Fever of Unknown Origin

I'm Adam C. Fiew, and I'm Scott Stern. And we're here with another episode of S2D, The Symptom to Diagnosis Podcast. This podcast teaches evidence-based strategies for diagnosing common medical symptoms. We begin each episode with a case, unknown to one of us. We then discuss five high-yield features that help to accurately diagnose the cause of the symptom in hand. We then return to our case before finishing up with a discussion of fingerprints, common misconceptions, pet peeves, and other random pearls of knowledge. The cases that we discuss are drawn from our clinical experience, but because protecting patient privacy is part of our oath, we never discuss actual patients. What are we talking about today, Scott? Today, we are talking about F-U-O, otherwise known as fever of unknown origin. Interesting. Interesting. Unfortunately, you're the expert, and so I have to listen to a case of fever of unknown origin, which I imagine is going to be challenging, but I'm here for you. Aha. Well, good. This will be fun. I'm going to torture you. Okay. Are you ready? Yeah, I am. Okay. Our patient is a 92-year-old man. How do you like that? Great. Well, last five weeks, referred from an outside hospital. He says his highest temperature has only been 100.8. He had a day or two of diarrhea when it started, but that resolved and had a sense, no abdominal pain, no cough, no urinary symptoms, and that was it for his chief complaint. Okay. Would you like to know his past medical history? Yeah. I don't know much to go on. So I need something. So he had bladder cancer years ago, and he had a resection, and then he had a perioperative installation of chemotherapy and it was bladder. That was 10 years ago, and no, no, in recurrence. He had a history of previously being noted to have diverticulosis, with never having had diverticulitis or a bleed, and a history of hypertension. His social history quits smoking about 20 years ago. He drinks a glass of wine every day or so, and no recent travel. Would you like his outside labs, because I had those when I first saw him? Sure. So he's been hospitalized, and then shred, no, no, no, he's just been seeing a doctor on the outside, and he's transferred to you, and they couldn't get to the bottom of it, so he came here. Okay. So his outside labs, he's had several. So his white count has been anywhere from 22.9,000 to 17.6,000, with a little bit of a left shift. Okay. His hemoglobin is 31.5. Okay. His platelet count was 276,000, and when his height is 473,000, he actually got bone marrow biopsy, which was shown only reactive changes. I mean, he had a chest x-rated that was unremarkable, a COVID test that was unremarkable, a comprehensive metabolic panel that was normal, except for our creatinine that was 1.8 at its maximum, I think actually 2.0 at its maximum, and he'd been maybe 1.5 years before, so it wasn't a dramatic change. Your analysis was negative, and his CRP has gone from, let's see, 16 and then 19. Okay. And does he take any meds for all of his? Yeah, so he takes, you know, am low to peen and low-sarten, and he's on Symbasatin first cholesterol, because we know that works well in 92-year-olds. And I'm going to assume that that's been for a while, those guys. Nothing new, right, exactly. And then an exam, when you first saw him. So he was a February one, I saw him, you know, didn't look toxic or anything. His H&T exam was only marked while I looked at his teeth, there wasn't, you know, any clear infection, thyroid felt normal. As long as we're clear as cardiac exam, you know, regular, normal sinus rhythm, no murmurs, no gallops, I abdomen was completely soft, non-tender, no masses, prostate exam was enlarged, but so off to no duration, no nodules, and not tender. Okay. Okay. Well, that's tough. So, you know, hearing it, the first thing that I always do is say, you know, is this really, you know, a fear of ununorigin, so I think about, has this gone on for a long time. It sounds like this has gone on for a long time. And then I often, because I so try not to, you know, get too excited about things until I'm convinced. I actually try to sort of make sure that people really have an FUO and this guy, you know, you're seeing him, he's in hot febrile when you see him, he's got like a really unimpressive CRP. I think I'd approach this where I'd sort of say, look, I'm going to do a couple of things, I'm going to trust that this is actually real, I'm going to do a couple of things now. But I probably wouldn't go crazy at the beginning, because I'd like to sort of under my control see if this is real. So, you know, I'd send him home with a thermometer and tell him, you know, hey, you're taking a temperature four times a day and you're going to report that to me in a week because I see what's happening. I think with what you've told me, the