Icm Rheum 3: Crystal Induced Arthropathies

Front 1

what criteria must be met to have gout?

Back 1

*Supersaturation of uric acid in the blood (>level of 7) followed by…
*Extracellular deposition of uric acid crystals in the synovium of joints, bursae and/or tendons followed by..
*Release of crystals into joint or bursae with accompanying inflammation

Front 2

do patients w/ gout have hyperuricemia?

Back 2

All patients with gout have hyperuricemia at some point

Front 3

if you have hyperuricemia, do you get gout?

Back 3

Hyperuricemic individuals do not necessarily ever develop gout

Front 4

if someone comes in w/ hyperuricemia, can you diagnose them w/ gout?

Back 4

No! Diagnosis of gout requires tissue deposition of urate crystals and accompanying inflammatory consequences.

Front 5

what does the outside of the spot of body w/ pain look like?

Back 5

Acute inflammation with pain, redness and swelling.

Front 6

when is max severity reached in gout? resolves when?

Back 6

Maximal severity reached over several hours
resolves in 3-10 days.

Front 7

where does gout affect ppl?

Back 7

80% of initial attacks involve a single joint, typically in the lower extremity (1st MTP)

Front 8

does inflamm stay confined to joint in gout?

Back 8

Inflammation can spread beyond joint giving tenosynovitis (mimics cellulitis)

Front 9

are there urate (uric acid) crystals in synovial fluid when having inflammation?

Back 9

YES!

Front 10

how do you diagnose acute gouty arthritis?

Back 10

Joint aspiration is required.
Hyperuricemia and joint effusion not enough.
look at fluid under polarized microscope

Front 11

what can acute gouty arthritis mimic?

Back 11

can mimic septic arthritis with fever, leukocytosis and high sedimentation rate

Front 12

what does it mean to have inflammation?

Back 12

>2000 WBC

Front 13

what disease do these crystals deposit in? monosodium urate monohydrate crystal deposion

Back 13

gout!

Front 14

what disease do these crystals deposit in: calcium pyrophosphate dihydrate crystal deposition

Back 14

CPPD crystal disease (pseudogout)

Front 15

what does gout look like under microscope? pseudogout?

Back 15

gout- thin, pointy crystals
pseudogout- rhomboids!

Front 16

when under the polarizer, you see parallel and perpendicular gout, what's the color?

Back 16

parallel- yellow
perpendicular- blue

Front 17

when under the polarizer, you see parallel and perpendicular pseudogout, what's the color?

Back 17

parallel- blue
perpendicular- yellow

Front 18

how many crystals do you need to find in PMNs to make gout diagnosis?

Back 18

1

Front 19

can gout appear lumpy?

Back 19

yes! can get big lumps of uric acid all over if has been going on long time

Front 20

what color is a urate crystal when parallel to the plane of polarization?

Back 20

yellow!

Front 21

When a joint is warm and swollen, is the presence of hyperuricemia adequate to make the diagnosis of gout?

Back 21

NO!!

Front 22

When gout first appears, a typical flare lasts how many days?

Back 22

3-10 days

Front 23

what are the risk factors for gout?

Back 23

Hyperuricemia
Increasing Age
Male sex
Hypertension
Obesity
Hyperlipidemia

Front 24

what's the disease course of gout?

Back 24

1-Asymptomatic hyperuricemia with supersaturation of the blood
2-Crystal deposition in the synovium and periarticular tissues
3-Release of crystals into synovial fluid with resultant inflammation and acute gout
4-Possible progression to chronic tophaceous gout

Front 25

how much urate is resorpted by kidney?

Back 25

80% of resecreted urate

Front 26

how much is excreted by kidney?

Back 26

~10% of filtered load

Front 27

most of hyperuricemia is b/c of what? lesser % is b/c of what?

Back 27

90% of cases are secondary to underexcretion
10% of cases are secondary to overproduction

Front 28

how do you figure out if someone is underexcreting or overproducing to have hyperuricemia? what's normal?

Back 28

24 hour urine uric acid will help to define pathophysiology
Normal = 600-1000mg over 24 hours

Front 29

The higher the serum uric acid and the longer the hyperuricemia, the greater the chance of developing ____________

Back 29

gout

Front 30

what are the causes of hyperuricemia secondary to underexcretion?

Back 30

Dehydration, starvation or ketosis
Drugs: diuretics, low-dose aspirin, ethanol, cyclosporin, ethambutol, nicotinic acid
Toxins: ethanol and lead
Hypothyroidism, hyperparathyroidism, sarcoidoisis, obesity.
Chronic kidney disease --> inc creatinin

Front 31

what are the causes of hyperuricemia secondary to overproduction?

