 All right. I think we'll go ahead and get started. Our presentation today is from our star VA intern, Ashley Byrne Heisel, who's been navigating mountains of paperwork and doing a great job. So we'll let her get started. All right. Today's case is about an 80-year-old man who walked in to my clinic from the VAED. His main complaint was that he had a sudden decrease in his vision in his left eye. He described that his vision loss started two days prior to presentation, and the first day it was just blurry, and then the next day it was as if a complete current had come over his left eye, and then he didn't make it in until the next day, as most of that stories go. He denied any associated flashes of light, floaters, no headache, no eye pain. His past medical history is congestive heart failure, hypertension, sleep apnea, some dermatitis, aphib, some severe left lower extremity neuropathy in which he needs a cane for COPD and hyperlipidemia. Here's his long list of medications, again, as most of our butts have. His prior ocular history is pretty minimal. He did have both cataracts done in July of 2013, about two weeks apart. He was last seen in ophthalmology clinic in August of 2013. At that time, he was given artificial tears for myelobliferitis, and his vision at that time, about a month after cataract surgery, was 2025 in the right eye and 2030 in the left. He was discharged to optometry after that point. In October 2014, so just a few months before I saw him, he was seen by optom and had 2020 vision in both eyes. So on his eye exam, his visual acuity when I saw him, he was 2015 in the right eye with correction and no light perception in the left. His pupils had a four-plus APD in the left eye, tried to measure it with the log filters, and there were not enough of them to make any difference in his APD. His sclera were normal, corneal normal, anterior chamber was clear and quiet, and his irises were normal in both eyes. On fundoscopic exam, his vitria showed no anterior vitria cell in either eye. His optic nerve, his right eye, did show a small splinter hemorrhage inferiorly. His left eye, the optic nerve was diffusely pale. There was some mild edema and some thickening inferiorly with some bright white exudate. The cup-to-disc ratio was 0.5 in the right and 0.3 on the left. His macula showed some mild AMD in both eyes, and there was no red cherry red spot in either eye. His periphery in the right eye was normal, and in the left eye there were some attenuated vessels. Here is his fundoscopic exam photos. You can see in the right, you can still see the borders clearly of the optic disc, and there's just that minor splinter hemorrhage inferiorly that you actually had to look a few times to really even be able to notice. In the left eye, you can see that those borders of the optic nerve are more difficult to define, and although it is very pale, not quite chalky white, but there is a little bit of a cotton white spot inferiorly. Now the pictures kind of make it look like there is a cherry red spot, but I think it's just the way that these are developed. So the differential at this point, the biggest on my differential at first was NAION, also AEON, and really there's a large differential. It could be an infiltrate, toxic metabolic demyelinating. So walking in the diagnosis in this patient, I'd ask a few more questions. So he continued to deny any kind of headaches, no jaw claudication, no girdle weakness. He did feel like he had some loss of weight. When I initially asked him, he said, oh, yeah, I've lost some weight. It's been really slow over the last couple of years. I think it's just because I'm getting old. When asked again later, he said, oh, yeah, I guess my appetite's been pretty poor lately. So comparing his VA picture that's in the system compared to how he looked at that moment, there was quite a bit of thinning temporally. So when evaluating his temporal arteries, right anterior to his ears, he actually had pulses bilaterally. But it wasn't until I felt up more in the ocular region that you actually lost the pulsation in the left temporal artery. But there was no tenderness. So based on the severity of his vision loss, the optic nerve appearance, his weight loss, and then the loss of the pulse in the left temporal artery, we decided that this was definitely GCA. So that's what we used to decide he had GCA. However, there is no really clear classification criteria. What is available is largely based off of a 1990 study published by the American College of Rheumatology. So this study, the main point of the study was to really compare GCA to other vascularities. And it was from that study that they came up with a sensitivity and specificity of 93-91% if the patients have three of five criteria. However, it's kind of been adopted as just diagnostic criteria for temporal arthritis in general, even though that was never the intended purpose of the study. So here's that table. I call it a differentiation table because it really wasn't meant to be a classification table. So if patients either have an age over 