Temporal arteritis is an inflammatory rheumatologic disorder that typically occurs in those over the age of 50. It can have devastating complications including loss of vision and stroke. It can have various presentations and can be challenging to diagnose at times. It also has an interesting relationship with polymyalgia rheumatica. Although there are abnormal lab test results associated with temporal arteritis, there is no one diagnostic test. A temporal artery biopsy is performed to establish a definitive diagnosis. Our topic for this podcast is temporal arteritis and our guests include Cornelia M. Weyand, M.D., Ph.D. , and Kenneth J. Warrington, M.D. , both from Mayo Clinic Rheumatology. We discuss the typical symptoms of temporal arteritis, its potential complications, how to make a diagnosis and treatment.
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, Darryl Chetka, a general internist at Mayo Clinic in Rochester, Minnesota. Temporal arthritis is an inflammatory rheumatologic disorder that typically occurs in those in their middle ages and the elderly. It can have devastating complications, including loss of vision, and at times can be quite challenging to diagnose. It also has an interesting relationship with polymyalgia rheumatica. Although there are some abnormal lab tests associated with temporal arteritiss, there is no one diagnostic test. Historically, a temporal artery biopsy has been used to establish a definitive diagnosis. Our topic for today's podcast is temporal arteritiss, and our guests include Doctor Cornelia Wyan and Doctor Kenneth Warrington, both from the division of Rheumatology at the Mayo Clinic. We'll discuss the typical symptoms of temporal arteritiss, its potential complications, and how to make a diagnosis and manage it. You're listening to Mayo Clinic Talks. Cornelia, Ken, thank you for joining me again. We had a nice discussion with polymyalgia rheumatica and we're gonna take part two now. As a geriatrician, I have seen a fair number of patients with temporal arthritis, and one thing that stands out in my mind is the various ways it has presented. So, let's start, I'm gonna ask you to describe the typical presenting symptoms of temporal arteritiss. Thank you, Darryl. Right, so patients may present in different ways, but really the classic symptom and perhaps the most frequent, is a new headache. Now, again, classically, patients may describe a headache in the temporal areas. There may be associated tenderness. They may see swelling actually of the temporal arteries, again in the temporal area, but then some patients may have a headache that is more generalized or maybe parts of the head that are not necessarily the temporal area. But that scalp sensitivity, that swelling over the arteries may be another feature. One of the more worrisome symptoms of the disease would be changes in vision. So patients may have either transient or temporary loss of vision. I may describe a curtain coming down over their field of vision in in one or or other eye, and then, of course, some patients, unfortunately, very abruptly lose vision, and this is often painless and again can be quite sudden now. We want to recognize this early because if there is vision loss in one eye, that could very quickly then spread to the other eye and of course, result, unfortunately in blindness. Another symptom that patients may describe is jaw claudication. This is a fatigueability and aching of the muscles, the chewing muscles, the muscles of mastication. And these symptoms come on again with chewing, they improve when the patient stops chewing. But really, then quite a few patients come in with fairly non-specific symptoms, so some may just feel unwell. They may start to lose weight, their appetite is down, they may have some low grade fevers, as we talked last time, some patients will have polymyalgia symptoms. So these are the more common presentations. Rarely, patients may come in because they have pain with the use of an arm, or they're exerting their arms, one side or the other, and they may develop this fatigue ability and pain that improves with rest. Yeah. And because these symptoms are so variable and sometimes pretty vague, I imagine that some patients can take a while before a diagnosis has been established, sometimes maybe months even. Is that, is that the case? That's definitely the case, but we have to say that we get them within a couple of weeks and months. To make a diagnosis as opposed to other autoimmune diseases where it could take us years because these patients are so sick. The average GCA patient is sick. They are not like, oh, I can live with this for the next 2 years. These symptoms impose a certain urgency. And because of the potential complications, and we'll get into those a little bit later, urgent treatment is really important for this condition. So what blood vessels are there than the other