Gout

Question 1

WHat are three characteristics of gout?

Answer 1

1. Elevated serum uric acid (hyperuricemia)
   Uric acid > 6 mg/dL
2. Tissue deposition of monosodium urate (MSU) crystals
3. Gouty Arthritis: tender, hot, swollen joint caused by MSU crystals in joints and/or soft tissues

Question 2

what are exogenous causes of increase in purines?

Answer 2

meat
seafood
beer

Question 3

exogenous causes of purines?

Answer 3

fructose

genes

Question 4

what decreases uric acid excretion?

Answer 4

genes
renal impairment
alcohol
diuretics

Question 5

why does gout cause pain?

Answer 5

hyperuricemia –> precipitation of urate crystals in joints –> activates complement–> neutrophils phagocytosis of crystals –> lysis of neutrophils –> release of enzymes

plus -> phagocytosis of monocytes –> release of ILs and TNF in synovium –> release of proteases –> tissue injury and inflammation

Question 6

“non-modifiable” risk factors

Answer 6

Assigned male at birth (or high testosterone? unknown)
Advanced age
Family History

Question 7

Modifiable risk factors

Answer 7

High purine diet (seafood, red meat)
High alcohol intake, esp. beer
Medications (e.g. diuretics, cyclosporine)
Obesity
Hypertension
Cardiovascular disease
Chronic kidney disease

Question 8

what are dietary restrictions and foods to encourage in a person with gout?

Answer 8

Limit:
Organ meats, herring, anchovies, mackerel, red meat, fatty fish and seafood
Alcohol – especially beer
High-fructose corn syrup (sodas and juice drinks)
Saturated fat (lowers ability to eliminate uric acid)

Good to eat:
Low-fat dairy
Fruits and vegetables
Complex carbs

Question 9

what are precipitating factors for acute gout?

Answer 9

Surgery

Alcohol

Diet

Fluctuation of uric acid level
initiation of therapy to lower uric acid level
diuretics

Question 10

When left untreated, what happens with gout?

Answer 10

Get worse, less reduction in symptoms, more frequent exacerbation,
eventually –> chronic tophaceous gout ie urate crystal deposits in tissue

Question 11

Gout DDx

Answer 11

Septic Arthritis

Calcium Pyrophosphate Deposition Disease (Pseudogout)

Gonococcal Arthritis

Rheumatoid Arthritis

Psoriatic Arthritis

Reactive Arthritis

Question 12

important factors for diagnosing gout

Answer 12

Evaluate for typical clinical manifestations of gout
Serum urate level may be normal at time of flare
Uric acid gets consumed by crystal formation
And people with high uric acid levels may never get gout
Gold standard: Synovial Fluid Analysis
MSU crystals are
Needle-shaped
Negatively birefringent
MSU = Yellow = Parallel = Negative

Question 13

Differentiate between gout and pseudogout

Answer 13

gout:

• uric acid crystals
• tophi
• most common is first MTP joint
• negatively bifringent
• needle shaped

pseudogout

• usually affects larger joints such as knee
• chondocalcinosis on radiograph (visible on XR)
• calcium pyrophosphate dihydrate (CPPD) crystals (rhomboid)
• positively bifringent

Question 14

treatment of acute gout flares

Answer 14

Non-steroidal anti-inflammatory drugs (NSAIDs)

Colchicine

Glucocorticoids
Intra-articular
Oral / systemic

Analgesics/Ice

Observation (no therapy)

Question 15

How do you administer cochicine?

Answer 15

1.2 mg (2 tablets), followed by 0.6 mg 1 hour later, then 0.6mg one to two times daily until resolution of symptoms

Works best if used early (within hours) and in monoarticular attacks
Give to patients to have at home when attack starts

Side effects:
Diarrhea
Bone marrow suppression at high doses

Dose adjustments for renal impairment

Question 16

How do you administer glucocorticoids in acute gout flare?

Answer 16

Typical starting dose is prednisone 30-40 mg daily

Taper over 9-12 days
ie, decrease by 10 mg every 3 days

Side effects = hyperglycemia, poor sleep, agitation, and others with long term use

Caution with diabetic patients

Question 17

What are the goals of treating chronic gout?

Answer 17

Reduce serum uric acid levels (< 6.0 mg/dL)
decrease uric acid production (inhibit xanthine oxidase)
increase uric acid excretion (uricosuric drugs)

Question 18

What is allopurinol and how do you administer?

Answer 18

Blocks xanthine oxidase, decreasing the generation of uric acid

Dose starts at 100mg (50mg with renal insufficiency)

Titrate up monthly until uric acid level of 6 mg/dL or less is achieved (many require > 300mg/day)

Question 19

side effects of allopurinol

Answer 19

Rash

GI intolerance (diarrhea, nausea)

Increase in LFTs

Steven Johnson Syndrome – rare but life threatening
Risk elevated in renal impairment but low if dose titrated up slowly

Renal toxicity NOT a side effect!

Question 20

What is febuxostat?

Answer 20

Also inhibits xanthine oxidase

Dose 40 mg or 80 mg daily

Metabolized mainly in the liver: no dose adjustment needed in renal insufficiency

Adverse reactions: LFT elevation, nausea, arthralgia, and rash

Question 21

What are keys to urate-lowering therapy?

Answer 21

Titrate medications:
Monitor uric acid levels every 2-4 weeks and titrate dose until goal < 6.0 mg/dL is reached

Prevent gout flares:
Lowering uric acid often increases the rate of gout flares intially
Prophylactic therapy: NSAIDs, colchicine

During a gout flare, do not start new uric acid lowering therapy or stop therapy someone is on

Question 22

What are gout take-home points?

Answer 22

Gout is common

Elevated uric acid leads to deposition of MSU crystals, causing episodes of debilitating joint inflammation

Definitive diagnosis is based on presence of MSU crystals in aspirated synovial fluid

Treat the inflammation of acute gout attacks

Then lower uric acid to prevent future attacks