50, a new headache or a new type of headache or head pain, ESR greater than 50, temporal artery tenderness or a loss of pulsation or a biopsy specimen, then those are the sensitivity and specificities if they have three or more. So just a little bit about temporal arthritis or GCA is now more common term. It is the most common vasculitis affecting people over the age of 50. It's most common in Caucasian females. The female to male ratio is about 2.5 to 1 and visual symptoms occur in about 30% of patients and a lot of studies have a large variety as far as what that's quoted, but 30 appears to be about the average and about half of those end up being permanent vision loss. So it tends to occur in medium to large size vessels of the head and neck and prevalent studies again are buried about 100 to 300 per 100,000 patients and incidence is about 3 to 22 per 100,000 and the median age is about 70 years. So as ophthalmologists, an important question is whether or not we can predict which patients will end up with permanent vision loss. So the answer is that if their vision is still transient, if they have double vision, if they're having a curtain come over their eye and then go away, if they're kind of in that waxing and waning stages, if you start them on a corticor storied in that time period, then you're more likely to preserve the vision. However, once they have a defect, it's pretty much going to be permanent. So what causes this disease is really poorly understood. We do know that it is an autoimmune disease. Some various studies have shown that there's seasonal and geographic variation, which makes it seem more like an autoimmune disease because it looks like infections, such as mycoplasma, chlamydia pneumonia, Parvavirus-19 might bring on sort of that autoimmune inflammatory response. There are some studies that show there might be some genetic predisposition which are in HLA types and also some gene polymorphisms in IL-6 and TNF as well as other immune system polymorphisms. So some extraocular manifestations, aortic aneurysms and aortic dissections, those usually happen not acutely, but down the line. Polymyazurumatica is associated about 30 to 50% of the time with this disease, either before, with or after the diagnosis. Scalp necrosis, as you can see in the patient, is a manifestation of this disease, although it's pretty rare. You can also get stroke and MI, and the vasculitis can cover the entire aorta and even go down into the iliac arteries. So going back to our patient, he was admitted directly from my clinic to the neurology service. He was given three days of IV steroids and due to the patient's request because he only wanted to stay two nights in the hospital, he received three doses of 1,000 milligrams of IV-solu-medrol. Current recommendations are 250 milligrams IV-Q6 hours for three days. On admission, his ESR was 16, CRP 19.5, and platelets 233. So again, those aren't super high, but based on our clinical suspicion, he underwent a temporal artery biopsy, and that biopsy was positive. So talking a little bit about pathology for this disease, it's a transmural inflammation of all three layers. There can be obliteration of the lumen, which causes the ischemic complications, which I just spoke about. Infiltrates can include T-cells, macrophages, and biopsies can show skip lesions. Giant cells for which it gets its name aren't always present and are not necessary to make the diagnosis. So here's a normal temporal artery biopsy. You can see the layers here, the adventitia on the outside. Looks like things got moved around. The arrows disappeared a little. Oh, they're just really light. So the media in the middle and the intima in between. And you can kind of see the wavy lines right here that go back and forth, and that's really important to note on these because that's the internal elastic lamina, which GCA characteristically destroys. So... Yes, yeah. So the adventitia is right here, this darker layer. The contrast isn't really good. I don't know if you can see kind of where it ends, but you can kind of see right here this is kind of a thicker layer right here, and that's the media. And then the swiggly lines right here, that's the elastic lamina and then the intima is the inner layer. Is that okay? So this is from this patient, a friend who's a path resident was able to take pictures for me, which I really appreciate. So there's the characteristic of GCA, like I said before, is that there's infiltrate in all three layers, and actually I think in this picture you can kind of see the three layers even better. They all have those blue or purple spots so it's showing that there's inflammation in all three layers, and you can see that there's a blurration of the lumen here. And actually if I go back you can kind of see where the back and forth squiggly lines end because of the infiltrate. And that's kind of the line showing where there's more inflammation so you see more of the blue and the purple in that area, and that's also where that elastic lamina is not present anymore. And this is a little