Polymyalgia rheumatica was first described in 1966 in a case report. The condition has a wide range of symptoms and can be challenging to diagnose at times. As with most rheumatologic conditions, the exact cause isn't known. While there are no specific laboratory tests that establish a diagnosis, some tests are very useful. One of the most important features of polymyalgia rheumatica is its relationship with vasculitis and temporal arteritis. In this podcast, we discuss polymyalgia rheumatica with rheumatologists Cornelia M. Weyand, M.D., Ph.D. , and Kenneth J. Warrington, M.D. , from Mayo Clinic. We review the typical presenting symptoms, how to establish a diagnosis, helpful laboratory tests and management.
Rheumatologic problems are some of the most common health conditions we see as primary care professionals. They can become frustrating for both the provider and the patient, as in many cases it may take months and sometimes even years to establish a correct diagnosis. There are a variety of new tests available to help us confirm a diagnosis, as well as multiple new and effective treatment options. This episode is part of a seven-episode miniseries on Mayo Clinic talks dedicated to rheumatologic health problems to aid in the recognition, diagnosis, and treatment of your patients. Please find these additional episodes where you listen to podcasts or on CE.mail.edu. This is Mayo Clinic Talks, a curated weekly podcast for physicians and healthcare providers. I'm your host, Darrylhutka, a general internist at Mayo Clinic in Rochester, Minnesota. Polymyalgia rheumatica was first described in 1966 as a case report. It can have a wide range of symptoms and at times can be quite challenging to diagnose. And as with most rheumatologic disorders, the exact cause isn't known. There are no specific tests which exist to establish a diagnosis, but there are some that are quite useful. One of the most important features of polymyalgia rheumatica is its relationship with temporal arteritis, another rheumatologic condition which has potentially serious complications. Today, we'll discuss polymyalgia rheumatica with rheumatologist Dr. Connie Wyan and Dr. Kenneth Warrington, both from the Mayo Clinic. We'll review the typical presenting symptoms, how to establish a diagnosis, help for laboratory tests, and its management. You're listening to Mayo Clinic Talks. Connie and Ken, welcome and thank you for joining me today. As a geriatrician, I have seen a lot of patients with polymyalgia rheumatica, and what strikes me is the somewhat wide variety of presenting symptoms. So, let's start by asking you to describe the most common presenting symptoms of polymyalgia rheumatica. Sure, Darryl, uh, most patients come to us because of pain, and generally pain is localized to the neck, the shoulders, the upper arms. The hip area, upper thighs, but really the most prominent symptom in polymyalgia rheumatica is profound stiffness. And these patients have difficulty getting dressed in the morning, they have difficulty getting out of bed, and they feel unwell. So, in addition to these musculoskeletal symptoms, they have the constitutional symptoms of malaise, uh, they often may have a low-grade fever, their appetite is not so good. They may start to lose weight. So, very prominent musculoskeletal and constitutional symptoms would be most typical. Now, now, a few may have some swelling in the peripheral joints, that is less common, but that may be seen in the wrists, perhaps, or the knees. But again, the neck, shoulders, and hips would be the typical location for symptoms. OK. And I have seen several patients with the early symptoms of polymyalgia rheumatica, who have been misdiagnosed as fibromyalgia, and they can be somewhat similar. Are there other rheumatologic diseases that kind of mimic this? Well, as uh Ken has outlined, actually, the presenting symptoms of a polymyalgia patient are rather non-specific. These patients have pain. Most traumatic diseases have pain. They have stiffness. Well, the inflammatory arthrits have stiffness. So that is the big challenge of making a diagnosis of polymyalgia rheumatica. The diagnostic criteria that we use have low specificity. And I think for this reason, it is important that the diagnosing and managing physician are familiar with this condition that they can distinguish it from others. This can be difficult at times. Often we rely on such non-specific phenomena as, oh, that patient has responded very well. To low dose of corticosteroids. So that then becomes a diagnostic criteria how that patient responds to our therapy. And we'll get into testing a little bit later, but once a patient shows an elevated inflammatory marker, such as an elevated sedimentation rate, that pretty much rules out fibromyalgia, which doesn't really have that. Well, who's most likely to develop polymyalgia rheumatica? Are there risk factors