than the temporal arteries are involved in this or could be involved? Actually, here a little historical note may be informative. The first temporal artery biopsy in the world was conducted in Rochester, Minnesota, and it involved a temporal artery biopsy going from the ear to the top of the head, and it led to the recognition that this disease is a vasculitis. And the belief of Doctor Horton, who was that a physician who did the biopsy, was that removing the inflamed blood vessel would take care of the disease. In Rochester, we learned that there are other blood vessels involved, that the disease is almost never entirely confined to the temporal artery, that particularly the aorta is a place where the disease likes to go, that patients develop. Aortitis or can already outlined because the branches of the aorta are affected. This leads to ischemia in the arms. The top arteries that are targeted by giant cell arthritis is of course the extracranial branches of the carotid, including the temporal artery and the Arteriophthalmicca, followed by the aorta. Followed by the distal subclavian and proximal axillary arteries, we also have on the target list the vertebral artery, an attack of the immune system to the vertebral artery leads to ischemia in the posterior brain. And these patients present with a stroke. So when the rheumatologist in Rochester, Minnesota realized that the disease was not just going to the temporal artery, they suggested to rename it into giant cell arthritis, and that's actually the term that we use most today. So go into that a little bit and tell me about the giant cell part of this. That's seen pathologically. So what are you seeing when you're looking at this microscopically? So about 50% of patients have in the tissue lesion, multinucleated macrophages, beautiful giant cells. These multinucleated macrophages appear because macrophages in the tissue come under genotoxic stress, and they duplicate the nuclei, but they are not able to duplicate the cell, so they accumulate all of these nuclei. As I said, about 50% of the patients have a multinucleated giant cell, both in the temporal artery biopsy. Let's talk about the relationship between temporal arteritis and polymyalgia rheumatica. How do those two go together? Yeah, as as we talked last time with polymyalgia rheumatica, there is a close relationship between GCA and PMR and some even believe that they may be two ends of the same disease spectrum, so they're closely linked. We generally see about 40 to 50% or so of patients with GCA who have polymyalgia symptoms. This is at disease diagnosis. Now, of course, once we start to treat GCA then Oftentimes, the polymyalgia symptoms will rapidly diminish and disappear, but oftentimes then when we see relapses of the disease, when we see relapses of giant cell arteritis, it is often those PMR symptoms that return and clue us in to the fact that the patient is relapsing and often they have elevated inflammatory markers and so forth. I know there's a wide variety of presentations of this, but do patients who have both conditions typically develop the polymyalgia first and then go on to have symptoms of temporal arteritis, or do they, do they both typically come on at the same time? Great question. Yeah, they often come on concurrently, but there is a subset of patients who initially has polymyalgia symptoms, and if we counsel these patients carefully about the symptoms to watch for. And because they may develop giant cell arteritiss later in the course of the disease, and sometimes it can be subtle. And so, as we discussed, if a patient with polymyalgia rheumatica is not responding to treatment as we would have predicted, then we have a heightened awareness and we very carefully. Evaluate them for the concurrent presence of giant cellarerittis. Ken, I think you mentioned that about 40 to 50% of patients with temporal arteritiss also have polymyalgia rheumatica. How many with polymyalgia rheumatica also have temporal arteritiss? Tricky question, and it depends a little bit on how hard you look, right? Typically, we'd say maybe 20% or so of people with PMR have concomitant GCA but then some of the research data suggests that it's probably at least 30%, if not higher. In other words, if you obtain careful imaging of individuals with polymyalgia rhematica, either. that MRI and geography or PET scan really to understand, is there a kind of subclinical inflammation in the arteries, then you see it more frequently. And Doctor Win actually has done immunologic studies demonstrating that even in the absence of overt clinical giant cellarerittis, you may see immunologic signs of inflammation in the arteries and, and perhaps you'd like to speak about that. Well, that's one of the most interesting questions in this disease. We now look at the polymyalgia rheumatica as a predeceased to China cell arthritis. It occurs in the