So let's go back to our case and see if he
has any of those particular risk factors.
So, his age is 51 and he's a man.
Those are classic symptoms or classic
features that may go along with gout.
HIV, a chronic inflammatory state.
That's gonna potentially contribute
to increased purine synthesis.
He's got hypertension,
we talked about that.
CKD, he's clogging the drain.
He's obese, that's a factor.
He's on a diuretic, everything's
going for gout for this guy.
And of course, he has
a history of gout.
So enough things on the page
that will help us to say
that gout is a very likely contributor
to what could be going on for him.
Now the thing that's unusual about our
patient is the fact that he's telling us
that he has 2 joints involved and that his
symptoms evolved over the span of over 5 days.
And we looked at that picture before
of a rat, biting unto somebody's toe
and that was a monoarticular gout
and was a very acute onset .
So what's the deal with this guy
having multiple joints involved
and at being a more protracted
kind of evolution overtime.
So in order to answer that question, we have
to understand the natural history of gout.
Starting here on the far left of
this schematic is hyperuricemia.
It turns out that a person
kind of have hyperuricemia
with a level of uric acid in the
bloodstream greater than 7.0 ng/dl
for about 10 years potentially
before they have their first gout flare.
Once they've had their first gout flare,
which would typically be monoarticular,
there's a 60% chance they will have
a recurrence within the next year.
With each subsequent recurrence, the time
between recurrences get shorter and shorter
as shown here by the bars of
recurrence time point over time.
And in addition, each recurrence
is more likely to be prolonged
with a more gradual onset
and a longer phase of recovery.
And also, you are more likely
to have polyarticular flares.
Our patient has an oligoarticular
flare but overtime if the disease
continues to be untreated, he may start to have
5, 10 different joints involved at a time.
With another 10 years of time,
you can start to develop tophi.
Tophi are these tophaceous deposits in the joints
that are basically just uric acid crystal deposition
that can be palpable on
the skin or around a joint.
And of course, chronic arthritis with
some erosive changes being found as well.
So actually, his story of having gout for a long
time and having this oligoarticular presentation
and a slow onset of symptoms is pretty
typical for untreated or prolonged gout.
So, this is actually a pretty typical
story of a patient who has chronic gout
and all of these symptoms could
really be explained by that.
However, it's important for us to
exclude some potential other pathologies,
most notably, septic joint.
Something you just can't miss.
So, I think we're gonna have
to perform an arthrocentesis
In this case, nothing's easier
than tapping the right knee.
It's a very large joint, easy to get some fluid
from, so let's do that and see what we get.
Okay, so here's our
Many negatively birefringent
I wonder what that means.
So here we see negatively
This is basically monosodium urate which
forms crystals when they deposit in fluid.
In this case you can see that
they are negatively birefringent
which means shining depolarized light in one
direction will have a yellowish, orange coloration.
Whereas on the other direction, the blue crystals
that are on the side are highlighting in blue.
That's a characteristic feature
of monosodium urate crystals
and is different than some of the other types
of crystals which can deposit in joints.
So, in addition from our arthrocentesis, we see
that he has a few blood cells, 55,000 neutrophils.
The number of neutrophils
is also important.
On this schematic here, just highlighting how the number
of white blood cells found in the arthrocentesis fluid
may help to guide us towards thinking about different
types of conditions that afflict the joints.
If you have less than 2,000 cells, we're
thinking about non-inflammatory causes,
osteoarthritis would be good example.
A rheumatologic idealogy may be reactive
arthritis or lupus or something like that.
2,000-20,000 would be a typical
number of cells to be found in such a joint.
Gout can be a wide range, about 20 to maybe 80,000
cells would be pretty typical for a gout flare.
And then if you've got more than 80,000 cells
in a joint, maybe even over a 100,000 cells,
then you really should be
worried about septic joint.
So in our case, our patient's got about 50,
that's pretty typical for acute gout flare.
