Fever in Adults

00:01 So, we’re going to be discussing fever in adults now.

00:04 And usually, when you think about fever, particularly among adults or kids, it’s usually do to a virus, something benign.

00:11 We’re going to dig a little bit deeper into causes of fever among adults, including some non-infectious causes.

00:18 So, I’m going to start with a case.

00:20 I’ve got a 40-year-old man who complains of fever for the past four weeks.

00:24 That’s a long time.

00:25 He recently returned from a trip and is worried about his infectious disease, as am I.

00:30 So, it turns out he returned from Central Africa and he measured his temperature once.

00:35 It was 38°.

00:37 His only other symptom is fatigue and myalgia.

00:40 He has a history of gout.

00:41 He takes allopurinol and naproxen.

00:44 He’s tried a course of amoxicillin that he left over from a previous sinus infection because nobody ever throws away their drugs ever.

00:51 He found that three days of treatment didn't improve his symptoms at all.

00:56 So, what do you think is the best course for him now? What should we do for his management? Should we just reassure him and offer him antipyretics? Should we order a limited number of studies, CBC, urinalysis, chest x-ray? Should we order a more comprehensive list of laboratory work with CBC, UA with culture, thick and thin blood films, blood culture and a CMP? Or should we send him right to the emergency department for an infectious disease consult? To me, and this goes against, again, the concept of, well, family medicine usually does more let's wait and see and be very conservative.

01:33 Not in this guy.

01:34 I’d be surprised if he doesn’t have malaria.

01:37 Therefore, he needs a pretty broad workup and he may not have malaria.

01:40 He may have some other tropical diseases.

01:43 Therefore, the blood culture and the broader workup are necessary as well.

01:48 So – and we’ll talk about workup for fever of unknown origin shortly.

01:54 So, previously, the definition of fever of unknown origin required this long history of fever before it can be called FUO, and that included an inpatient workup.

02:07 Now, I think it’s a more modern definition, which is more patient friendly.

02:11 Fever measured at multiple times and there's been adequate workup either in the outpatient or the inpatient setting.

02:18 So, therefore, that broadens the number of patients who might be defined as having FUO.

02:25 What’s the differential? So, it comes down to infection in 20 to 40% of cases.

02:31 As I mentioned, it's usually something straightforward such as a viral upper respiratory infection just because those are so common, but when – in cases where it's really hard to find the cause, the source of infection, here are some tips to think about that are hidden types of infection that can fester and produce fever intermittently over time in the mouth or in the gut.

02:54 Abscesses can hide and be walled off, but occasionally produce inflammation and hence fever.

03:01 Classic for endocarditis as well.

03:03 Another place that bacteria can hide.

03:06 And then tube viruses bear noting that produce symptoms – an infection fairly frequently, either cytomegalovirus or Epstein-Barr virus.

03:14 Both of these are pretty common and both can cause symptoms over a period of weeks, including fever.

03:21 And so, you may want to think about specific testing for those viruses, and that's part of the workup I’ll get to.

03:28 Malignancy, 20 to 30% of cases of fever of unknown origin are due to malignancy.

03:34 Inflammatory diseases promote up to 30% of these cases as well.

03:39 And it’s a pretty broad list of most of the major inflammatory diseases – rheumatoid arthritis, systemic lupus, sarcoidosis, Crohn’s disease, polymyalgia rheumatica and temporal arteritis.

03:54 All of these can promote fever.

03:56 So, you’re going to look at joints, you’re going to look at pulmonary symptoms, gut symptoms and headaches and fatigue, things like that.

04:05 So, there's lots of ground to cover.

04:07 But, usually, each of these disorders, beyond the fever, comes with associated characteristics that can help you identify it more readily.

04:18 There are other causes including medications which we’re going to go over.

04:22 And up to 50% of cases, there is no actual cause found for the fever after workup.

04:32 Factitious fever is rare, but patients will sometimes use it as a way to get attention.

04:38 Munchausen syndrome, for example.

04:40 Thyroiditis can promote a fever as well, as can thrombosis.

04:47 And then as I mentioned, medications may account for up to 3% of cases of intermittent and prolonged fevers.

04:54 There it is.

04:54 Those are unknown.

04:55 I got it.

04:56 All right.

04:57 So, what kind of medications promote fever? Phenytoin, carbamazepine can do it.

05:03 H2 receptor antagonists such as ranitidine and cimetidine also can be implicated.

05:09 Even antibiotics, sulfonamides with penicillins.

05:13 And cardiovascular drugs like hydrochlorothiazide which I use a lot.

05:17 And NSAIDs too, which we use to treat fever are very rarely associated with fever.

05:22 So, is it common to see fever with any of these drugs? Absolutely not.

05:27 Should you avoid them because of the risk for fever? Absolutely not.

05:31 They are generally good drugs.

05:33 But it is something to consider in looking down the list of the differential and you can't figure out why this patient has recurrent fever after an appropriate workup.

05:42 These drugs should be considered.

05:45 In terms of the workup, initial laboratory work includes what you see there.

05:50 CBC, checking on organs with a CMP, a chest x-ray, a urinalysis with culture, and then a measure of inflammation, either a sedimentation rate or C-reactive protein level.

06:02 If that's all negative, a more thorough investigation is necessary.

06:06 Start looking at markers of tumor breakdown and cell breakdown, like lactate dehydrogenase and creatinine kinase, and get a little bit more specific as well with the rheumatologic workup, antinuclear antibody, rheumatoid factor as well as a more thorough investigation for infectious disease.

06:24 I might throw TB testing into my initial lab, particularly if there’s a risk there.

06:28 As our case – he actually could deserve a TB test as well.

06:34 And then testing for, as I mentioned, CMV, EBV and never forget HIV which is going to present more with an acute illness during the initial stage of infection.

06:44 If you're really stuck at that point and nothing is coming back positive, that’s time to think about looking for that hidden abscess and that can involve a CT scan or an ultrasound.

06:57 And during this time, as you will be seeing patients back in clinic again, sometimes it takes two or three visits, but then you finally find it.

07:06 You trip over something or the patient reveals that there is something in addition.

07:12 There was an exposure, they weren’t vaccinated, they have some kind of sick contact or another symptom.

07:17 So, don't just use the lab to diagnose patient.

07:21 Continue to talk to the patient and work through that history because there might be something that was missed, and that’s going to help you cinch the diagnosis.

07:30 You might need to do some specialized testing as well.

07:32 I would probably leave this for the infectious disease folks, but if they have a change in their levels of cryoglobulins, could indicate either chronic infection or malignancy.

07:42 Thyroid function may need to be assessed as well as complement levels and a serum protein electrophoresis for potential malignancy and looking for monoclonal spikes in antibody levels too.

07:54 But that's probably in the realm of the specialists.

07:56 What has been done, but is discouraged overall, is just the routine application of – you know, I don’t know what this fever is but I’m just going to go ahead and treat you with these antibiotics.

08:07 I’m going to treat you with this round of prednisone.

08:10 That's actually discouraged because it may mask the symptoms without finding a more dangerous diagnosis.

08:16 But what I would encourage you to do is, if really stuck with a patient with documented fevers and despite those steps and going through the history and understanding the differential, going through the lab and the imaging studies, nothing is coming back and yet the patient is really suffering, I would think about admitting that patient and getting an infectious disease consult sooner rather than later to avoid any sequela before it gets too late in the process of either infection, malignancy or the rheumatologic disease.

08:49 And hopefully, that was really helpful to you and you stay well.

08:52 Cheers.