couple of things that come up, you know, so this guy's had a diverticulosis in the past as probably all 93 year olds have. I expect you went real deep into his left-floor quadrant, you know, diverticulitis is something that can certainly hang out. I'd be kind of maybe a little more, well, certainly more careful than usual on his physical exam. I usually do a rectal exam in men, you know, make sure there's no prostitutitis there. I kind of whack on people's sinuses, though I recognize that that's not terribly specific. See if there's a sinusitis hiding there. I think in this guy before sending him home, you know, I would do blood cultures, I might do a c-diff since it sounded like there was some diarrhea at the beginning of all this. And then, you know, I wouldn't make a whole lot, I guess, of the white count now just because it's been there and he's had a bone marrow biopsy. I sort of don't think the marrow is going to be the answer here. I think that's going to be reactive and the platelets go along with that. So I think I'd say monitor your temperature for a week. I'm going to send off those things to begin with and let's just kind of watch you. Okay. Would you like more information now or would you rather us go into the pivotal point for this? Why don't we wait and then we'll talk a little bit more. All right. It sounds okay. So let's leave the case and why don't you give us the five key points? Five key points. So first we should start with definition. The definition of an FUO is actually pretty capricious. It's thought to be a temperature of greater than 38.3 on several occasions over two to three weeks, despite intensive investigations. Now here's the problem. FUO agrees on what the intensive investigations are. Nor does anyone agree on the two to three weeks. So FUO is ill-defined entity that basically means someone's having a fever that is somewhat prolonged, at least more than a week or two, because that gets rid of a lot of the viral syndromes that often, you know, we don't diagnose and we don't really care about. I have something to say, but I'm going to save it because it's pretty much my only pet peeve here, and I don't want to, you know, lose something early. Okay. Well, then point two is we can organize the differential diagnosis of FUO in a three large buckets, if you will, by far and away the most common is infectious. And then there's malignancies in rheumatologic diseases and the frequency of each of those varies depending on what cohorts being looked at, frankly. And my understanding, and it's kind of cool as you read about this, that not only is the definition changed over time, right, because our diagnostic tests have gotten more specific, you know, FUO lasts less long these days, because we forget to figure out faster. And also the breakdown, or let's say the size of your three buckets change, right, where actually infectious disease has shrunk in retrospect to malignancy and rheumatologic disease. That's right. And I saw the same things. Great. Point three. So, obviously, what you tried to do initially, which is you really need to look for clinical clues. The differential diagnosis is just enormous. And if you're starting blind, it's pretty tough. So you do need a really thorough history, including a comprehensive review of systems. And a really detailed physical exam that, as you mentioned, would include a rectal exam in men and a pelvic exam in women. And then you follow up on those clues. It's unlikely to give you the diagnosis, but it might tell you where to look next. So obviously a cough or just need a point to looking at the lungs in more detail with imaging. Diaria can point to a GI infection. Abdominal pain might point you to looking at the CT scan of the abdomen, urinary symptoms. So obviously, we'll point to that area headaches. Could suggest something like temporal arthritis, not an uncommon cause, or in its epilitis, meningitis. One thing we've seen a couple of times in the hospital is patients who have epidural abscess who present with not much pain, but weakness in the leg. So weakness should really get your attention if they have it. Joint pain could suggest rheumatic disease. And you do want a careful lymph node exam, because lymphomas can do this. You want to check for a splinter, mygly. So I can't emphasize enough, really, just the detail of the physical exam. I think fever of an unorigin, maybe with overlapping fever and neutropenia is about the only time in medicine where you're actually going to do your head to toe physical that you learned, and physical diagnosis, or clinical skills, or whatever it was called where you trained. Because it's the one time that you're like, I don't know, I'm just going to look for everything. And what's interesting with FUO is that if you find something, so if you listen really carefully in a quiet room and