closer up again, and the top left corner you can see the lamina pretty clearly waving back and forth, and then as soon as you get to kind of where the purple areas infiltrate you'll lose that back and forth wavy line. So this is not my patient, he did not have any of the classic giant cells, but this is kind of what it would look like if that were the case, and then where those giant cells are or where that is where that wavy lamina should be and has been disrupted. So as I said, a lot of these biopsies can demonstrate a skip lesion, and in this case the normal that I showed you at the beginning is actually our patients. So there is different cross sections and if the cross section had been smaller and just shown this we might not have had our diagnosis. So again that's just showing the normal skip lesion. So recommendations are again variable. They suggest at least one centimeter. A lot of publications suggest over two and a half centimeters. Our biopsy was 2.9. Should be unilateral. Studies show that by doing bilateral your yield isn't that much more. And that the use of steroids should be less than 14 days starting before you get the biopsy. A lot of recommendations are that you get it while they're hospitalized. So the main kind of clinical question I wanted to ask and bring up during this Grand Rounds is should we continue to use temporal artery biopsy as our gold standard? So temporal artery biopsy isn't without any kind of cost. There can be some pain associated with it. Facial nerve injury is the thing we kind of worry about the most. When it comes to complications and then financial it is considered a surgery. We use this as a gold standard because its specificity is really high. If it's positive it's positive. And yours 100%. However, the sensitivity is not so great. It's in some studies low as 60s and 70s and some higher ones in the 90s. But there's just a lot of variability. So this question as to whether or not we should use temporal artery biopsies was first question in 1981. There was a study that reviewed 135 specimens and only about 60% of those with clinical temporal arthritis have positive biopsies. So in this old figure down in the bottom you can see the clinical diagnosis. So this is based on clinical criteria which in this case was if they had a headache, visual symptoms and a hard tender or pulsus temporal artery as well as plus or minus an ESR which is interesting because it didn't really say if they included that in all cases or just some cases. So you can see about 41% had clinical GCA and histologically only about 25%. And these were all based on these criteria beforehand they were not followed afterwards. So incongruent results and that's just pointing out that studies came out right afterwards that showed a much higher sensitivity 90 and 95% in these two studies that I have up here. And these again, so the hard thing I have looking through all of these studies based on whether or not we should use temporal artery biopsies is that they're based on the gold standard in this case is based on clinical diagnosis and a lot of them have very different characteristics and criteria for what they include in those specifications. So in 1982 publication the three things they included were anterior ischemic optic neuropathy and ESR of 91 or greater and malice. And then in 83 this one that shows 95% sensitivity was based on pathological radiological and clinical evidence. So basically anything that convinced them of GCA was included. And these ones rather than just looking at what was thought beforehand it falls them over time and if over two years they still feel like they have GCA that was what was considered positive clinical GCA. So some of these studies in the 90s were criticized because they were in areas with high Scandinavian descendants which are known to have a higher rate of GCA. And again I criticized because they use different criteria. After 1990 things get a little bit better because I talked about how that study came out and that it changed the five criteria for what is thought to be specific for GCA. So the debate continues but the question changed a little bit which I think is actually more useful. So the question becomes who cares how sensitive the artery biopsy is to change management. So starting in the 2000s there's a lot of articles based on what if you get the biopsy back does that change whether or not they're on steroids. And these three one in 2003, one in 2005 and the most recent one and actually the largest one in 2014 which had 237 patients show a range in the 70s of patients that do not change management but still that leaves 30% that are which I think is pretty significant though a lot of these papers say only 30% are changing management and maybe that's not worth it. So another study related to this looking at changes after biopsy to management. This one only 16% of the results changed management but I thought this one was a little bit more useful because they actually provide a decision tree. So they based on the ACR criteria as to whether or not you should get a