Why Identifying and Managing Giant Cell Arteritis as an Emergency Is Crucial

Leonard Calabrese, DO, Paras Karmacharya, MD, MS, and Adam Kilian, MD, break down why giant cell arteritis (GCA) demands immediate action, explain how to confirm diagnosis quickly, and what same-day treatment options like upadacitinib (Rinvoq) mean for patient care.

Video Transcript:

Hi, this is Dr. Len Calabrese. I’m the Vice Chairman of Rheumatology at the Cleveland Clinic and the co-director of the Center for Vasculitis Care and Research. And I’m here today to talk about giant cell arteritis in clinical practice.

Hello everyone. I’m Paras Karmacharya. I’m a rheumatologist and a physician scientist at Vanderbilt University Medical Center, and today we’ll be talking about giant cell arthritis as a medical emergency and what we can do about it.

Hello, it’s great to be with you. I am Dr. Adam Killian. I am a rheumatologist and the director of the rheumatology fellowship training program at St. Louis University.

In the field of rheumatology, we take care of a lot of complex rheumatologic diseases, but there are relatively few medical emergencies. Giant cell arteritis is one of the most common when we see it, particularly when it presents with signs and symptoms of head and neck ischemia. As all rheumatologists know and neurologists and ophthalmologists, onset giant cell arteritis poses a risk for rapid and permanent visual loss. It is heartbreaking when it occurs, and unfortunately, even with our use of glucocorticoids for the past generation and now with steroid sparing agents, including tocilizumab, which has been around for a few years in the newest edition, Lapatinib based selective JAK1 inhibitor, an oral option visual loss is still seen in up to one out of five patients in some studies. So what is the risk scenario? Well, giant cell arteritis is the most common form of inflammatory arteritis of all the spectrum of vascular inflammatory diseases, and it’s a big disease.

It involves large vessels including those perfusing, the head and neck. And over the past 10, 15 years, we’ve learned a lot about large vessel involvement below the neck, the aorta and its branches in the presence of head and neck ischemia, patients presenting with previous visual symptoms, amaurosis, fu, diplopia, et cetera, or signs of ischemia to the muscles of the face, throat, and attendant tissues when patients develop things such as me. Back up for this, the vascular complications of giant cell arteritis involve the large vessels, those perfusing the head and neck, and in a surprisingly large number of patients, and recently supported by vascular imaging, large vessel involvement of the aorta in its branches in the presence of head and neck ischemia, which we learn about by signs and symptoms such as transient visual loss like ASOD or diplopia, or other forms of ocular ischemic symptoms or in the presence of jaw claudication, which patients don’t tell us about.

But this can be represented by pain on mastication, pain in the tongue, pain in the face. All of these are warning signs that visual symptom loss may be impending and thus represents a medical emergency. What do we do in those settings? Well, we certainly draw acute phase reactants, which are highly sensitive but not specific. And then we launch into some diagnostic algorithm where we either try to obtain a temporal artery biopsy, which is done very commonly in the United States or ultrasound or a sequence of these two. It depends upon where you are practicing and what resources are available to you. The most important aspect of giant cell arteritis and its treatment is that in the presence of visual symptoms or any sign of head, head and neck ischemia, if the pretest probability of this is high treatment should be initiated immediately. If there’s visual symptoms, patients are often hospitalized for high dose intravenous symptoms.

Most patients with head and neck ischemia are started on high dose prednisone, ways that we have been doing this for many years. But treatment first, securing the diagnosis is secondary and often delayed. Sometimes we may not actually have giant cell arteritis. We can back up and correct our diagnostic approach and our conclusions, but in the presence of these types of symptoms of head and neck ischemia visual symptoms, it is a true medical emergency and we have to treat sooner rather than later. Once we do this and initiate glucocorticoid therapy and secure the diagnosis, now we start thinking about long-term management and how we can best serve these patients to maximize efficiency of these therapies and to minimize their toxicities. Fortunately, in the past few years, we have had biologic options, including IL six inhibitors since about 2017 and this past year with the approval of the selective JAK one inhibitor upadacitinib an oral option that I believe that when the diagnosis is secured should be started sooner even on the same day as glucocorticoids if the algorithm and the diagnosis support it. So this vignette is really talking about giant cell arteritis as a medical emergency, how we should start therapy sooner, particularly when there is a risk of impending visual loss and about the advances in the availability of steroid sparing agents that we’ll talk more about in another video.

So despite being the most common vasculitis in adults over the age of 50 giant cell arthritis or A GCA is frequently delayed in diagnosis, but it’s not just a diagnostic challenge, it’s a vascular emergency. So one that can really lead to this permanent preventable disability. And so in this video, I want to walk you through the pathophysiology, how quickly and effectively we can confirm the diagnosis and how to approach the first few hours to days of management and how we can integrate some of the newer agents such as invoke not in isolation, but in the real world context of patient care. So let’s first talk about giant cell arthritis as a medical emergency. So giant cell arthritis affects medium and large size arteries with a strong predilection for extra cranial branches of the carotid artery. And so what’s happening under the hood is these Matic inflammation driven by dendritic cells, CD4+ and T cells, and there’s some macro activation and that ultimately leads to intimal hyperplasia, vessel wall remodeling, and ultimately that leads to this luminal narrowing.