actually do a full lung exam, and you're like, huh, I actually hear some anterior rails. It's probably not a chest x-ray, which is going to be the answer, because that's probably already been done, right? So you're actually probably following up physical exam abnormalities with maybe more invasive tests than you would normally, or more detailed tests, not necessarily invasive. Sure. What do you mean? How about we settle on more expensive tests? Yes, for sure. I think the other symptom that does that is weight unintentional weight loss, because again, it's the differential is just enormous, and you need a clue. Yeah. You know, unintentional weight loss. And you find so much out in the history for unintentional weight loss, right? Although there's so many people you don't diagnose at all. I know. All right. I think we've talked about that already. I think we have actually. Maybe when I dementia, I don't remember it. Okay. So the third point is then what do you do when your history and your physical aren't pointing to something specific? And there's a baseline set of labs, I think most people would do, although I don't think there's actual, you know, confirmation of this. You would do a CBC and a comprehensive metabolic panel. These days you're going to do a COVID test, right, my HIV test. Of course, a monospots recommended, an A and A as a screen, I guess, for lupus, a serenproaching electric freezes for multiple myeloma, a PPD or a quantifier, depending on where some, whether or not someone to have BCG, just to refresh our audience. The trouble with BCG, which is a vaccine that's given in many parts of the world to prevent TB, is that in many patients across, we actually, the PPD. So patients who've had a BCG, so you actually get a quantifier on test, which doesn't cross over with the BCG instead of a PPD. So I think I got all my abbreviations correct on that long diatribe. UAA and a chest X-ray, blood cultures, like you said, and some authors also recommend an echocardiography to look for signs of endocarditis. Just to disrespect your age a little bit. I think we've, like, just given up on the PPD, right? No, he's quantifier hunt for everything now. You're just screening people for work, which you probably shouldn't be doing anyway. We just do quantifier hunt. You know, we don't do PPD. It's certainly simpler. You don't have to inject it. People don't have to come back. I don't disagree. It is. Yes, fair enough. Do you remember getting the time test from your kid? Yes, I do. Little four-low pokes. Yeah. I do remember that. My pediatrician used to draw a heart around it. Not very nice. So you could see it again. That's right. Do you remember the oral polio vaccine? I do. Do you remember that? There we go. And the small pokes vaccine. Me too. All right. Now that we've told everyone how old we are, should we carry on? Yes. Please. Okay. So the fourth key point is when everything else has been negative, it is appropriate to do a CT scan of the chest abdomen and pelvis. The reason is a lot high. Do you've already mentioned that anterior ryls might suggest you don't upper a little bit infiltrate. Those are not well seen on chest X-ray. And similarly, a lot of infections and tumors in the abdomen can really hide and not be very impressive on physical exam. You know, a lot of patients are overweight and so it's hard to feel. And also, retroperitoneal findings are not going to be palpable on physical examination. And I've seen, you know, renal cell carcinomas present with F.U.O.'s and absesies present as F.U.O.'s and fiel carcinomas present as F.U.O.'s. So it's really appropriate to go ahead and do that. One thing I read that was really interesting was some authorities have recommended getting a PET CT instead of a pan CT in this patient population. I have to say I've never done that. The idea is that tumors and infections are often fluoroxyglucose avid because of their high metabolic rate and that those tests of PET CT is more sensitive than a regular CT in this situation. Have you ever done that? I've done it as a second line sort of post CT not found anything. Did it help? It did help actually in this single case. What was it? It was actually a lung cancer. Really? Yeah. Small enough just not seen on the original CT. Well, now I should do it on everyone because you know the way I am. Yes, I do. Yeah, I just shouldn't have said anything. To highlight one thing that I just missed and it's sort of easy, but it's just interesting to sort of reflect on, you know, what COVID has changed. That I have had one person in the last two years who had, and these were not like great diagnoses because like everybody is COVID. Of course, you're going to check it. But someone who really presented just with a week of fever, nothing else, and I know we should do a COVID test. COVID test was positive. You