Back 31

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency
Overactive phosphoribosyl pyrophosphate (PRPP) synthetase
Myeloproliferative diseases
Psoriasis
Chemotherapy
leukemia, lymphoma
Downs syndrome, glycogen storage disease, obesity, excessive purine ingestion

Front 32

if someone is undergoing chemotherapy, what other med do you give them?

Back 32

allopurinol so they don't get gout

Front 33

what enzyme is overactive in gout?

Back 33

PRPP synthetase

Front 34

what enzyme is underactive in gout?

Back 34

HGPRT

Front 35

what enzyme does allopurinol act on?

Back 35

xanthine oxidase
xanthine --X--> uric acid

Front 36

What percentage of patients with gout underexcrete?

Back 36

90%

Front 37

How do you determine whether someone underexcretes?

Back 37

24 hour urine uric acid test

Front 38

what factors can precipitate a gout flare?

Back 38

Trauma
Surgery or hospital admission with IV fluids
Starvation
Dehydration
Increased alcohol consumption (beer and spirits, not wine)
Dietary indulgence: esp. inc purine in diet
Acute changes in serum uric acid level
Stopping or starting medications for gout
Uric acid can be artificially low if hydration

Front 39

once on allopurinol, when do you stop taking drug?

Back 39

never stop!
unless what caused gout went away
ex: leukemia goes into remission, you can get off of allopurinol

Front 40

describe factors of crystal induced inflammation:

Back 40

Crystals in synovium released into joint
IgG and complement attach to crystals
PMNs phagocytose crystals
Release cytokines causing
Inflammation
Synovial effusion with high WBC count
Fever
Attack resolves in days

Front 41

in crystal induced inflamm, Deposited/dispersed crystals reach what area?

Back 41

synovial fluid

Front 42

what's this IgG and complement attach to crystals mediated by?

Back 42

opsonization

Front 43

Phagocytosis by, lysis of PMNs releases pro-inflammatory mediators and chemokines which causes?

Back 43

vasodilation, swelling, effusion, erythema, pain
influx of PMNs creates + feedback loop

Front 44

in gout crystal induced inflamm, how many WBC?

Back 44

Synovial fluid WBC INC to 10-80,000 WBC/mm3

Front 45

which cytokines are involved in GOUT inflamm? what's the result?

Back 45

(TNF, IL-1, IL-6) can include fever, INC acute phase reactants

Front 46

what helps limit acute inflammation?

Back 46

Lipoproteins on crystals

Front 47

how does gout inflammation resolve? when?

Back 47

Attack resolves spontaneously after days-weeks without apparent joint damage or contracture

Front 48

After 1st attack there is:

Back 48

“intercritical gout period”.

Front 49

Most untreated patients will have a second episode within

Back 49

2 years

Front 50

if untreated, get:

Back 50

additional acute attacks
progressively shorter asymptomatic periods
increasingly severe, prolonged and polyarticular. flares

Front 51

if start someone with gout on gout meds, can they have a gout attack?

Back 51

yes! b/c change in uric acid level! must also put them on nonsteroidal drug

Front 52

does gout ever spread?

Back 52

as more time passes after having gout: chronic
Eventually gout presents in multiple joints at once
Also can involve tendons and bursae.
Bony erosions and deformities with recurrent attacks

Front 53

what can urate deposits cause?

Back 53

cause tophi on extensor surfaces

Front 54

what's acute gout tx?

Back 54

Aspirate and make diagnosis
Treatment depends on the patient:
Non-steroidal anti-inflammatories (NSAIDs)
steroids (po, intrarticular or IV)
oral or IV colchicine
Narcotics
Rest
IL-1 antagonists

Front 55

what should person do after 1st attack?

Back 55

Modify medications
Reduce alcohol intake
Lose weight
Medications to increase excretion (if underexcretor)
Medications to reduce production (allopurinol, febuxostat and PEG-uricase)

Front 56

can someone have gout flare w/ low serum uric acid?

Back 56

YES! if change in hydration, like from IV fluids for ex

Front 57

is there a correlation b/w lowering urate levels and tophi reduction?

Back 57

yes! looks linear! as urate dec, tophic dec

Front 58

Large accumulations of uric acid around the olecranon bursae are referred to as ______.

Back 58

tophi

Front 59

what's this: Calcium Pyrophosphate Dihydrate Crystal Deposition Disease (CPPD)?

Back 59

pseudogout

Front 60

where do CPPD crystals deposit?