prephase, and as Ken already said, there are patients who have PMR before. They are being diagnosed. They have PMR when they are being diagnosed. There are patients that develop PMR after they have been diagnosed. And PMR follows the entire trajectory of this vasculitis. We have looked for so-called immuno phenotypes. So, are there signs and signatures in the immune system of the patient? That are present in the polymyalgia patient and that are shared with the vasculitis patient and then taking the next step, can we actually utilize understanding of these immune phenotypes to predict who will make the transition. From polymyalgiatica to full-blown China cell arthritis. We've talked a little bit about the complications of temporal arterittis, blindness being the most commonly uh known one, but you mentioned this is really more of a systemic vasculitis. So what else can happen? Well, the feared complications are fourfold, um, blindness, stroke, aortic arch syndrome, and aortitis. So this relates to the different vascular territory the disease can go to. Does it lead to a stroke in the eye? Blindness is a stroke in the eye. Does it lead to a stroke in the posterior brain? Does it occlude larger blood vessels in the arms and leads to aortic arch syndrome pulseless disease? And does it lead to aoritis? I think the fact that the disease is so long lasting and that we now understand that it persists over decades. Has made the aorta the major organ of interest. We know that most of our patients have aortitis. We know that most of our patients persist to have aortatis to a lower or to a more intense degree, and obviously that is a late complication of the disease that these patients need a surgeon to repair the aorta. Well, let's talk about establishing a diagnosis. You've already mentioned how important the history is in at least getting us to suspect temporal arteritis. Is there anything helpful on physical exam? Absolutely. And as we mentioned with patients often coming in with cranial symptoms, the first area that we want to examine carefully is the uh temporal arteries. So we're looking whether there are signs of swelling. Is there tenderness, and then is there loss of pulsation of the temporal artery. So sometimes we get questions, somebody has sort of a bounding prominent pulse. Well, that's less worrisome than somebody who loses their temporal artery pulse because the uh inflammatory lesion in the vessel is going to result in occlusive disease and so the pulse may be diminished or lost. So, those are the common things, tenderness, swelling, and loss of pulsation. But then, as we uh discussed, it's a systemic disease. So could there be involvement of the aortic arch arteries? So, we wanna make sure that we're assessing the bilateral radial pulses, the bilateral pedal pulses. We typically measure blood pressures in both arms to see if there is a significant discrepancy in those blood pressures that might indicate Arterial occlusive disease in the in the subclavian and axillary arteries, which can be a complication of giant cell arteritis. And then in those patients who have the concomitant polymyalgia, we would elicit the signs of pain and inflammation with range of motion of the shoulders, the hips, the neck and spine. So how about laboratory tests? I know there's not one specific test that's positive for temporal arthritis, but what should we be ordering? Well, because these patients have such an intense inflammatory syndrome, we are going to look for inflammation. The inflammation that we can most easily detect. is an inflammation that involves an acute phase response from the liver, and we measure that in the laboratory by elevated CRP values and elevated sedimentation rates and because the inflammation is intense in the typical patient, we will see impressive elevations of CRP and sedimentation rates. That part of the laboratory testing does of course not tell us what is truly going on in the blood vessel wall. For that we need more sophisticated testing approaches, particularly imaging approaches and the biopsy. It It has been helpful to dissect the view of this disease into what is extravascular disease and what is vascular disease. The extravascular disease we capture by laboratory testing, the vascular disease we capture by biopsy and imaging. Now, my understanding is that the inflammatory tests, sedimentation rate, and so forth are markedly elevated, often over 100. Is that typical? The so-called 3 digit sedimentation rate, that is red flag, we have to go and look, does this patient have giant cell arthritis? No, we have educated generations now of residents and fellows that this should trigger a referral to rheumatology to look for that. There are other helpful indicators because this acute phase response of the liver leads to anemia. Elevation of platelets, elevation of firinogen, and all of the inflammatory proteins that