0:00

Now I know last week when we started

0:02

talking about gout and crystals, it brought about

0:04

imagery of people who are trying to sell

0:06

you various things on social media that are

0:09

going to help you manifest all kinds of

0:11

things. Try this gemstone and it'll help you

0:13

gain money. Put this stone in your car

0:15

and it'll help your car run better. All

0:18

of that stuff is nothing more than just

0:20

hocus pocus. But when I talk about crystals,

0:22

for many of us it also brings up

0:24

thoughts of science fiction, especially the Sorcerer's Stone

0:27

and of course Harry Potter. And no, we're

0:29

not going to be talking about Nicholas Flamel

0:31

this week. What we're going to be discussing

0:33

is the role of crystals once again. Now

0:36

this is our next episode in the Crystals

0:38

series. Last week we talked about those negatively

0:40

birefringent needle-shaped crystals in gout. This week we're

0:42

going to be talking about the clinical manifestations

0:45

of calcium pyrophosphate crystal deposition. In other words,

0:47

pseudogout. So there's gout and then there's pseudogout.

0:49

I'm Dr. Niket Sonpal, your friendly-neighbor internist and

0:51

gastroenterologist. So let's kick off that music. I

0:54

wonder if Justin Bieber listens to this podcast.

0:56

Maybe he can remix it for us. That's

0:58

okay. Play it anyway. Now

1:14

when I mention pseudogout to people, they think we're

1:16

crazy in healthcare. We've got one disease that's

1:18

gout and it affected kings and now it's

1:20

affecting regular people. And then we decided to

1:22

name something pseudogout. Well the term isn't

1:24

as commonly used anymore. The term calcium

1:27

pyrophosphate crystal deposition is the appropriate term

1:29

for the disease. Calling it pseudogout is

1:31

just a little bit easier. So

1:34

how common is pseudogout if regular gout is

1:36

not that common to begin with? Well calcium

1:38

pyrophosphate disease is estimated to affect about 4

1:41

to 10% of the populations in

1:43

Europe and the United States. What we know is

1:45

that it gets worse as we get older in

1:47

age. In fact, the prevalence

1:49

of finding calcium pyrophosphate disease on radiographs

1:51

actually increases significantly. They looked at one

1:53

study that looked at people between 65

1:55

and 75. It

1:57

was about 15%. And 75% to

2:00

85, 36 percent. And in

2:02

more than 85 years of old age, well,

2:04

it was about 50 percent. Now we know

2:06

it's not more common in men or more

2:08

common in women. It's actually pretty equal unlike

2:10

regular gout. And there are some ideas of

2:12

why it occurs. We know it has something

2:14

to do with chondrocytes and a lot of

2:16

calcium crystal deposition. It's a theory, but let me

2:19

get into it. Now the exact

2:21

mechanism is not totally understood. We know

2:23

that increased breakdown of ATP, that's right,

2:25

the energy for all things is actually

2:27

increasing pyrophosphate levels in the joints. That's

2:30

because joints move a lot and that

2:32

could be one reason why crystals develop.

2:34

We also know that there's a gene

2:36

called the ANKH gene that's also involved.

2:39

And when you put all these factors

2:41

along with some idiopathic things, we don't

2:43

totally understand right now along with trauma

2:45

and some metabolic and endocrine disorders that

2:48

are very commonly associated specifically hemochromatosis and

2:50

hyperperiferidism, it actually leads to

2:53

calcium pyrophosphate crystal formations in

2:55

the chondrocytes. Then what

2:57

ends up happening is that you

2:59

end up getting excessive cartilage pyrophosphate

3:01

production. This leads to supersaturation. When

3:04

you get supersaturated areas, crystals form,

3:06

deposit, and then start beating up

3:08

on the joints. And that, my

3:10

friends, is calcium pyrophosphate crystal deposition

3:12

disease and what we like to

3:14

call pseudo-gout. Now many of

3:16

you are like, well that's great. I really

3:18

don't care about the pathophysiology, especially if it's

3:20

just a theory and we don't totally understand

3:23

it, and especially if most causes are idiopathic.

3:25

So how are these patients going to present?

3:27

Well, let's kind of go over it. First

3:29

of all, you're going to have some patients

3:31

who are just simply asymptomatic. They may have

3:33

some chondrocalcinosis that are found on x-rays and

3:36

they're just found incidentally. And there are going

3:38

to be other patients who are going to

3:40

actually present like Al, where they're going to

3:42

have self-limited acute or subacute attacks of calcium

3:44

pyrophosphate crystal arthritis. So let's talk about how that's going

3:46

to present. You see, the presentation

3:48

and the actual clinical manifestations of how pseudo-gout

3:51

presents is why it got that name. It

3:53

presented identically to gout, and so everyone thought

3:55

it was uric acid. But then, when they

3:57

looked at the crystals, it was a little

3:59

bit of a bit different. So

4:01

they would present with severe acute inflammation in

4:03

the joint, it wouldn't move well, it was

4:05

painful to move, there was intense pain, just

4:08

throbbing, redness, warmth, and a lot of swelling.

