So, we’re going to be
discussing fever in adults now.
when you think about fever,
particularly among adults or kids,
it’s usually do to a virus,
We’re going to dig a little bit
deeper into causes of fever among adults,
including some non-infectious causes.
So, I’m going to start with a case.
I’ve got a 40-year-old man
who complains of fever
for the past four weeks.
That’s a long time.
He recently returned from a trip
and is worried about
his infectious disease,
as am I.
So, it turns out he returned from Central Africa
and he measured his temperature once.
It was 38°.
His only other symptom is
fatigue and myalgia.
He has a history of gout.
He takes allopurinol and naproxen.
He’s tried a course of amoxicillin that he
left over from a previous sinus infection
because nobody ever throws
away their drugs ever.
He found that three days of treatment
didn't improve his symptoms at all.
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,
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.
Not in this guy.
I’d be surprised if he
doesn’t have malaria.
Therefore, he needs a pretty broad workup
and he may not have malaria.
He may have some other tropical diseases.
Therefore, the blood culture
and the broader workup are necessary as well.
So – and we’ll talk about workup
for fever of unknown origin shortly.
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.
Now, I think it’s a more modern definition,
which is more patient friendly.
Fever measured at multiple times
and there's been adequate
workup either in the outpatient
or the inpatient setting.
So, therefore, that broadens
the number of patients
who might be defined as having FUO.
What’s the differential?
So, it comes down to
infection in 20 to 40% of cases.
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.
Abscesses can hide and be walled off,
but occasionally produce
inflammation and hence fever.
Classic for endocarditis as well.
Another place that bacteria can hide.
And then tube viruses
bear noting that produce symptoms –
an infection fairly frequently,
or Epstein-Barr virus.
Both of these are pretty common
and both can cause
symptoms over a period of weeks,
And so, you may want to
think about specific testing for those viruses,
and that's part of the workup I’ll get to.
Malignancy, 20 to 30% of cases of fever
of unknown origin are due to malignancy.
Inflammatory diseases promote
up to 30% of these cases as well.
And it’s a pretty broad list of most
of the major inflammatory diseases –
systemic lupus, sarcoidosis,
and temporal arteritis.
All of these can promote fever.
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.
So, there's lots of ground to cover.
each of these disorders,
beyond the fever,
comes with associated characteristics
that can help you identify it more readily.
There are other causes including
medications which we’re going to go over.
And up to 50% of cases,
there is no actual cause found
for the fever after workup.
Factitious fever is rare,
but patients will sometimes
use it as a way to get attention.
Munchausen syndrome, for example.
Thyroiditis can promote a fever
as well, as can thrombosis.
And then as I mentioned,
medications may account for up to 3% of
cases of intermittent and prolonged fevers.
There it is.
Those are unknown.
I got it.
So, what kind of medications promote fever?
Phenytoin, carbamazepine can do it.
H2 receptor antagonists such as ranitidine
and cimetidine also can be implicated.
sulfonamides with penicillins.
And cardiovascular drugs like
hydrochlorothiazide which I use a lot.
And NSAIDs too,
which we use to treat fever are
very rarely associated with fever.
So, is it common to see fever
with any of these drugs?
Should you avoid them
because of the risk for fever?
They are generally good drugs.
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.
These drugs should be considered.
In terms of the workup,
initial laboratory work includes what you see there.
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.
If that's all negative,
a more thorough
investigation is necessary.
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,
as well as a more thorough
investigation for infectious disease.
I might throw TB testing
into my initial lab,
particularly if there’s a risk there.
As our case –
he actually could deserve a TB test as well.
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.
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.
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.
You trip over something or the patient
reveals that there is something in addition.
There was an exposure,
they weren’t vaccinated,
they have some kind of sick
contact or another symptom.
So, don't just use the
lab to diagnose patient.
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.
You might need to do
some specialized testing as well.
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.
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.
But that's probably in the
realm of the specialists.
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.
I’m going to treat you
with this round of prednisone.
That's actually discouraged
because it may mask the symptoms
without finding a more dangerous diagnosis.
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.
that was really helpful to
you and you stay well.