or other immunosuppressive medications with toxic side effects that are ineffective.
You have these symptoms that may be slow, and some of them may be very vague. How do you actually come to the diagnosis that this is IBM?
Dr. Lloyd: Usually something is found once someone checks the blood test where an increase in what’s called CK is seen. It’s one of our muscle enzymes and usually, but not always, muscle enzyme levels are elevated in the blood in IBM. Normally, that will lead to a muscle biopsy. In most cases an underlying diagnosis of IBM is made on muscle biopsy.
You mentioned these symptoms, such as the weakness, the difficulty getting up from a chair, the trouble swallowing. Is this a condition that is often confused with neuromuscular or other conditions?
Dr. Lloyd: It is. ALS is really what a lot of patients are initially worried about. If they are on the internet and then see progressive weakness and problems swallowing; ALS is one of their major concerns. Usually a muscle biopsy is able to distinguish between ALS and IBM, and most other similar diseases.
In what ways is IBM like ALS and in what ways is it really its own animal?
Dr. Lloyd: It’s similar in that it often affects one side of the body first, so it might only affect say the left arm or left leg initially. It’s also similar in that swallowing is often affected. In both cases we see that they are gradually progressive and don’t respond to any known treatment. The major difference is that ALS is usually much more rapidly progressive and it affects the motor neurons in the spinal cord and in the brain; whereas in IBM it’s a muscle degenerative disease. On testing for example, using what’s called an EMG / nerve conduction study and also a muscle biopsy, usually you’re able to see the characteristic muscle pathology of IBM.
Is this disease something that people die from?
Dr. Lloyd: That’s somewhat controversial. There are large studies where they have looked at IBM patients and really tried to define whether or not IBM increases mortality. When I say large, it’s large for IBM but it’s only maybe a hundred patients. It isn’t really clear that IBM patients do in fact die at a younger age than others. That said, many of us who see a lot of IBM patients and follow patients in the late stages note that some develop such severe problems swallowing that they will either not be able to eat and take adequate nutrition or even aspirate. This can lead to aspiration pneumonia and occasionally that can be fatal. It’s different from ALS, and ALS is usually described as invariably fatal, usually within three to five years. With IBM there are certainly patients that live with this disease for thirty to fifty years. It goes back to what you were asking about earlier in terms of differences between IBM and ALS. ALS often affects your breathing very early. In order for an ALS patient to live beyond five years you normally will have to have a ventilator. Whereas in IBM, we think breathing is affected very late in disease, and usually it’s not that severe.
What are the treatments?
Dr. Lloyd: The number one treatment that we have found that works interestingly enough is exercise. Many patients are actually told by their primary care doctors that since you have a muscle disease and your muscle is breaking down that they should avoid exercise. That was sort of the old thinking that in Myositis, because the muscle is inflamed and breaking down; you should avoid exercise which can obviously break down muscle. But in fact, recent research studies have shown that certain types of exercise are beneficial.
What types would be best?
Dr. Lloyd: What we found is that low-impact, aerobic, endurance-type exercises are usually more beneficial than more high-impact exercises.
Do you have a recommendation of minutes for patients? Do you tell them to go out and do forty minutes a day?
Dr. Lloyd: The best regimen is variable; it really depends on the individual patient. All of our patients at our center see a physical therapist and occupational therapist. Their individualized exercise program is really based on what their level of endurance is and what their muscle strength and function is like.
Exercise being one of the prescriptions; is there anything else in terms of treatment?
Dr. Lloyd: Nothing has been proven. A number of clinical trials have been done with particular immunosuppressive drugs. Many of us think that there is a small subset of IBM patients that will benefit somewhat from immunosuppressive medications like IVIG or prednisone. However, when you look at large studies of prednisone or similar immunosuppressive drugs; on average actually patients do worse when they’re treated with immunosuppressive drugs because of side effects. And so in general, we recommend against immunosuppression.
Do you know the cause of IBM, why people develop this disease?
Dr. Lloyd: We don’t. We think that almost certainly there are underlying genetic risk factors. There is an increased risk in some families. When you look at the underlying genetics of the immune system, there are certain genetic variants more commonly seen in IBM. We think that there likely is an autoimmune trigger. What we don’t know is if this autoimmune trigger then leads to a degenerative cascade like in ALS or Alzheimer’s disease that even when you remove this autoimmune trigger, the muscle continues degenerating on its own, or if the immune response is really just refractory to all the immunosuppressive drugs that we’ve tried.
What’s on the horizon?
Dr. Lloyd: One of the most promising class of drugs actually increases your body’s own ability to generate muscle. We are just now completing a large multi-site international study on one such drug. Hopefully in the next six months or so we’ll know how beneficial that is. There are similar approaches using gene therapy designed to also stimulate your muscles own ability to regenerate.
Are you able to tell me what class that is or what kind you’re looking at?
Dr. Lloyd: They are known as Myostatin inhibitors. There are antibody inhibitors that bind to and inhibit Myostatin receptors. There are also small molecule inhibitors and in fact gene therapy approaches that will lead to a downregulation of one’s own Myostatin.
The name of this disease; where does it come from?
Dr. Lloyd: The inclusion bodies are seen under the microscope and it’s really what separates inclusion body myositis from other more common forms of Myositis, for example dermatomyositis and polymyositis in which similar inclusions are not seen.
And those forms of myositis also neuromuscular diseases as well?
Dr. Lloyd: Correct. Although in dermatomyositis and polymyositis, interestingly, the muscles affected are usually what we call proximal muscles in your upper arms involving raising your hands, and proximal legs. In inclusion body myositis it really has a unique preference for finger flexor muscles and quadriceps muscles.
This is in the muscular dystrophy family, it’s similar, and why is that?
Dr. Lloyd: It’s similar in that it’s a relentless, progressive, degenerative disease of muscle. Although usually it’s actually considered separately from classical muscular dystrophy in that we don’t really understand what causes it. Muscular dystrophy is by definition an inherited or genetic disease.
What do you say when you see patients that are newly diagnosed?
Dr. Lloyd: Probably the best resources are the Myositis Association (myositis.org), a very helpful patient support group. There are a lot of resources there for patients. Another very helpful patient group resource is the MDA, Muscular Dystrophy Association. Even though it’s not really a Muscular Dystrophy, it does fall under their umbrella of diseases that they support.
Is there hope for other kinds of therapy beyond exercise that would work?
Dr. Lloyd: Yes, I think so. I would say until the last few years, what you saw in IBM was one failed clinical trial after another, in terms of trying different immunosuppressive medication and drugs. Over the last five years, there’s been more of a focus towards stimulating regeneration and drugs designed to actually slow muscle breakdown. Hopefully with this new approach one or more of these drugs will show efficacy.
Is there anything you want to make sure people know?
Dr. Lloyd: Probably the most important thing for the public to know is that IBM is probably underdiagnosed, and that if you are over age 50 and gradually getting weaker and weaker to the point where you’re having difficulty walking or getting up out of a chair, what I’d like to emphasize is that it’s not a normal part of aging. There are simple tests that can be done to diagnose muscle disease, and doctors should refer patients who complain of progressive weakness to a neurologist or neuromuscular specialist.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
John Infanti
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here.
