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S2D: The Symptom to Diagnosis Podcast - Episode 34: Fever of Unknown Origin
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S2D: The Symptom to Diagnosis Podcast - Episode 34: Fever of Unknown Origin
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2023-06-03T00:00:00.0000000
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[upbeat intro music] [upbeat intro music] [upbeat intro music] [Dr. Cifu] I'm Adam Cifu. [Dr. Stern] And I'm Scott Stern. [Dr. Cifu] 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 at 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? [Dr. Stern] Today, we are talking about FUO, otherwise known as fever of unknown origin. [Dr. Cifu] Interesting, interesting. Unfortunately, you are 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. [Dr. Stern] Uh-huh! Well good, this will be fun.
I'm going to torture you. - [Dr. Cifu] Okay. - [Dr. Stern] Are you ready? [Dr. Cifu] Yeah I am. [Dr. Stern] Okay, our patient is a 92-year-old man. - How do you like that? - [Dr. Cifu chuckles] Great. [Dr. Stern] Who presented with the chief complaint of fevers for the last five weeks referred from an outside hospital. He says his highest temperature's only been 100.8, he had a day or two of diarrhea when it started but that resolved and hadn't had any since, no abdominal pain, no cough, no urinary symptoms and that was it for his chief complaint.
[Dr. Cifu] Okay. [Dr. Stern] Would you like to know his past medical history? [Dr. Cifu] Yeah, I don't have much to go on so I need something. [Dr. Stern] All right, so he had bladder cancer years ago and he had a resection and then he had a perioperative instillation of chemotherapy into his bladder, that was 10 years ago and no known 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, he quit 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? [Dr. Cifu] Sure, so he's been hospitalized and then- - [Dr. Stern] No. - [Dr. Cifu] No, no, no.
He's just been seeing a doctor on the outside and was - transferred to- - [Dr. Stern] Right. And they couldn't get to the bottom of it, so he came here. [Dr. Cifu] Okay. [Dr. Stern] So his outside labs, he's had several. So his white count has been anywhere from 22,900 to 17,600. [Dr. Cifu] Okay. [Dr. Stern] -with a little bit of a left shift.
His hemoglobin is 31.5. His platelet count was 276,000, went as high as 473,000. Actually got bone marrow biopsy- [Dr. Cifu] Good. [Dr. Stern] -which showed only reactive changes. He had a chest X-ray that was unremarkable, a COVID test that was unremarkable, a comprehensive metabolic panel that was normal, except for creatinine that was 1.8 at its maximum, I think actually 2.0 at its maximum and it'd been maybe 1.5 years before, so it wasn't a dramatic change.
Urinalysis was negative and his CRP has gone from let's see, 16 and then 19. [Dr. Cifu] Okay. And does he take any meds for all of his-? [Dr. Stern] Yeah. So he takes amlodipine and losartan and he's on simvastatin for his cholesterol because we know that works well on a 92-year-old. [Dr. Cifu chuckles] And I'm going to assume that that's been for a while, those guys.
[Dr. Stern] Nothing new, right, exactly. [Dr. Cifu] And then an exam when you first saw him? [Dr. Stern] So he was afebrile when I saw him. [Dr. Cifu] Okay. [Dr. Stern] Didn't look toxic or anything. His HNT exam was on remarkable. I looked at his teeth, there wasn't any clear infection, his thyroid felt normal. His lungs were clear, his cardiac exam, regular, normal sinus rhythm, no murmurs, no gallops.
Abdomen was completely soft, non-tender, no masses. Prostate exam was enlarged, but soft. No induration, no nodules, and not tender. [Dr. Cifu] Okay. Okay. Well, that's tough. So, hearing it, the first thing that I always do is say, is this really a fever of unknown origin? 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 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're seeing him, he's not 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 I'd send him home with a thermometer and tell him, "Hey, you're taking your temperature four times a day and you're going to report that to me in a week. So I see what's happening." I think with what you've told me, a couple of things that come up, so this guy has had diverticulosis in the past as probably all 93-year-olds have, I expect you went real deep into his left lower quadrant, 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, make sure there's no prostatitis 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, 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, 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. [Dr. Stern] Okay. Would you like more information now or would you rather us go into the pivotal points for this? [Dr. Cifu] Why don't we wait and then we'll talk a little bit more? - [Dr. Stern] All right. - [Dr. Cifu] Sound okay? [Dr. Stern] Sounds okay.
[Dr. Cifu] So let's leave the case and why don't you give us the five key points? [Dr. Stern] 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.