for this? We see this mainly in older individuals, so the, the frequency of polymyalgia rheumatica does go up, peaking in the range of 70 to 80. So the average age would be somebody in their early 70s. It is thought to be pretty much exclusive to those over the age of 50, and, and women tend to be affected somewhat more frequently than men. The ratio is about 2 to 3 to 1. And really the highest frequencies that are seen globally tend to be in those who are either from Northern European countries or whose ancestors came from northern European countries. So Scandinavia generally has one of the highest frequencies of this disease, but in general, again, white populations of of Northern European descent. OK. Well, what's going on pathophysiologically in polymyalgia? If this is an inflammatory condition, but does it involve muscles? Does it involve joints, maybe both? What's going on? Well, the strongest risk factor for the disease, as already mentioned, is age. So only individuals that are older than 50, usually older than 70, are diagnosed with this condition. So it's actually pretty obvious that there must be age imposed changes that then lead to this condition. So our group has a particular interest in the phenomenon of immune aging, how the immune and inflammatory system ages. Interesting enough, as the immune system ages, it loses specificity in protecting us, but it gains this inflammatory activity. The term that has been coined for this is inflammaging. So the older individual is much more likely to have inflammatory activity. Why Because the bone marrow ages, and with aging of the bone marrow, the bone marrow is much more likely to generate myeloid cells with inflammatory potential. In patients with polymyalgia rheumatica, the output of myeloid cells with inflammatory potential from the bone marrow is higher. So we have to say the roots of this condition go into the bone marrow. An important other organ system is the liver because the bone marrow signals to the liver and induces what we call an acute phase response. And this is fortunately very useful for us because we can read that out. We can easily measure. Whether the liver makes an acute face response. The liver then starts producing certain proteins that we measure as CRP. Or as an elevated sedimentation rate, and the myeloid cells begin to make cytokines. So in a nutshell, polymyalgiaromitica is a condition associated with immune aging, with aging of the immune system, with bone marrow aging, with a shift in the bone marrow in producing certain cell subsets, and the propensity of the aging bone marrow. To release cells that cause inflammation. Well, I know the answer to this next question isn't really known, but are there thoughts as to what triggers this immune response? I mean, you, you start wondering because of the geographic distribution, could be some virus or possibility, uh, uh, other infectious agent. Uh, any ideas about what might trigger this? Well, if we go along with the concept that polymyalgia rheumatica is a disease of the aging immune system, then immediately comes to mind whether as we get older, our infectious exposures have been much wider. There's a new term appearing for this, the exposome. So just as we have a genome, we now have an exposome. The exposome uh broadens as we get older. When we are 70 years old, there are about 200 viruses that have established residency in our body, and our immune system tries to keep them under control. And makes constant slow smoldering immune responses against these viruses. So these viruses are very important in the process of immune aging. I'll give you one example. In the community of immune aging, cytomegalovirus is now recognized as one of the drivers of immune aging. So, is there behind all of this, an infection? I think the possibility is there. Is there a defined infection? I think that is unlikely. At least we have not seen that one. Microbial pathogen that we could identify as the inducer and driver of PMR. OK. Let's talk now about establishing a diagnosis in a patient. Are there any helpful physical exam findings? Right, yeah, with a, a condition like polymyalgia rheumatica where we still don't have a specific diagnostic test, right? So the history and physical are so essential in, in establishing a diagnosis and trying to separate this from its mimics. And so, first, we're looking carefully at the musculoskeletal system. Patients often will have difficulty with passive and active range of motion. In the neck, in the shoulders, you're going to have difficulty with a deduction of the arms and and arm elevation. There's going to be pain with range of motion of the hips. Generally, the peripheral joints, so the hands, wrists, knees, and ankles are going to be fairly unremarkable. There may be a subset of patients who may have some swelling in the peripheral joints. But on the other hand, if we do see