So it’s not really just systemic inflammation, but it’s true vascular occlusion leading to ischemia. And as a result of that, the patients can have permanent vision loss, and this is something called anterior ischemic optic neuropathies or A ION central retinal artery occlusion or posterior ischemic optic neuropathy. Patients can also have strokes, often vertigo B, and they can have aortic inflammation leading to aneurysms or dissection in about 10 to 20% of the patients and sometimes years after the initial symptoms. And so it’s important to realize that this vision loss that happens as a consequence of this inflammation is often painless and sudden, and once it occurs, it’s often irreversible. If one eye is affected, the second IE follow within one to two days. So it’s very important to recognize it early. So in UK cohort, approximately 90% of the vision loss occurred before effective therapy was initiated, and the median time from symptom onset to treatment was about 21 days.

And largely this was due to non ocular symptoms being missed or misattributed. And so that is why we emphasize time is sight and time is brain. So the cornerstone of treatment for suspected GCA. So let’s talk about the treatment strategies now. And so when the vision is at risk, we have to immediately start glucocorticoids, and that is really the cornerstone of treatment in suspected GCS patients. Now, if there are ocular symptoms such as diplopia or what we call Amaurosis Fugax, which is transient loss of vision in one eye or blood vision or lost vision, we typically initiate IV methylprednisone in the doses 500 to a gram daily. So a thousand milligrams for three days, and this is followed by an oral chamber. Now, if IV access is delayed or it’s not unavailable for some reason, then we would not delay therapy because of that, we would start oral prednisone.

So typically 600 to a hundred milligram per day comes out to be around one milligram per kg per day. And if the patient has systemic symptoms without vision involvement, then we would start prednisone at 40 to 60 milligrams daily. And so this is one of those conditions in medicine where really the mandate is a little bit different. So treat first and then conform second. And that said, the diagnostic yield doesn’t vanish after a steroid initiation, so you can still get a temporal art biopsy, and that can be positive up to two weeks following steroid therapy and ultrasound To diagnose a patient can be positive for up to three to five days after therapy. And it’s also important to consider advanced imaging such as CTA or PET CT for large vessel disease. So there is time to work up, but not really time to delay therapy.

Now let’s talk about how we can confirm the diagnosis of GCA. And so there are a few strategies we need to keep in mind. We don’t want to overtreat GCA, but again, under diagnosing it has life altering consequences. So really diagnosis matters a lot. The recommendation is to take a parallel worker approach starting as soon as the treatment begins. And so when available, temporal artery biopsy is often my first diagnostic step. So the key is to look for something called a halo sign. And so this is a dark hypo echoic non-compressible ring around the vessel wall, and so it represents wall edema and inflammation. And sensitivity of this is around or ultrasound is about 77 to 88%, and specificity is around 95 to a hundred percent. So if you see it, it’s very specific, but if you don’t see any findings, it still could be GCA in the right setting.

So also important is that it’s done by a trained operator, and that does increase both the sensitivity and the specificity, and we are looking for a halo sign of greater than 0.7 millimeter, which is highly predictive. And then bilateral involvement improves specificity, and I would consider also scanning the auxiliary arteries, particularly in patients with systemic symptoms or those who have arm claudication. The sensitivity drops the longer you wait after a steroids, so important to consider that. But studies show some findings persist even up to seven to 10 days, but typically we would want to get it within two days of starting steroids. The other important part of workup is inflammatory markers. So the ESR and CRP and CRP is more sensitive than ESR, but important to remember that up to 4% of biopsy proven GCA patients have normal inflammatory markers. So while abnormal labs support the diagnosis, normal ones do not necessarily rule it out.

So always important to consider the clinical context and patient symptoms there. The other thing that we discussed is the temporal artery biopsy. So this is still a gold standard, especially where ultrasound might not be available. And then it is important to get some of the specifics of the biopsy, right? So we need at least two centimeters segment because we can have skip lesion, patients can have skip lesions. And then it is important to recognize that bilateral biopsy increases the diagnosis yield. So again, due to that skip lesion pattern that we see in GCA and the diagnostic yield remains decent up to 14 days after steroids, although the sensitivity does decline over time. And then the next modality to consider is CTA, so CT of the chest, abdomen, and the pelvis, or sometimes we consider a pet ct. And this is done in patients with suspected large vessel involvement, ARM claudication constitutional symptoms without cranial science, or simply when the clinical picture doesn’t fit classic GCA, then these are modalities to consider.