know, no URI symptoms, no influenza-like symptoms, just a fever. And another woman who really just presented with fatigue. And it was two weeks of a horrible fatigue. There was no kind of, you know, preliminary URI symptoms, nothing. Our COVID test was positive. We sort of waited out and it got better. It was interesting. Well, you know, we do know that uncommon presentations of common diseases are common. And now we have something that's affecting millions of people, so we can almost expect for sure we're going to get weird presentations. Good point. Okay. Well, why don't you bring us home with number five? So the fifth key point we should talk about together, which is there are a variety of special populations where you're going to say, oh, this person has FUL and X. And because of X, we're going to think about other things. I'll start with Diabetics. Okay. Diabetics, one of the places infections loved to hide in patients who have diabetes is foot ulcers and osteomyelitis. So the data on this suggests that foot ulcers can lead to osteomyelitis in patients with diabetes without really much of a remarkable physical exam. It can look like a fairly benign ulcer and yet be right into the bone. So I would recommend that if you have a patient with diabetes who has an FU on a foot ulcer that you proceed to MRI, even if it's an unimpressive physical exam. I'm also going to say really exam in the foot. I've seen two people who I was brought in. They had foot pain and the report was there's nothing really there on the foot. And when I actually like really squeezed, pushot out and so like you got to get in there and you got to make sure obviously that would have been turned up on the MRI. But you know, you can get some clues. Another, this you go under clinical pearls, but I got to tell you, smell can help you in this situation because diabetic foot ulcers and anaerobic ulcers often have a really nasty smell. So shocking enough, if you walk into room and it really smells bad and you're kind of repulsed, you really want to look at the legs and the feet carefully because you might, that might be your clue that you're looking for. Yes. Do you have any special populations you think about? Maybe I'll go with the, you know, most obvious one is HIV, right? And HIV, I feel it's, it turns, and this is obviously late stage HIV, very immunosuppressed. This is often not that you have no idea where to look, but you have multiple places to look and it's just figuring out, you know, what the hell is causing the symptoms. M.A.I. is certainly a possibility. You need to culture for that. Sometimes a bone marrow biopsy for that. Dr. Kakas, CMV lymphomas in HIV can be an issue. That's often something that you're going to turn up just on imaging and that's often difficult because there can be just underlying HIV associated lymphadenopathy and it's distinguishing that from the lymphoma endemic mycosis, right? Things that don't cause symptoms in most people, but can cause symptoms and real illness in HIV. So a huge number of things that you may turn up in the work up in HIV. Yeah. That's definitely true. I see that a lot. Oh, all the time. Of course. Unfortunately. Another population I would talk about are people who've been hospitalized with various conditions. So patients have an individual in catheter and they have an FUO. You better just assume it's infected regardless of what the site looks like and pull it and culture it. A neutropenic patients are completely different kettle of fish as are any immunocompromised patients and it would be who of anybody who's taking care of patients immunocompromised with FUO is to look up what that particular drug that they're on puts them at risk for. You know, in neutropenia, for instance, we know we need to worry about staff, pseudomonas and if the fevers persist, fungal infections, but transplant recipients and many other immunocompromised patients have different sorts of infections and that should be looked up at the time. Great. And I guess, you know, you mentioned that thing about hospitalized patients. It's that patient who develops fever in the hospital that doesn't go away or so difficult. See diff is an obvious one. And then all of the medication-related fevers and it really takes some courage where you're like, you know, we've worked up everything. This person's on three antibiotics, nothing's changed. We just need to stop everything in a stable person where then you say, look, they're in the hospital. If they go bad, we're going to know immediately. But on occasion, all of a sudden, everything gets better and you never really know which of the three antibiotics was causing the fever, but the person's better and so does really matter. Right. I mean, that's really a good point. And the tough part about that is the fevers are often from antibiotics and so it takes a