prominent uh inflammation in the small joints, say, of the hands and feet, that would make us lean more towards perhaps an elderly onset rheumatoid arthritis type picture. So, we want to carefully look at the musculoskeletal exam, but then we also want to conduct a careful vascular exam. Because of the association, as you mentioned, Darryl, with giant cell arthritis, we have to be mindful to look for any physical exam findings, such as tenderness over the temporal arteries, loss of the temporal artery pulse, pulses in the extremities, we may check blood pressures. In both arms to look for symmetry. And so again, even though we're focusing on the musculoskeletal exam, we do wanna do a careful vascular exam, keeping in mind the uh the propensity of these individuals to have concomitant arerittis. OK. So there's somewhat soft physical findings, but nothing like, uh, you know, rheumatoid arthritis or even osteoarthritis. So let's say we have a patient in our office and we're considering polymyalgia rheumatica. The history is so important in this condition. What important questions should we be asking our patient? Well, you want to know about the daily cycle. You want to know when the pain and the stiffness is most pronounced because it is typical for this type of um myalgia and stiffness to be most pronounced in the morning. So to have early morning pain and stiffness that then eases over the day very important to know and separating it from other muscular skeletal conditions that are more degenerative in nature which have a tendency to be more pronounced as the day goes along and these patients will give you a typical description of how difficult it is for them to get out of bed. You know, to use the toilet because they can't stand up. As the day goes along, their symptoms ease. That's a very important piece of information to acquire. We do ask our patients about family history. And where their roots go if they go to Northern Europe, uh, that does at a point of suspicion because this is a Viking disease. The Vikings, you know, had this disease. They have it in the highest incidence and prevalence. So I think that is an important piece. We also ask about Other diagnosis in other family members of polymyalgia or of temporal arthritis, and we do ask about family history of rheumatoid arthritis because the two diseases cluster in the same family but not in the same individual. Connie, I did not know this was a disease that the Vikings had. This is a Viking disease and And maybe that's why they can't get to the Super Bowl, who knows. So we do ask our patients, you know, uh, and this of course has also brought much of the expertise. To the Mayo Clinic because as you know, we live in Viking land. When the Norwegians, Swedes, Danes, and the Finns came to North America, they settled right here in the middle. We take care of these patients. They have whole family clans that are affected by this disease. So, history is very important. History very important. Physical exam, maybe a little bit. What about lab tests? I know there's not any specific tests that say, yep, this is polymyalgia, but there are some important ones. What should we be ordering? While the CRP, the C-reactive protein, and the sedimentation rate are a must. We should caution that they are not always very elevated in these patients. So having a only borderline elevated sedimentation rate and CRP does not exclude the diagnosis, and the physician and patient need to stay aware of that. We do recommend that these patients have a rheumatoid, an anti-CCP antibody and a rheumatoid factor being tested more for exclusion reasons to fish out the patients that have, as I said, all the onset rheumatoid arthritis. And so the autoantibodies really serve as to separate PMR from other autoimmune diseases. The patients I have seen with polymyalgia rheumatica have had modest elevations of the sedimentation rate, as you mentioned. Is it unusual to see ESRs quite high, like over 100? Do you see that with this? If we see a set rate that has 3 digits, as we call it, we immediately have very high suspicion to say we need to rule out that this patient has frank vasculitis, has made the transition from polymyalgiamitica into frank vasculitis. So that would be a red flag. It is unusual for a PMR only patient to see these sky high sedimentation rate in ERPs, but again, it's a very helpful hint to see that there is activation of that system of this acute phase response. That the liver is responding to the bone marrow, and at the cytokine that sits in the middle is interleukin 6, that's the messenger between the bone marrow and the liver. We described that here in the early 90s that patients with polymyalgia rheumatica and chance cell arthritis have a distinct elevation of IELTS 6. We do actually recommend to capture that through CRP and sedimentation rate. It is unlikely to see a highly elevated IL-6 in