the liver makes. These can help in completing that assessment. I recall a patient I had years ago who had classic symptoms of temporal arteritiss, and she actually went on to have a positive temporal artery biopsy, but she had a normal sedimentation rate. That must be pretty uncommon. Not as uncommon as we may be thought. So as already mentioned, the disease switches, uh, having its preferential tac area on the head, extracranial arteries, and then goes to the aorta. If you look at aortic patients, they often have normal sedimentation rate and normal CRPs. So, led by Dr. Warrington, we have analyzed the inflammatory nature of aoritis in 25. Patients that had surgery here in Rochester and all 25 patients had a pretty normal sedimentation rate in CRP. Mm, interesting. So, physicians need to be aware of that fact. Yeah. How about imaging studies? Any indicated in temporal arteritis? Yeah, there, there is a growing interest in the use of imaging studies as a, as a non-invasive means of diagnosing the disease. So imaging really has two roles in giant cell arteritiss. One is, could it help us establish a diagnosis, and the other is imaging is important to evaluate the extent of the disease. As we said, being a systemic disease, we want to know is there aoritis. So for the first aspect, can it help us with diagnosis in Many ways, yes. So there is increasing interest in the use of ultrasound, ultrasound of the temporal arteries that can show presence of swelling in the wall, so thickening may show narrowing and decreased flow in the vessel, that would be indicative of vasculitis. Now, again, one would want to make sure that this is performed in a center that has experience and expertise with this technique, because it can be somewhat subtle and Maybe difficult to interpret, but there is a growing use of ultrasound for the cranial arteries. But then again, we use imaging, CT angiography, MR angiography most often to evaluate for the presence of aoritis. And this is now reflected even in the American College of Rheumatology guidelines. So the ACR guidelines recommend that if there is a strong suspicion for GCA and the biopsy is negative, we should obtain. imaging to help us secure a diagnosis. If we have made a diagnosis of GCA we still want to obtain imaging to evaluate for the presence of large vessel disease to really appreciate the extent of the disease, mainly is there aoritis because patients with aoritis may be at risk, may be at higher risk of aortic complications down the road. So it really is fascinating area that is changing fairly rapidly. Let's talk about temporal artery biopsies, because these have been historically done to establish a diagnosis. How do you approach this? How do you start? You got two temporal arteries. How do you start ordering a temporal artery biopsy? In tertiary centers like Mayo, we will have networks of physicians that take care of such patients, so we have immediate access to temporal artery biopsies through our colleagues in ophthalmology who offer us very fast temporal artery biopsy within days. So to avoid ambiguity about the question, is it important whether the patient had corticosteroids or not, the temporal artery biopsy remains our major diagnostic procedure, and we have seen a trend recently. To make a diagnosis based on clinical criteria, obviously that comes with a risk, clinical criteria being older than 50 years. Having a headache and having an elevated sedimentation rate amongst the 150 million Americans who qualify by age, there are sufficient numbers of individuals who have a headache and have an elevated sedimentation rate. The danger of a clinical diagnosis is that it's really false positive. And here the biopsy is the most powerful instrument we have. Nothing is as powerful as having a biopsy. There have been discussions whether the negative biopsies are false negative. You know, there is evidence that a positive or that we capture 92% of patients with a biopsy. We capture another few% of patients with a second sight biopsy. But as you hear from these numbers, biopsies are really important diagnostic procedures that allow us to say whether our patient has vasculitis or not. There's only a small group of individuals that will have a negative biopsy yet has vasculitis. If you biopsy one side and it's negative, do you biopsy the other side? We used to recommend to go from one side to the next. That has changed somewhat. It has changed because the life expectancy of our patients has extended. And we now have a tendency to spare the second side for the future because that patient may come back to us in 15 or 20 years with clinical presentation that is suspicious and then it is nice to have the second sight. To do a biopsy on. There are patients where the first biopsy is negative and where we do the second biopsy relatively soon after the first because there is just that lingering concern