biopsy. So if you only have one of those criteria they suggest that maybe you should consider a different diagnosis and not waste your efforts or the patient's time in getting a biopsy. Whereas if you have two or three of them it might be worth getting it so you can kind of differentiate and if you have four or more it's probably you probably also don't need a biopsy because you're so clinically sure. So in our so again here are those five classifications. So in our particular patient he was over 50 and he had decreased pulsation so that would be two of the criteria which would suggest that we get a biopsy and which is positive and manages GCA. So that fits nicely with our patient and a little bit more about him so in follow-up he's maintained excellent vision and his right eye ranging from 2015 to 2020. He continues to be no light perception in his left eye. He's on a steroid taper currently over the next four months. He's following up with their ophthalmology I think in another two or three weeks and then it's been seeing primary care to manage his steroid side effects. His ESR was 60 and has decreased down to two and platelets decreased. They weren't really ever elevated but they have come down and his CRP is also decreasing. I put just a star by there because HSCRP is what we have at the VA and it actually hasn't been studied at all in temporal arthritis. All it can really give us is whether there's inflammation or not but it doesn't really have a lot of relevance especially when we have ESR which has been clinically studied. So where we are now despite 34 years of studies there's not really any clear evidence as to whether or not we should use temporal artery biopsies. There's no cochlear reviews and that's partly because again all those clinical criteria for GCA are different for the different studies and therefore there might not be enough to do a cochlear review. But I wanted to put it out there and see what you guys thought. Do you think we would have changed anything and if this was your patient not just sending it to neurophthalmology but if this was your patient and your biopsy had been negative would have you changed anything based on our clinical findings and do you think that the fact that we had a positive biopsy made us continue on steroids when we otherwise might not have any thoughts on that anyone? Yeah and that's definitely one of the reasons why this is kind of a controversial topic because not only do you not want to miss the diagnosis because the consequences are high but if you don't have the diagnosis you don't really have GCA you don't want to be on steroids for two years and these are older patients and you don't want to be on steroids. But yeah like you said potentiate the side effects from those. Yeah I mean it was interesting that the papers said that 70% of people didn't have change of management and that shouldn't really justify getting one on everyone but I think that's quite a large amount. Yeah that's true. Thank you. Yeah I didn't specifically search it when I was just doing some general searches but that would be really interesting to find out. Dr. Stagg? Yeah I did I didn't like looking to him a whole lot just but that's a new thing that's coming up is ultrasound diagnosis and I think that might be something that might be added to those. What I'd like to see is some sort of again a larger kind of diagnostic tree and maybe having that be part of it so that you know if we can make a positive or a negative diagnosis based on that maybe prevent a few people from having to get the temporal biopsy. Yeah I saw a few of those too. So another study came out actually just in January of this year but it was just I didn't think it was that strong of information so I didn't put it up but there have been a few studies done in African American populations and in Asian populations and it is there but it's just a lot more rare and they aren't really necessarily done in country they're done on descendants here in the states so there's just not a lot of information available. Does that answer your question? I mean I think yes I think most people would be less likely to follow that up but I don't think it rules them out. I don't know of hand, do you know Dr. Warner? Potentially. I don't know that either. So definitely referral to rheumatology and then they could also if any symptoms come up they could potentially refer them to us after that. Any other questions or thoughts? Comments? I didn't find anything new just you know they've tried aspirin and a bunch of other things and basically non-significant findings I don't know if you know of anything else Dr. Warner? There's always something coming out. All right. Well a special thank you to my friend Justin Karoon he's a PGY2 path resident he's the one that printed out those photos for me. Dr. Warner for helping me with this case my sister she helped with those funnest photos those weren't actually my patients she helped create them with me based on other photos the patient had and then Dr. Harry who initially saw this patient with me. Thank you.