the absence of an elevated CRP. So these two markers are very tightly correlated. OK. Well, since you mentioned the association with polymyalgia, rheumatica and vasculitis, temporal arteritiss, let's let's go into that just a little bit more. What is the relationship? How many patients with polymyalgia rheumatica also have temporal arteritiss? Yeah, I think that's a subject of, of ongoing investigation, actually. And I think I, I would start by making the case that we are very good as clinicians to ask about symptoms of giant cellarerritis. So, we're seeing a patient with PMR and we're asking about the typical cranial symptoms, headache, scalp tenderness, jaw claudication, vision disturbances. But we also need to keep in mind that there are some patients who have what we call occult vasculitis, meaning that it may not be producing symptoms, and those are patients who have aortic inflammation, and who have inflammation in the major branches of the aorta. And so there we have to keep a heightened clinical suspicion, like you mentioned, perhaps somebody with markedly elevated inflammatory markers or a patient who has had an incomplete response to treatment. Even if there are no cranial symptoms, we still need to have a heightened awareness and investigate the possibility that the patient may have aoritis or what we now call large vessel GCA and that is where imaging can be helpful in defining a diagnosis of vasculitis. And let me get into that just a little bit more. So, investigating for vasculitis, you would need some additional clues. In addition to just the basic symptoms of polymyalgia rheumatica at extremely high sed rate or something else that would suggest there's more going on, right? Well, we do always warn our patients. I have a case of a patient who was diagnosed with polymyalgia rheumatica, was treated for a year, was then treatment completed, and she went on a cruise into the Indian Ocean. And on the cruise ship lost vision on an eye, and the ship's doctor was not familiar with this association, and the captain actually was taking the ship to a nearby island where she was seen by a physician who recommended that she should be putting warm compresses on the eye. By the time she arrived back in the US, she had lost vision on the second eye. Oh dear. So, I always tell my patients with a PMR, Listen, this is a cousin disease of uh vasculitis. You need to be aware of that. You need to be alerted to that. Should you develop any visual symptoms, we want to respond immediately and promptly. I also recommend that they, if they travel and go on cruises into the Indian Ocean, that they travel with corticosteroids. So, let's say we have a patient, we've established a diagnosis of polymyals rheumatica. We're not suspicious for any vasculitis. How do we treat that patient? Yeah, so, uh, steroids, prednisone, has been the gold standard treatment, right, for, for decades, and patients typically respond quite promptly. The recommended dosage is somewhere in the range of 15 to 20 mg of prednisone once daily, and we generally maintain that dose for at least 2 to 4 weeks before we would consider tapering. Now, again, Classically, patients will respond, oftentimes within a couple of days with a dramatic relief of their symptoms. In some patients, the response may be a little slower and may take perhaps a few weeks for them to achieve a full clinical response. And again, the, the response to prednisone, as Connie alluded to, really is one of the confirmatory tests, so to speak, that this is indeed polymyalgia rheumatica, because if the patient is not responding as we would expect, that certainly raises our concern that we may be dealing with a PMR mimic, either an underlying vasculitis or another condition that uh may present somewhat similar to PMR and rarely, Again, especially in the context of somebody who is not responding to treatment as as we would expect, we want to then expand. Our diagnostic testing, we want to even include the possibility, although rare, that the person may have a perineoplastic type syndrome, but again, we're we're talking, you know, that small subset of patients who is not responding as expected. Yeah, I think we should emphasize that some of the patients I've seen are such so dramatically improved, often by the next day, that it's it's often a quite kind of a confirmatory test if that's what you're dealing with. So, we're tapering off the steroids. What about the patient who gets down to maybe 6 7 mg a day and drops down to 5, and all of a sudden their symptoms come back? Do you see that often? Yes, we need to be prepared for that. We do not yet have a curative intervention for this disease, so what we are doing right now is really that we are managing this overshooting activity of the patient's immune system and inflammatory system. So we go slowly. We need to give the system a chance to adapt. We need to be