4:10

The knee actually is where it differs. It's

4:12

actually affected in over 50% of

4:14

cases, whereas when we talked about in

4:17

gout, it's the first big toe or

4:19

the metatarsophalangeal joint. The other major difference

4:21

between gout and pseudogout is that calcium

4:23

pyrophosphate disease actually lasted longer for one

4:25

to two weeks. And when you see

4:28

a patient who comes in with knee,

4:30

wrist, elbow, or shoulder pain as their first

4:32

attack, you want to start thinking calcium pyrophosphate

4:34

over gout, but remember like we talked about

4:36

last week, these are just the most common.

4:38

Now you might be thinking that's

4:41

a lot of overlap. Well, there's some

4:43

more. Now you know that there's chronic

4:45

gout, well there's also chronic calcium pyrophosphate

4:47

crystal deposition disease, and it's called pseudo-rheumatoid

4:50

arthritis. Now what the reason for that

4:52

is basically there's morning stiffness, fatigue, edema,

4:54

and restricted joint motions. Patients

4:57

who also have osteoarthritis with calcium pyrophosphate disease

4:59

can also manifest another form of it in

5:01

which they have long-term osteoarthritis with joint breakdown,

5:03

and it's most commonly in the knees followed

5:05

by the wrists. However, for the purpose of

5:07

this podcast, we're primarily going to be talking

5:09

about patients who have acute calcium pyrophosphate deposition

5:11

disease and what to do next. So at

5:13

this point, you know how they're going to

5:15

present. They're going to look identical to the

5:17

patients who have gout. Instead of the big

5:19

toe, it's going to be the knee. But

5:21

what are you going to do about it

5:23

in terms of diagnostics? Well, let's jump into

5:25

it. Now if you remember your

5:28

basics of radiology, you remember that calcium

5:30

things light up like Christmas tree lights

5:32

on an X-ray. Well, it turns out

5:34

that here, it's the same case. But

5:36

that conjo-calcinosis in terms of diagnostic evaluation

5:38

and using conventional X-rays isn't going to

5:40

be your best initial test. Your best

5:42

initial test is going to be the

5:44

clinical findings and features that are going

5:46

to be what we talked about before,

5:48

but the most accurate test, believe it

5:50

or not, is a joint arthrocentesis. Yep,

5:53

that's exactly right. You're going to do

5:55

a synovial fluid analysis. And what you're

5:57

going to look for are going to

5:59

be the findings of calcium. calcium pyrophosphate

6:02

crystals which are actually now positively birefringent

6:04

on compensated polarized light microscopy. In addition

6:06

to that, the white blood cell count

6:08

can range from 10 to 150,000 with

6:10

a nucleophilipid

6:12

dominance, so white counts are pretty unhelpful. The

6:14

other basic reason of why you want to

6:16

do an actual joint tap is because you

6:18

want to rule out needle-shaped crystals and make

6:20

sure that it's actually not gout. You

6:23

see, the calcium pyrophosphate crystals are harder

6:25

to find. The reason why is because

6:27

they're actually pretty small. They're actually weakly

6:29

positively birefringent or not birefringent at all,

6:31

unlike the actual gouty ones which are

6:33

negatively birefringent and light up like crazy.

6:35

And they're also rod-shaped and rhomboid form.

6:37

Some even say they look like little

6:39

envelopes. It's cute, right? But the fact

6:41

of the matter is, is you're looking

6:43

for these different types of crystals. Once

6:45

you have it, you've got your patient's diagnosis. Now

6:48

you might be thinking, but hey, cartilage is

6:50

calcified. Shouldn't we do x-rays? Well, it turns

6:52

out that you can actually use x-rays to

6:55

look for degenerative joint diseases and to see

6:57

if they have any chondrocalcinosis. But remember, it's

6:59

going to be a clinical diagnosis supported by

7:01

the most accurate test, which is joint tap.

7:03

Then you're going to support your diagnosis with

7:06

diagnostic imaging to see if there's any joint

7:08

breakdown and if you need to continue to

7:10

monitor the patients for any involvement in those

7:12

areas. Now, at this point, you've

7:14

pretty much got your diagnosis set. You know

7:17

that this person is dealing with an acute

7:19

crisis of calcium pyrophosphate crystal arthritis. And so

7:21

now you've got to start helping them with

7:23

some symptomatic relief and anti-inflammatories to help them

7:26

get through this episode. The first thing you're

7:28

going to recommend is an application of ice

7:30

or cool packs to the affected joints and

7:32

then rest the area for three to four

7:34

days. This is going to involve things like

7:37

removing weight-bearing activity, maybe even immobilization, and possibly

7:39

even elevating the limb or the joint that's

7:41

affected. Now you'll notice we don't do a

7:43

lot of that with regular gout. And the reason why

7:45

is because this can be a bit longer of an

7:47

extended course. Once that's taken care of

7:49

and you've done your joint aspiration and you've confirmed

7:52

that this is not a septic joint, what you're

7:54

really worried about here is actually a crystal arthritis.