Nobody agrees on what the intensive investigations are, nor does anyone agree on the two to three weeks. So FUO is an 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 we don't diagnose and we don't really care about. [Dr. Cifu] 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 lose something early.
[Dr. Stern] Okay. Well then point two is, we can organize the differential diagnosis of FUO into three large buckets, if you will. By far and away, the most common is infectious and then there's malignancies and rheumatologic diseases and the frequency of each of those varies depending on what cohorts are being looked at, frankly. [Dr. Cifu] And my understanding and it's kind of cool as you read about this, that not only has the definition changed over time, right?
Because our diagnostic tests have gotten more specific, Because our diagnostic tests have gotten more specific, FUO lasts less long these days because we figure out faster FUO lasts less long these days because we figure out faster 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. in retrospect to malignancy and rheumatologic disease.
[Dr. Stern] That's right and I saw the same things. [Dr. Cifu] Great, point three? [Dr. Stern] 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 might tell you where to look next. So obviously, a cough is just going to point to looking at the lungs in more detail with imaging, diarrhea can point to a GI infection, abdominal pain might point you to looking at the CT scan of the abdomen. Urinary symptoms obviously would point to that area. Headaches could suggest something like temporal arthritis, not an uncommon cause or an encephalitis, meningitis.
One thing we've seen a couple times in the hospital is patients who have epidural abscess who present with not much pain, but weakness in the legs. 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 splenomegaly.
So I can't emphasize enough really just the detail of the physical exam. [Dr. Cifu] I think fever of unknown origin, maybe with overlapping of 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 in physical diagnosis or clinical skills or whatever it was called, where you trained, right? 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 rales," 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.
[Dr. Stern] Right. For more detailed tests, not necessarily invasive- - [Dr. Cifu] Sure - [Dr. Stern] -is what you mean. [Dr. Cifu] How about we settle on more expensive tests? - [Dr. Stern] Yeah, for sure. - [Dr. Cifu chuckles] [Dr. Stern] I think the other symptom that does that is unintentional weight loss because again, the differential is just enormous and you need a clue. [Dr. Cifu] Yeah, unintentional weight loss, you find so much out in the history for unintentional weight loss, right?
[Dr. Stern] Although there's so many people you don't diagnose at all. - [Dr. Cifu] I know. - [Dr. Stern] All right. [Dr. Cifu] I think we've talked about that already. [Dr. Stern chuckles] I think we have actually. Maybe with my 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 confirmation of this. You would do a CBC and a comprehensive metabolic panel, these days you're going to do a COVID test, an HIV test, of course, a Monospot's recommended, an ANA as a screen, I guess, for lupus, a serum protein electrophoresis for multiple myeloma, a PPD or a QuantiFERON depending on whether or not someone's had 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 it cross-reacts with the PPD. So patients who've had a BCG should actually get a QuantiFERON 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.
UA and a chest X-ray, blood cultures, like you said, and some authors also recommend an echocardiography to look for signs of endocarditis. [Dr. Cifu] Good. Just to disrespect your age a little bit, I think we've like, just given up on the PPD, right? We use QuantiFERON for everything now. Here you're screening people for work, which you probably shouldn't be doing anyway, we just do QuantiFERON, we don't do PPD anymore.
[Dr. Stern] It's certainly simpler. You don't have to inject it, people who don't have to come back, I don't disagree. It is yes, fair enough. [Dr. Cifu] Do you remember getting the time test - when you were kid? - [Dr. Stern] Yes, I do, four little pokes in that little white thing. I do remember that. [Dr. Cifu] My pediatrician used to draw a heart around it.
[Dr. Stern] Oh, very nice. So you could see it again later. [Dr. Cifu] Yes, that's right. [Dr. Stern] Do you remember the oral polio vaccine? [Dr. Cifu] I do remember that. [Dr. Stern] There we go. [Dr. Cifu] And the smallpox vaccine. [Dr. Stern] Me too. All right, now that we've told everyone how old we are, should we carry on?
[Dr. Cifu] Yes, please. [Dr. Stern] Okay, so the fourth key point is when everything else has been negative, it is appropriate to do a CT scan of the chest, the abdomen and pelvis. The reason is, a lot hide. You've already mentioned that anterior rales might suggest an upper lobe infiltrate, those are not well seen on chest X-ray.