cognizant of the point that when we bring the prednisone down, the corticosteroids, that then the patient's adrenal glands need to be kicking back in and make, you know, natural cortisone for them again. So they can have a little hurdle. Around the doses going from 8 to 7 to 6 in that region because that's kind of uh the transition point between exogenous corticosteroids versus endogenous corticosteroids. Some patients will just do well by a slight increase in the dose and then try again to taper. We always try to minimize corticosteroids. It can be at times, OK, let's try to taper. That didn't work. Let's try to go up. But I think a mistake we should not make is to jump up to high doses of corticosteroids. These patients do not need 20 or 30 mg. 1 or 2 mg can do a lot for these patients, and so it's a bit of an art to taper down the steroids. I know there's a great deal of variability in this, but what's the typical duration that a patient may be on steroids? Any thoughts? It tends to be lengthy, um, and I, and I think, you know, as we're tapering the prednisone, we also need to be mindful that sometimes there may be multifactorial etiologies for the patient's symptoms. So I think we need to be on the lookout. Have they developed osteoarthritis of the shoulder or the hip joint? Have they developed rotator cuff tendinopathy, especially if symptoms are unilateral. So I think we have to, you know, constantly keep the differential diagnosis in mind, but we do know from epidemiology studies that patients often will linger with. Small doses of prednisone, sometimes for 23 years and rarely longer. So, of course, this has been an ongoing area of investigation, right? To identify glucocorticoid sparing therapies. And for the most part, really we have not identified effective agents until recently, there's been interest in evaluating a biologic therapy antibody blocking the action of interleukin 6, so anti-cytokine therapy. So this is now a subject of ongoing investigation. Uh, as you may have heard, there is the first FDA approved glucocorticoid sparing agent for PMR. It's an IL-6 blocker, where it was shown that in patients, again, in a subset of patients who have refractory relapsing disease, this agent has some glucocorticoid sparing properties. So I think this is an emerging area and we will gain more experience with this drug in the near future. OK? Well, Connie and Ken, you've given us some really interesting information about this fascinating disease, polymyalgia rheumatica. Can you give maybe 2 or 3 key points which summarizes our discussion? Well, I think that we need to keep in mind that the diagnostic criteria we use have low specificity. Having an elevated sedimentation rate, having pain in the shoulders and in the hips, being stiff in the morning, that's not an unusual thing for individuals that are older than 70 years of age. We need to keep that in mind. We need to keep in mind that there are probably a considerable number of false positives. That are diagnosed with polymyalgia or rheumatica, but there is another process. I should mention here that with the increasing use of checkpoint inhibitors, we're now seeing patients that are being treated for cancer with checkpoint inhibitors. And they can present with PMR-like symptoms, very typical. So we'll probably see in the future more of such patients than the ones that have PMR spontaneously. I think that's an important point. The second important point is we have no cure yet. So, we are not capable of bringing that patient quote into remission, but our ability to manage this disease is excellent. Most of our patients will respond very well. To a moderate dose of corticosteroids and we are able to take them away after 23 years and uh the patient has an excellent prognosis. And we need to keep in mind that this is a cousin of large vessel vasculitis, temporal arthritis, chances of arthritis. So there's always the possibility that the patient has occult vasculitis. That the patient transitions into vasculitis as a time goes on, and that we need to be aware of because these patients need our attention and need to be protected from severe manifestations of vasculitis. And lastly, I might add, we also need to be mindful of the adverse effects of chronic glucocorticoid therapy, right? So we want to be mindful about the individual's bone health and other long-term glucocorticoid consequences. Very good point. We've been discussing polymyalgia rheumatica with doctors Connie Wyan and Kenneth Warrington, both from the Mayo Clinic. Connie, Ken, thank you both so much for sharing your knowledge with us today. You can now listen to over 100 different medical topics developed for primary care providers on Mayo Clinic Talks podcasts. Find them at c.mao.edu or your favorite podcasting app. If you've enjoyed Mayo Clinic Talks podcasts, please follow us. Stay healthy and see you next week.