7:56

Your next step is to ask yourself, well, how

7:58

many joints are affected? According to the

8:01

current guidelines and algorithms that are proposed, it

8:03

actually says that if it's one or two

8:05

joints, and these are the kind of joints

8:07

that can get arthrocentesis and an injection of

8:09

glucocorticoids, then you want to go ahead and

8:11

do that and inject the joints. If there

8:13

are hard joints to use, or there's multiple

8:15

joints, like if it's a knuckle or something,

8:17

then you probably want to avoid injecting steroids,

8:19

and then you want to ask yourself, well,

8:21

hey, can this patient take some oral medications?

8:23

And then you have the options of using

8:25

either colchicines, NSAIDs, or glucocorticoids. There isn't really

8:27

a lot of great evidence to decide which

8:29

one is going to come first, but there

8:31

is a little bit of an algorithm that

8:33

helps you say, well, what to do if

8:35

these don't work and what comes next? Now,

8:38

if the patient, for some reason, is unable

8:40

to take oral medications, and they're of that

8:42

variety where they also can't get joint injections,

8:44

let's say it's multiple joints, then these patients

8:46

are that subset of population that are going

8:48

to require either IV or intramuscular glucocorticoids, but

8:50

again, that's a rare circumstance. The majority of

8:52

your patients are going to have a single

8:54

joint, you're going to aspirate, make sure it's

8:56

calcium-powered phosphate disease, that's not a septic joint,

8:59

and you're probably going to inject with some

9:01

steroids. If, however, they have some recurrence or

9:03

multiple, multiple joints affected, then you're probably going

9:05

to try them on either colchicine, NSAIDs, or

9:08

oral steroids. Now, I know what

9:10

you're going to say, well, what if those

9:12

agents don't work? Well, let's say you injected

9:14

the joint. If it didn't work or they're

9:16

still having ongoing persistent symptoms or it's worsening,

9:18

then you can try one of the three

9:20

medications. If they've taken colchicine and it's not

9:23

working, switch to NSAIDs or add on oral

9:25

glucocorticoids. If you gave them NSAIDs, then add

9:27

on colchicine or switch to the oral steroids.

9:29

And if you gave them oral glucocorticoids and

9:31

it's not working, you can add on colchicine

9:33

or you can switch the route of how

9:36

you give the glucocorticoids and add on colchicine.

9:38

Now, if you have one of those

9:40

patients who has pretty severe refractory symptoms

9:42

and they can't take oral medications and

9:44

you've tried intravenous glucocorticoids and you've tried

9:46

everything, then these are some patients who

9:48

are going to want to try to use

9:50

the interleukin-1 inhibitors like anakinra. The good

9:53

news is that it's rare to have disease that's super

9:55

refractory. Most patients start to feel better within 48 to

9:57

72 hours of initiation. Now

10:00

what if you have a patient who comes in and they

10:02

tell you, well I've had three or more attacks of this

10:04

pseudo-gout. What have I got to do? For

10:06

these patients, you're going to start them on prophylactic

10:08

therapy. We talked about it with a regular gout

10:11

where they're going to get alopurinol or one of

10:13

the other medications. When it comes to pseudo-gout, they

10:15

get prophylactic therapy with colchicine. This is going to

10:17

be started if they have more than three episodes

10:20

a year. Now if they can't

10:22

tolerate colchicine, let's say they have a contraindication

10:24

to it, or they're just intolerant of it

10:26

because of the ongoing diarrhea. Remember what I

10:28

told you guys last week, when patients used

10:30

to get colchicine back in the day and

10:32

we didn't have standardized pills, they would take

10:34

enough until they developed diarrhea. That was the

10:36

therapeutic dose. But the alternative agent, if you

10:38

can't tolerate the actual colchicine, is going to

10:40

be NSAIDs. Now the last

10:43

little bit of care when it comes

10:45

to calcium pyrophosphate disease is to remember

10:47

that even though most people have idiopathic

10:49

forms, if they have some associated diseases

10:51

like let's say hyperparathyroidism, or let's

10:53

say for example hemochromatosis, you also want

10:55

to get them to those disease modifying

10:58

treatment algorithms and get them to the

11:00

right consultants to manage those diseases as

11:02

well. Because treating them is just as

11:04

equally as important as treating the chronic

11:06

and acute calcium pyrophosphate disease. And

11:09

with that, ladies and gentlemen, brings us to the end of

11:11

this podcast. I'm Dr. Nick Hessenpaul, your friendly neighborhood

11:13

internist and gastroenterologist, and that brings us to

11:15

the end of this series on crystal. I'll

11:17

see you next week. Thank

11:27

you.