Similarly, a lot of infections and tumors in the abdomen can really hide and not be very impressive on physical exam. 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 renal cell carcinomas present with FUOs and abscesses present as FUOs and pheochromocytomas present as FUOs, 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 fluorodeoxyglucose avid because of their high metabolic rate, and that those tests, the PET CT is more sensitive than a regular CT in this situation.
Have you ever done that? [Dr. Cifu] I've done it as a second line sort of post-CT, not found anything. - [Dr. Stern] And did it help? - [Dr. Cifu] It did help, actually in this single case. [Dr. Stern] What was it? [Dr. Cifu] It was actually a lung cancer. - [Dr. Stern] Really? - [Dr. Cifu] Yeah, small enough, just not seen on the original CT.
[Dr. Stern] Well, now I should do it on everyone because you know the way I am. [Dr. Cifu] Yes, I do. I just shouldn't have said anything. [Dr. Stern chuckles] [Dr. Cifu] To highlight one thing that I just missed and it's sort of easy, but it's just interesting to sort of reflect on, 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 has COVID and of course, you're going to check it, but someone who really presented just with a week of fever, nothing else, and, oh, we should do a COVID test.
COVID test was positive, no URI symptoms, no influenza-like symptoms, just a fever. And then another woman who really just presented with fatigue, and it was two weeks of a horrible fatigue. There was no kind of preliminary URI symptoms, nothing. There was no kind of preliminary URI symptoms, nothing. Her COVID test was positive. We sort of waited out and it got better, it was interesting. [Dr. Stern] Well, 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.
[Dr. Cifu] Good point. Okay. Well, why don't you bring us home with number five? [Dr. Stern] 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 FUO and X, and because of X, we're going to think about other things. So I'll start with diabetics. Diabetics, one of the places infections love 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 FUO and a foot ulcer, that you proceed to MRI, even if it's a non-impressive physical exam.
[Dr. Cifu] I'm also going to say really examine 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, pus shot out and so like, you got to get in there and you got to make sure. Obviously, that would've been turned up on the MRI, but you can get some clues.
[Dr. Stern] This should go into 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 shockingly enough, if you walk in a 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 that might be your clue that you're looking for.
[Dr. Cifu] Yes. [Dr. Stern] Do you have any special populations you think about? [Dr. Cifu] Maybe I'll go with the most obvious one is HIV, right? And HIV, I feel 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 at and it's just figuring out, what the hell is causing the symptoms.
MAI is certainly a possibility, you need to culture for that. Sometimes a bone marrow biopsy for that, cryptococcus, CMV, Sometimes a bone marrow biopsy for that, cryptococcus, 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 mycoses, 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 workup in HIV. [Dr. Stern] Yeah. That's definitely true. We used to see that a lot. [Dr. Cifu] All the time. [Dr. Stern] Fortunately less so now. Another population I would talk about are people who've been hospitalized with various conditions.
So if patients have an indwelling 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. Neutropenic patients are a completely different kettle of fish as are any immunocompromised patients and it would behoove anybody who's taking care of a patient who's immunocompromised with FUOs to look up what that particular drugs that they're on put them at risk for.
In neutropenia, for instance, we know we need to worry about staph, 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. [Dr. Cifu] Great. You mentioned that thing about hospitalized patients, it's that patient who develops fever in the hospital that doesn't go away, are so difficult.
C. diff is an obvious one and then all of the medication-related fevers. And it really takes some courage where you're like, 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 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 it doesn't really matter.
[Dr. Stern] Right. That's really a good point. And the tough part about that is the fevers aren't often from antibiotics and so it takes a certain amount of chutzpah to say, fine, they still have fever, I'm going to back off. It's not the intuitive sort of knee jerk response. [Dr. Cifu] When you do that, you end up just moving into the patient's room so you can observe them 24 hours a day, don't you?
[Dr. Stern] And taking Klonopin 4-5 times a day, I think. Another group to think about are elderly folks, elderly patients, some of the rheumatologic conditions are particularly common, such as polymyalgia rheumatica and temporal arthritis, and so a sed rate and a CRP if they're high could lead you to think about those, maybe think about temporal artery biopsy and so on. [Dr. Cifu] Good. And then probably the last thing is people with travel history, whether it's recent travel, just on vacation or immigrants, who've spent decades in other places, this just leads you to look stuff up.
It's just to say, okay, what are the endemic infections in those regions? What is something that someone could have picked up and brought home? Or is there a sort of endemic, fungal infection, parasitic infection that that person might be showing signs of now often late in life, when the immune system is waning? [Dr. Stern] Right, TB being huge. All right.