certain amount of a hootspot to say, fine, they're still doing food, I'm going to back off. Right. It's not the intuitive sort of, you know, knee-jerk response. When you do that, you end up just moving into the patient's room so you can observe them 24 hours a day. You're taking clonipin four or five times a day, I think. Another group to think about are elderly folks. You know, elderly patients, some of the rheumatologic conditions are particularly common such as polymout acid, redmatica, and temporal arthritis. And so a sederate in a CRP, if they're high, could lead you to think about those, maybe think about temporal artery biopsy and so on. Good. And then probably the last thing is people with travel history, whether it's, you know, recent travel just done vacation or immigrants who've spent, you know, decades in other places. This just leads you to look stuff up, you know, it's just to say, okay, you know, what are the endemic infections in those regions? What is something that someone could have picked up and brought home, or is there sort of, you know, endemic, I don't know, fungal infection, parasitic infection that that person might be showing signs of now, often late in life, you know, when the immune system is waning. Right. TB being huge. All right. So you wanted to send him home and see how he's doing. I did. But wait, wait, I asked for some stuff. All right. What did you want? I asked for blood cultures. I asked you to get a glove and do a rectal exam. I think that was about all I asked for. So I had done a rectal exam and it was negative. Okay. Good. The blood cultures were no growth and the CDIF was negative. Okay. Okay. And so had the guy do. Well, not so well. He continued and I feel well, I'd gotten, you're going to be surprised at this. I'd gotten a few more labs. Let me see if these few more labs might alter your thinking. So I thought, well, he's elderly, his temperature is low grade. Let's get some more labs. His repeat, Y count was 18,000, 80% neutrophils, the hemoglobin was still 9.6. His said rate was 18, his CRP was 186, our upper limit on normal being 5. His CMP showed his crating was maybe up a smidgen 2.3, his album was 3.2 and his LFTs were normal. So thoughts. You're in on this visitor now. Negative. Okay. Now I'm actually more concerned. The White Ken still doesn't do a whole lot for me. I do think he's chronically inflamed with this anemia in these elevated platelets. That CRP through the roof is being think, wow, there really is something here. The only thing that there's any reason to focus on, I guess, is this creatinine. And often 93 year old guy, not surprising that his creatinine's up. But it does sound to be up from his baseline. It seems to be rising. And so if there was a place that something might be hiding, maybe it's the kidneys. And so I'm left with, geez, you know, what's the next test here, right? There's nothing in the urine. And so I think maybe I'm at the point where I need to scan this person. And you know, the risks are kind of there with giving him contrast. So I almost might start with a non-contrast abdominal pelvic CT. And I would tell the guy that like, look, this might very well be negative. And we might have to take a larger risk with a contrast exam like a week later. But in someone in their 90s, you're not really that worried about radiation exposure, right? You're not going to have consequences of this in 20 years. So what happened next? So I did, there are calculators, as you know, for AKI, I looked over the calculations. The risk of contrast nephropathy was somewhere between 10 and 20%. But the risk of contrast nephropathy to the point of cause of dialysis was only in the very small percentage ranges. So I held my breath and did a CT with contrast. Although I think your proposal would have been reasonable. And that showed massive diverticulitis. Despite his unremarkable physical exam, he had a flagman that you and I could read, abdominal CT that went from the pelvis up to the spleen. And from there, it went poorly. I'll remind you that I did comment on that. Yes. And I suggested that maybe you do a good abdominal exam, which I did not do at an exam exam. And elderly patients are tricky. Yeah. That's interesting. Was he heavy? Was he a different one? Well, I mean, he was, you know, by our standards today, I wouldn't say, you know, probably 220 pounds. Yeah. Not cactic. Not cactic. Interesting. Obviously antibiotics that he needs surgery. Well, you know, we did put him on antibiotics. We were trying to avoid surgery because of his age and just cradding and whatnot. And then he became septic on antibiotic and went to surgery and didn't survive. Boy. Boy. You wonder if the diagnosis, you know, had been made earlier, right? That's a tough case. Okay. Let's move on to our famous finger prints, common misconceptions, pet beaves