Back 60

joint articular cartilage (hyaline)
fibrocartilage (menisci)
ligaments

Front 61

does pseudogout always have symptoms?

Back 61

no! may be asymptomatic

Front 62

what's chondrocalcinosis?

Back 62

is an xray diagnosis
XRay shows calcification of the articular cartilage and fibrocartilage
calcification is from CPPD crystals
*cartilage white instead of black

Front 63

if CPPD CRYSTALS released into joint causing acute inflammation this is termed ____________

Back 63

pseudogout

Front 64

what's the diff b/w urate and CPPD crystals?

Back 64

Monosodium urate (Gout)
Needle-shaped, about size of PMN
Negatively birefringent
Calcium pyrophosphate dihydrate (Pseudogout)
Rhomboid, smaller than PMN
Positively birefringent
CPPD-DD

Front 65

what are the most common joints involved in CPPD?

Back 65

Knee: meniscus, patellofemoral joint
Wrist: triangular fibrocartilage in distal radioulnar joint
Elbow
Shoulder
Ankle
Acromioclavicular
Hip

Front 66

WHAT causes CPPD formation?

Back 66

Extracellular ATP "scavenging" by nucleoside triphosphate pyrophosphate hydrolase yields PP
OA cartilage matrix abnormal, favors Ca + PP crystal deposition

Front 67

what are the symptoms when there's crystal release of CPPD?

Back 67

pseudogout
joint effusion with little or no pain
chronic "RA-like" arthropathy

Front 68

WHAT are big risk factors for CPPD?

Back 68

INCREASING AGE
OA

Front 69

WHAT are the symptoms for pseudogout?

Back 69

Acute or subacute episodes of joint inflammation that last form 1 day to several weeks.
Usually monoarticular but can be migratory.
Knee>wrist> elbows> shoulder>ankle.
CPPD can be asymptomatic or have small painless knee effusions.

Front 70

how do you diagnose pseudogout?

Back 70

Like gout, fluid aspiration is required.
Fluid tends to be inflammatory (greater than 2000).

Front 71

When CPPD crystal are in the cartilage and seen on plain xray that is called ________.

Back 71

chondrocalcinosis

Front 72

Name the shape of CPPD crystal when seen under polarization.

Back 72

rhomboid

Front 73

Name 2 joints that are most commonly associated with pseudogout:

Back 73

knee
wrist

Front 74

what's the etiology of CPPD deposition?

Back 74

Idiopathic: increasing age
Frequently seen with osteoarthritis
Hereditary: autosomal dominant inheritance
Metabolic Disease:
Hyperparathyroidism
Hypothyroid
Hemochromatosis,
Hypomagnesemia
Hypophosphatemia,

Front 75

what are the X-ray findings of CPPD?

Back 75

Choncrocalcinosis
Subchondral cysts
Beak-like projections 2nd and 3rd metacarpal heads

Front 76

WHAT'S the is most common BCP (basic calcium phosphate) crystal?

Back 76

hydroxyapatite

Front 77

can hydroxyapatite crystals cause chondrocalcinosis?

Back 77

YES!

Front 78

are the amorphous hydroxyapatite crystals visible w/ polarized light?

Back 78

no!

Front 79

how do you see hydroxyapatite (BCP) crystals under the microscope?

Back 79

Requires special stain (Alizarin red) to see under microscope

Front 80

what can hydroxyapatite crystals lead to?

Back 80

Leads to cartilage and bone damage with chronic low grade inflammation

Front 81

what are the WBC counts in synovial fluid of hydroxyapatite crystals?

Back 81

Synovial fluid WBC counts typically 1k

Front 82

what are hydroxyapatite crystals ass w/?

Back 82

Associated with periarthritis, tendon calcifications

Front 83

what's most commonly affected by hydroxyapatite crystals?

Back 83

Shoulders and knees most commonly affected

Front 84

what are the symptoms of hydroxyapatite crystals?

Back 84

Can have an acute onset of pain and swelling or be a chronic low grade inflammation
Role in progressive rotator cuff degeneration
Elderly women can have a “Milwaukee Shoulder” associated with this progressive destructions. Fluid has BCP crystals

Front 85

what are the triggers for CPPD?

Back 85

Joint Trauma
Medical Illness
Surgical Procedure

Front 86

WHAT'S pseudogout TX?

Back 86

Acute pseudogout can be treated in a number of ways:
Aspiration of the joint with injection of steroids
Oral nonsteroidal anti-inflammatory drugs
Oral colchicine
Oral steroids
Oral nonsteroidals or colchicine can also be used to prevent future flares, as in gout therapy.