So you wanted to send him home and see how he is doing. So you wanted to send him home and see how he is doing. [Dr. Cifu chuckles] I did, but wait, I asked for some stuff. [Dr. Stern] All right, what did you ask? [Dr. Cifu] I asked for blood cultures, I asked for C. diff, I asked you to get a glove and do a rectal exam. I think that was about all I asked for. [Dr. Stern] So I had done a rectal exam and it was negative. [Dr. Cifu] Okay, good.
[Dr. Stern] The blood cultures were no growth and the C. diff was negative. [Dr. Cifu] Okay, okay. And so how'd the guy do? [Dr. Stern] Well, not so well. He continued to not feel well. 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 white count was 18,000, 80% neutrophils. The hemoglobin was still 9.6. His sed rate was 18, his CRP was 186, our upper limit of normal being 5. His CMP showed his creatinine was maybe up a smidgen 2.3, his albumin was 3.2 and his LFTs were normal. So, thoughts?
[Dr. Cifu] Urine on this visit or no? [Dr. Stern] Negative. [Dr. Cifu] Okay. So now I'm actually more concerned. The white count still doesn't do a whole lot for me. I do think he's chronically inflamed, with this anemia and these elevated platelets. That CRP through the roof has made me think, wow, there really is something here. And the only thing that there's any reason to focus on, I guess, is this creatinine, and often, you know, 93-year old guy, not surprising that his creatinine is 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, ah, 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 the risks are kind of there with giving him contrast, And 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 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 nineties, 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?
[Dr. Stern] So I did- There are calculators, as you know, for AKI and I looked over the calculations and the risk of contrast nephropathy was somewhere between 10 and 20%, but the risk of contrast nephropathy to the point of causing 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've been reasonable and that showed massive diverticulitis.
[Dr. Cifu] Huh! [Dr. Stern] Despite his unremarkable physical exam, he had a phlegmon that you and I could read on abdominal CT that went from the pelvis up to the spleen, and from there it went poorly. [Dr. Cifu] I'll remind you that I did comment on that- [Dr. Stern] Yes. [Dr. Cifu] -and I suggested that maybe you do a good abdominal exam which you seem to have not done.
[Dr. Stern] I did a good abdominal exam and elderly patients are tricky. [Dr. Cifu] Yeah. That's interesting, was he heavy? Was he a different- [Dr. Stern] Well, I mean, he was- By our standards today, I wouldn't say, probably 200-220 pounds. [Dr. Cifu chuckles] Yeah. Not cachectic. [Dr. Stern] Not cachectic.
[Dr. Cifu] Interesting. So obviously antibiotics, did he need surgery? [Dr. Stern] Well, we did put him on antibiotics. We were trying to avoid surgery because of his age and he his creatinine and whatnot. And then he became septic on antibiotics and went to surgery and didn't survive. [Dr. Cifu] Boy, you wonder if that diagnosis had been made earlier, right?
Oh, it's a tough case. Okay. Let's move on to our famous- Okay. Let's move on to our famous- [Dr. Stern] Right, fingerprints. [Dr. Cifu chuckles] -common misconceptions, pet peeves, and other random pearls of knowledge. You want to start us off with fingerprints? [Dr. Stern] I don't have any fingerprints. [Dr. Cifu] Yeah, and in fact, obviously there are no fingerprints, right? Because if there were fingerprints, it wouldn't be a fever of unknown 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, and you mentioned this a little bit to begin with about 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, well yeah, wow, we got to find that, if it's gone away, who cares? We don't worry about it anymore.
It also really limits the number of patients who need to be evaluated. So, we talk about this like, oh, FUO, of course, it's something we should talk about on the podcast, but it's really, really rare. [Dr. Stern] I know, I was thinking about that. I think I've probably only evaluated- It's probably every couple years between an FUO that I've seen, maybe even every five, what would you say?
[Dr. Cifu] I would say the same thing. I think it's more common that like, I'm referred an 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. [Dr. Stern] Right, right. [Dr. Cifu] Okay, common misconceptions. [Dr. Stern] So it's probably worth talking about temperature a little bit. So what's normal?
The really fascinating thing is the idea that 98.6 was established, are you ready for this? 1868, 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 should 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. [Dr. Cifu] Yeah. It's so cool. And like the thinking is that those measurements probably included people with chronic infections, right? And also that we are just generally less inflamed, right? It's wild. And I've seen sort of like, how much our temperature is declining per decade.