and other random pearls of knowledge. You want to start us off with fingerprints? I don't have any fingerprints. Yeah. And in fact, obviously there are no fingerprints, right? Because if there were fingerprints, it wouldn't be a fever of an origin because you'd make the diagnosis. I kind of like the fact, and maybe this goes a little bit from fingerprints or the fact that there isn't. When you mention this a little bit to begin with about, you know, what we think about, when we think about FUO, it needs to be persistent, right? And the fact that it needs to be persistent does a couple of things. It limits the differential diagnosis, right? Because when we think about things, everything, everything, everything that should go away quickly is off the differential diagnosis, right? And it also then assures that an evaluation is warranted because even if there's something that, wow, we've got to find that. If it's gone away, you know, who cares, we don't worry about it. It also really limits the number of patients who need to be evaluated. So, you know, we talk about this, like, oh, FUO, of course, it's something we should talk about on the podcast, but, you know, it's really, really rare. I know. I was thinking about that. I think I've probably only evaluated, it's probably every couple of years between an FUO, I think, maybe even that I've seen, maybe even every five, what would you say? I would say the same thing. I think it's more common that, like, I'm referred in FUO, and it doesn't actually turn out to be anything, because once you actually just, like, step back, pay attention, it's like, this isn't the problem, yeah, okay, common misconceptions. So, it's probably worth talking about temperature a little bit. So, what's normal? You know, the really fascinating thing is the idea that 98.6 was established, are you ready for this? 98.68, at a time when there were probably more chronic infections and inflammatory conditions going on. So, it was a survey of a zillion folks, and the average temperature is 98.6, probably a more normal temperature for the average person these days is 97.5, and it may be that it's even be lower than that in the elderly. The elderly don't mount responses as well, and I'll come back to that in a little bit. Yeah, it's so cool, and, like, the thinking is that, you know, those measurements probably included people with chronic infections, right, and also that we're just generally less inflamed, right? It's wild. And I've seen sort of, like, you know, how much our temperature is declining per decade, it's, like, wild. Well, I would have part of that as our food sources, you know, we don't have as much chronic intestinal inflammation, because we don't have as much chronic exposure to infectious agents in our gut. Yeah. Yeah. Um, common misconception, this is a little bit of a stretch, but that algorithms are helpful in the diagnosis of FUO, okay? I do this only slightly to bother you, Scott, because you've got, don't you have an algorithm like tattooed on your shoulder blade? I think I have many of them on my back. It may be a map. I should just do a map of all the algorithms on my back. There are good algorithms, and, but I would sort of point out maybe the most recent reference, which a lot of people have read, is there was a terrific, terrific review of fever of unknown origin, actually, in the February, 2022 New England Journal. And there are algorithms there, but the algorithms are so sort of generic, because it's basically think about the patient, work up the individual patient you have, and then if you get nowhere, do really broad imaging, right? And so FUO in a way is not something that we do algorithmic care for. Right. That happens. Do the careful history and physical and look for clues, right? Yeah. Pet peeves? Shall I start? Why don't you start? So my pet peeve is absolutely not being alarmed by low grade fevers in the elderly. It turns out that elderly patients have trouble mounting high temperatures, and there was one study that documented that 20 to 30% of elderly patients who had serious infections actually had either no fever or a very wanted response. And another study found that in patients over 80, who had a fever of 101, virtually all of them had a serious infection. So unlike children and young adults who mount fevers easily, the elderly really don't. And you need to be alarmed when they come, you know, you get an elderly patient's 102 point. You almost should put them in the hospital, because you know what's causing it. Yeah. Yeah. That's true. It's a bit of a stretch. I'm remarkably about this chill about fever and non-origins. And I think it's because what usually drives me crazy is excessive evaluations. And FUO, you know, if there's been a fever and it's been around for a while, you know, it's causing it. It kind of deserves an excessive