And so these can detect neural inflammation in the aorta and its branch vessels important not only for diagnosis but for long-term surveillance. Since GCA related ATO IES can develop really insidiously and they can lead to aneurysms and dissection is not detected timely. Now let’s sort of move on to therapies beyond steroids. So I think the role of steroids spearing agents is very important to consider, especially in select patients. And once the acute threat is stabilized, our job now shifts to planning a safer and sustainable remission strategy. Important to note that GCA patients are older, many have comorbidities such as diabetes, failed cardiovascular disease or psychiatric risks. So long-term steroids are problematic in these patients, and that’s where steroid spearing agents come in. Tocilizumab has been used for years and in JTA weekly injections, reduced relapses and allowed for steroid spearing, but the burden of weekly subcutaneous administration, insurance approvals, injection site reactions are real in these patients.

And RINVOQ is the first oral JAK inhibitor approved for GCA. The select GCA trial randomized this patients to RINVOQ 15 milligrams daily plus a 26 week glucocorticoid taper versus placebo plus 52 week taper. And we saw as far as the results are concerned, so we saw a sustained remission of about 46% in the VO group versus 29% in the placebo placebo group. So significantly higher remissions were seen, sustained remissions were seen, and the medium cumulative steroid dose was 40% lower in patients, and they also had lower serious infections and with no higher me events in the group. So really it is an option for long-term therapy and as a steroid sparing agent. And so specifically in patients who we anticipate having difficulty tapering steroids or where glucocorticoid toxicity is a major concern. So again, frail patients, diabetic patients, patients with osteoporosis steroid sparing agents definitely make sense as an early add-on, but it’s important to also consider the real world considerations.

So no immunomodulatory therapy or immunosuppressive therapy is without risk. For example, rainbow carries blocked warnings such as infections, thrombosis, malignancy, and mace. And that said, at least in the select GCA trial, the adverse event profile was reassuring likely because of the reduced steroid exposure in this group. But it’s important to consider access prior auths and post coverage and patient preferences. So important to keep all of those in mind. But my approach is typically that I would use steroid-sparing agents along with steroid taper in patients where I suspect that I would have difficulties tapering these patients off of steroids or where the risk of toxicity from steroids are we, for example, diabetics osteoporotic patients. So these are the patients that I would consider adding asteroid sparing agent such ASIN work. And so really in conclusion, GCA is a vascular emergency, so we should treat it like one.

This is one of the few emergencies in rheumatology, and it’s important to initiate high dose steroids immediately, especially if the vision is involved and the patient has any kind of visual symptoms, the diagnosis needs to be confirmed in parallel. So consider temporal artery ultrasounds if these are available, the inflammatory markers, temporal artery biopsy, and in select patients consider CTN PET CT and think early about steroid sparing agents such as tocilizumab or invoke, which both have a place in select patients. And as physicians, our job is really to prevent harm both from the disease and for our treatments. So recognizing GCA early, treating it aggressively and planning wisely, that’s how we can preserve site function and quality of life. Thank you very much.

Giant cell arteritis or GCA is an autoimmune disease that causes a granulomatous arteritis of the aorta and its branches with a predilection for the arteries of the head and neck. GCA is a medical emergency because untreated inflammation of the cranial and large vessels can lead to irreversible complications, most notably permanent vision loss or aortic dissection. These risks can occur rapidly, so delayed treatment can result in catastrophic life altering outcomes. As soon as giant cell arteritis is suspected. I initiate high dose glucocorticoids immediately, often before confirmatory testing because the risk of vision loss or ischemic events is too high to delay. Same day treatment protects the patient while diagnostic workup proceeds in parallel. I always start with a thorough history, a focused clinical exam and labs like the ESR and CRP, and then I tailor further testing based on the presentation. If GCA is suspected, I collaborate with our vascular surgeons to arrange for a temporal artery biopsy, ideally a three centimeter segment to account for skip lesions, which are classic in GCA, which still remains the gold standard for diagnosis.

Vascular ultrasound can be a helpful non-invasive tool when performed by experienced technicians. Not all centers have that expertise, but when available, it allows for same day evaluation and supports timely decision-making. MRI and CT are generally inadequate for ruling in or out giant cell arteritis. While some academic centers are developing specialized cranial MRI protocols, these remain experimental and not widely validated or practical. Outside of research settings, having an oral option like RINVOQ with a favorable safety profile and proven efficacy gives me confidence in personalizing care. Beyond steroids, it means we can think about remission and long-term safety from day one, not just acute control. Clinicians should think of GCA in any patient over 50 years old with new onset, severe continuous headache, sudden vision loss or diplopia limb, tongue or jaw claudication, not to be confused with TMJ dysfunction and scalp sensitivity and a substantially elevated E ESS R or CRP. The key is to act fast. Start steroids when you suspect it, refer urgently and flag it as a time sensitive diagnosis.

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This video was created in collaboration with AbbVie.