It's wild. [Dr. Stern] I wonder if part of that is our food sources. We don't have as much chronic intestinal inflammation because we don't have as much chronic exposure to infectious agents in our gut. [Dr. Cifu] Yeah, yeah. My common misconception, this is a little bit of a stretch, but the 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?
[Dr. Stern] 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. [Dr. Cifu] There are good algorithms but I would sort of point out maybe the most recent reference which a lot people have read, there was a terrific, terrific review of fever of unknown origin actually in the February, 2022 New England Journal.
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 algorithm of care for. [Dr. Stern] Right, hence, do the careful history and physical and look for clues, right?
[Dr. Cifu] Yeah. [Dr. Stern chuckles] Pet peeves. Should I start? [Dr. Cifu] Why don't you start? [Dr. Stern] 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 20-30% of elderly patients who had serious infections actually had either no fever or a very blunted response.
And another study found that in patients over 80, who had a fever over 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 get an elderly patient, it's 102, boy, you almost should put him in the hospital unless you know what's causing it.
[Dr. Cifu] Yeah, yeah. It's true. My pet peeve is a bit of a stretch. I'm remarkably- How about this? Chill about fever of unknown origins. And I think it's because what usually drives me crazy is excessive evaluations and FUO if there's been a fever is excessive evaluations and FUO if there's been a fever and it's been around for a while, and you don't know what'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 a 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 causes of prolonged fever.
And if you said, you say, "I've got someone with a prolonged fever." This is a differential of prolonged fever, I got to figure out how I'm going to go after it in this individual patient. [Dr. Stern] So when we rule the world, what we should do is change the name of a couple diseases. I'll let you change this one, if you let me change community-acquired pneumonia because that captures all the different infections and people stop thinking, it makes me crazy.
- [Dr. Cifu] Right. - [Dr. Stern] Deal? [Dr. Cifu] If we could call it Cifu's prolonged fever. [both chuckle] [Dr. Stern] Let's go on to clinical pearls. [Dr. Cifu] Okay. You start. [Dr. Stern] All right. I just want to say that 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 atypically. Now we know elderly and children often don't present typically, but it's just true and it's just interesting. [Dr. Cifu] Great. And then I guess my pearl is, think about FUO in 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 it may not be something exotic, but at least it's going to take some work.
Our infectious disease doctors are spectacular with this. The things that lead the list are certainly malaria, enteric fever that we don't see a whole lot, leptospirosis and a really, really, really rare cause which I always comment on is airport malaria, that I think there's been like 70 some cases, 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, some mosquito got on the airplane 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. [Dr. Stern] That must be the most nerdy comment in the entire podcast, I think, that wins. All right, I have a clinical pearl and that has to do 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're physically shaking.
It turns out that there is a strong correlation between physically shaking chills and bacteremia. 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're physically shaking, "If I was in the room with you, would I have seen you shaking or were your teeth chattering?" And if so, be worried.
[Dr. Cifu] Yeah. Good. I got one more I'll throw in just because as two internists, we should say this, FUO - blame the surgeon. [both chuckle] [Dr. Cifu] And what I mean is if you have a patient with a prolonged fever who recently had surgery, just think, it's got to be the wound, right? People are far enough out that they're not having fevers from atelectasis, they're not having urinary tract infection, they are not having urinary symptoms, and it may be something very mild.
It might be a small collection in the incision, but that's clearly the place to go first if you're looking for something. [Dr. Stern] They did say in that New England Journal article that atelectasis is actually not a cause of fever. It's a common misconception. [Dr. Cifu] Is that right? [Dr. Stern] Yeah. Isn't that interesting? [Dr. Cifu] So that wind, wound, water- [Dr. Stern] Right. They mentioned that a lot of patients postoperatively have inflammatory fevers from the surgery, but if it persists, right on is to look carefully at the wound and the area.
[Dr. Cifu] Sure. Good. Well, we hope you found this episode of S2D, the Symptom Diagnosis podcast useful and a bit enjoyable. As a reminder, our textbook Symptom to Diagnosis An Evidence-Based Guide takes a much deeper dive into how to think about and reason through the diagnosis of medical presentations, though there is not a chapter on FUO. - [Dr. Stern] This time. - [Dr. Cifu] This time.
Were you thinking of that for edition 5? [Dr. Stern] I guess we could. [Dr. Cifu] 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 AccessMedicine website available worldwide from McGraw Hill. The music for the S2D podcast is courtesy of Dr. Maylyn Martinez.
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