that there is vasculitis that we didn't capture. Let's talk about treatment. Still steroids? Well, steroids have been used, and again, the efficacy really established here at Mayo Clinic in the 1940s, when they recognized that prompt start of glucocorticoids could save people's vision, right? So that's really the emphasis on early disease recognition. While you're evaluating the patient, while you're waiting for tests and biopsy, if the suspicion is high enough, the patient should be started on glucocorticoids to prevent vision loss. Now, there is some subtleties in terms of dosing, for instance, if a patient comes in with symptoms of visual ischemia, we would often treat with a short course of intravenous. Methylprednisolone, generally 1 to 3 days of pulse dose methylprednisolone, but the majority of patients with giant cell arthritis, again, in the absence of visual ischemia, will receive approximately 1 mg per kilogram of oral prednisone daily. So, prednisone remains kind of the gold standard treatment for giant cell arthritis. We know very well now from multiple studies that the idea that the biopsy is going to turn negative with steroids is, is really a myth. If there is inflammation in the temporal artery, that inflammation is going to persist there for weeks and months, and so starting treatment is absolutely appropriate. Well, that should Emphasized actually, so we have conducted the so-called second sight biopsy here in Rochester where we made a diagnosis based on the first sight biopsy and then the patients were rebiopsied on the other side after 369, or 12 months. And the surprising but important take home message is that in the 1st 3 to 6 months, there are very few patients that turn from positive to negative on the second side. By 12 months, with full clinical treatment, half of the biopsies were still positive. So that gives you a good idea about the longevity of this disease. And raises the important question, is there such a thing as responders and non-responders to the standard therapy protocol that we apply? And could we fish out the responders and the non-responders to adapt to that categorization? But the second site biopsy showed unequivocally that GCA is a long standing. Chronic disease and we encourage patients to have a biopsy even if they have been on steroids for a couple of weeks because there is a good chance to capture the disease. One of the most challenging parts of managing temporal arteritiss is getting patients off their steroids. Seems like this can go on for a month, sometimes even years, and you're getting down to the tiny doses and even the 0.5 mg a day makes a difference in terms of like getting some symptoms back. How do we take care of that or is there a way to manage that any better? Yeah, that, that certainly is a challenge. Again, we recognize now the disease chronicity and the need for prolonged course of glucocorticoids. So, fortunately, there is a glucocorticoid sparing agent, so we now have one FDA approved biologic agent that targets interleukin 6. And it does allow a more rapid tapering of glucocorticoids. So, generally, you know, historically, we would treat patients for 1 to 2 years and sometimes longer. Now, with the additional use of an interleukin 6 inhibitor, in addition to glucocorticoids, we often try to taper the glucocorticoids over 6 months or so, but again, It is a chronic disease. There still is risk of disease relapses and the patients need to be monitored very carefully. Mhm. Well, Ken, Connie, you've given us some really interesting information about temporal arteritiss. Can you summarize our discussion maybe with two or three key points? Well, I think the most important take home message is that GCA is a chronic disease. That in many patients, if not in most, the disease will affect the aorta and that the aorta requires monitoring and adjustment. A second important message is that we have a research program built around this disease to answer these important questions of predictive biomarkers. Can we predict the course of the disease in patients, and what kind of chronic therapeutic interventions can be offered to our patients. To manage a disease over decades. That is important that word gets out because I think these are the most impressing clinical issues that our patients have. Well, as you mentioned, Mayo has a strong history of temporal arteritiss research and treatment, so we've seen a fair amount of this over the years. It's a Viking disease. Vikings brought it to Minnesota. Doesn't exist in Green Bay. Packers don't have it. It doesn't exist in Green Bay. No, OK. We've been discussing temporal arerritis with Doctor Cornelia Wyan and Doctor Kenneth Warrington, both from the Mayo Clinic. Ken Connie, thank you both so much for sharing your knowledge, uh, with this fascinating disease. Thank you. Thank you. 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