evaluation. So I'm okay with this. But I did work to kind of manufacture a peeve just for the good of the podcast. And something that does bug me is really the name, right? We never discuss, ooh, it's a headache of unknown origin or chest pain of unknown origin. So really, this should just be called prolonged fever, right? And there is a list of diseases that cause prolonged fever. And there are evaluations for those cause of prolonged fever. And if you said, you say, huh, I've got someone with a prolonged fever. You know, this is a differential of prolonged fever. I got to figure out how I'm going to go after it in this individual patient. So when we rule the world, what we should is change the name of a couple of diseases. I'll let you change this one. If you let me change community acquired pneumonia, okay, because that captures all the different infections and people stop thinking it makes me crazy. Right. Deal? If we could call it CFU's prolonged fever fever. Okay. All right. Let's go on to clinical boroughs. Okay. You start. All right. In this case, illustrates the old adage that uncommon presentations of common diseases is a much more frequent phenomenon than rare diseases or typical presentations of uncommon diseases. He had a common disease and he presented a typically. Now we know elderly and children often don't present typically, but it's just true and it's just interesting. Right. And then I guess my pearl is, um, think about FUO and travelers, right? I sort of mentioned this before in a way, you should be excited if you have someone who's recently traveled who has a fever and you don't know what it's from because, you know, it may not be something exotic, but at least it's going to take some work. Our infectious disease doctors are, you know, spectacular, um, with this, the things that lead the list are certain, certainly malaria and taric fever that we don't see a whole lot, leptosporosis and a really, really, really rare cause, um, which I always comment on is airport malaria that I think there's been like 70 some cases, you know, in the literature so it's really rare, but it's people who have not been someplace interesting where they may have gotten malaria, but they've gone through airports that have travelers from interesting places. And I don't know. So mosquito got on the airplane and, and bit them and they end up with malaria. It's about the worst luck in the world, but it's pretty interesting as a doctor. That must be the most nerdy comment in the entire podcast that I think that wins. All right. You know, we're a clinical pearl and that's it with shaking chills. So patients often say that they're chilled and what you have to distinguish is whether they just felt chilly and cold or whether they were physically shaking. It turns out that there is a strong correlation between physically shaking chills and bacteria. Now, there's no doubt influenza can do it and some of the viruses can do it, but you should absolutely ask patients when they feel chilled, where they physically shaking. If I was in the room with you, would I have seen you shaking or you're chattering? If so, be worried. Yeah. Good. I got one more I'll throw in just because as two internists, we should say this, FUO blame the surgeon. And what I mean is if you have a patient, you know, with a prolonged fever who recently had surgery, just think, ah, it's got to be the wound, right? People are far enough out that they're not having fevers from antelecticists. They're not having, you know, urinary tract infections. They're not having urine symptoms, you know, and it may be something very mild. It might be, you know, a small collection in the incision, but that's clearly the place to go first, if you're looking for something. You know, they did say in that New England Journal article that antelecticists is actually not a cause of fevers. I remember it's conception. Is that right? Yeah. Is that interesting? So that wind, wound, water, right? They mentioned that a lot of patients postoperatively have inflammatory fevers in the surgery, but if it persists, right, right on is to look at, look carefully at the wound in the area. Good. Well, we hope you found this episode of S2D, the symptom diagnosis podcast useful and a bit enjoyable. As a reminder, our textbooks, symptom diagnosis and evidence-based guide takes a much deeper dive into how to think about and reason through the diagnosis of medical presentations, though there's not a chapter on a few, oh, this time, this time, we're thinking that for addition five. Yes, we could. We could. The book is available in print through all the usual places on your mobile device and also available and fully searchable via the Access Medicine website available worldwide from McGraw Hill. The music for the S2D podcast is courtesy of Dr. Maelan Martinez. [BLANK_AUDIO]