It probably makes sense at this point that take a step
back and ask, "Why are those cells in the joint?"
This is the concept of crystal
That is uric acid crystals cause an
inflammatory cascade within in a particular joint.
How did the crystals end up in that joint?
What's the number of extrinsic
factors that contribute to that?
We're thinking about the
general chemistry here.
What causes a particular substance
to crystalize in solution?
Well, these factors are things like the pH of
the solution, in this case synovial fluid.
The temperature, typically lower temperatures are gonna
contribute to crystal supersaturation and crystal formation.
And then dehydration, simply that's gonna affect
the concentration of uric acid in solution.
We think about podagra, again, which most commonly occurs
late in the evening, it's afflicting the great toe
and in the evening, that's when you're
relatively breathing at a slower rate,
so your pH of your blood and of your articular
fluid is gonna be a little bit more acidic,
you're gonna be little bit cooler especially if your
toes are peeking out from underneath the sheets.
And you're also gonna be relatively
dehydrated because you haven't had any fluid
consumed while you've been sleeping.
All those factors contribute to why your first
flare of gout tends to occur in the great toe
while you're asleep at night.
So, uric crystals form and then once they
form they deposit into synovial tissues
and you can imagine having little knives sticking
into your joint's synovial fluid or joint synovium,
that's gonna contribute to
an inflammatory response.
Initially, there will just be a local cell mediated
response with some macrophages and monocytes.
Ultimately, they're gonna recruit large numbers of
neutrophils and then boom, crystal-induced inflammation.
Fortunately, this process also is self resolving
and over time, those neutrophils go away,
inflammation dies down and your typical gout flare
can last 5 to 7 days and go away on it's own.
So, we've got crystals, we've got
neutrophils, sounds like we're done, right?
Always remember that just
because the patient has gout,
that doesn't mean, he doesn't also have septic
We still need to perform a gram stain and
a culture and keep this person on antibiotics
until we get that information back.
A person can have gout and have
an infection at the same time.
So, now we've got some more data, gram stain
is negative, fluid culture has no growth.
Alright, so we should methodically just
go through our list one last time here.
So we can officially take out pseudogout, we have
no evidence of CPPD crystals on the synovial fluid.
We'll talk more about those
crystals in a moment.
Septic joint, that's out.
We got a negative culture from the fluid
as well as a negative gram stain.
Lyme disease, doesn't seem very likely anyway 'cause wh
didn't have any risk factors and doesn't have any skin rash.
So, I think we can safely say that our patient's
symptoms can be fully explained by an acute gout flare.
So, it's gout, now what?
To talk about the treatment of gout, we should
reflect again a little bit on our bathtub analogy.
If we wanna reduce some of the many symptoms
of gout, we have to focus on either first,
managing the acute inflammatory
process and then secondly,
we wanna focus on slowing down the
tap and also unclogging the drain.
In our case, he's having an acute flare, we really
wanna focus on cooling down on the inflammation
before we do anything else.
So, this category down here
is what we want to focus on.
Anti-inflammatories: NSAIDS, colchicine,
systemic steroids or intra-articular steroids.
Now our patient has some CKD.
We have to be a little cautious about using NSAIDS
or cochicine which are both renally excreted.
So in this case, since we know we
can tackle two different joints,
the knee and the ankle, it would be most
pertinent to use intra-articular steroid.
Systemic steroids would be fruitful if it's a very hard
joint to tap or if there's multiple joints involved.
Once we've accomplished that
and cooled down his acute flare,
then we could go back and start talking
about managing the uric acid production
by tackling things like or using things like allopurinol
which is gonna decrease uric acid production.
And on the right hand side, trying to unclog the
drain by promoting uricosuria or urate excretion.
Classic agents like probenecid and sulfinpyrazone
have been shown to increase uric acid excretion.
Those are gonna be medications we'll be using
in a long term to prevent future flares.