Gout

Question 1

What causes gout?

Answer 1

Imbalances in purine metabolism
Deposition of monosodium urate (MSU) crystals in articular and periarticular tissues –> lead to inflammation, swelling, pain –> gouty attack

Question 2

Clinical spectrum of diseases due to gout

Answer 2

• Recurrent acute gouty arthritis (assoc. w urate crystals in synovial fluid)
• Tophi (deposits of monosodium urate crystals in tissue in & surrounding joint) → chronic
• Interstitial renal disease (gouty nephropathy) → extra articular presentations
• Uric acid nephrolithiasis (uric acid kidney stones) → extra articular presentations

Question 3

What dietary and lifestyle factors worsens gout?

Answer 3

Alcohol consumption
Sugary beverages
Red meat
Sedentary lifestyle –> obesity

Question 4

Does gout occur more freq in male or female?

Answer 4

Males

Question 5

What are 2 ways that causes hyperuricemia?

Answer 5

Increased purine/urate production
Decrease uric acid clearance

Question 6

What are some drugs that decrease uric acid clearance?

Answer 6

Diuretics
Levodopa
Cyclosporine nad tacrolimus
Ethambutol
Low dose salicylates
Salt restriction

Question 7

What are presentations of a gout attack?

Answer 7

• Usually monoarticular @ 1st great toe
• wakes up from sleep by pain
• severe pain for severe hours
• swelling and discomfort continues for days to weeks

Question 8

Why does gout attack commonly start from big toe?

Answer 8

Uric acid in cold temp, lowers its solubility causing it to precipitate and since the big toe is furthest from circulatory, it is coldest part of the body

Question 9

Does asymptomatic hyperuricemia suggests gout?

Answer 9

No

Question 10

How to diagnose gout?

Answer 10

Diagnosis based on presence of monosodium urate crystals in…
- Synovial fluid (detected in joint aspirate)
- Tissue sections of tophaceous deposits (Tophi)
- Joint aspiration → from joint fluid then view under microscope to check for birefringent like crystals (needle shape, yellow)

Question 11

How would the joint aspirate look like in gout attack?

Answer 11

Yellow colour and cloudy
Presence of uric acid crystals

Question 12

What is Tx goal of gout?

Answer 12

• Provide rapid, SAFE, & effective pain relief
• Reduce future attacks (reduce SU concentration): do baseline serum urate lvl
• Address associated comorbidities
• Prevent joint destruction and tophi formation
• Increase quality of life

Question 13

What are common pharmacotherapy for acute gout?

Answer 13

Colchicine
NSAID
CS

Question 14

What are common pharmacotherapy for chronic gout?

Answer 14

Allopurinol
Febuxostat
Probenecid

Question 15

What is usually given for 1st line in acute flares?

Answer 15

Colchicine (within 24hrs)

Question 16

What is nonpharm for flares?

Answer 16

Topical ice

Question 17

What is colchicine dose for acute flares?

Answer 17

• One off treatment with 1mg loading dose, followed by 1 dose of 0.5mg 1hr ltr

OR

• 0.5mg 2-3times/day until flare resolves

Question 18

What is NSAID dose for acute flares?

Answer 18

Celecoxib 400mg LD, 200mg 12hrs ltr on day 1 then continue 200mg BD daily thereafter. Max: 400mg/day. Tx duration usually 5-7days

Question 19

What is CS dose for acute flares?

Answer 19

Prednisolone 30-40mg QD or in 2 divided doses for 2-5days or until smx resolves. Then taper down gradually for another 7 days by halving dose then discontinue

Can also dose by weight: 0.5mg/kg

Question 20

Colchicine SE

Answer 20

N/V, diarrhoea

Question 21

Should colchicine and NSAID be cautioned in renal impairment?

Answer 21

Yes.

Consider reducing dose of colchicine.

NSAID is CI in CrCl <30ml/min

Question 22

When should Urate Lowering Therapy (ULT) be initiated?

Answer 22

• Freq acute gout flares (>=2/yr)
• Presence of any tophus
• Clinical or imaging findings of gouty arthropathy
• Hx of urolithiasis

Question 23

What is Tx target for ULT?

Answer 23

Non-thopaceous gout: <6mg/dl
Tophaceous gout: <5mg/dl

Question 24

How does allopurinol and febuxostat help in gout?

Answer 24

Decrease prdtn of uric acid

Question 25

How does probenecid help in gout?

Answer 25

Prevent reabsorption of uric acid which increases uric acid excretion

Question 26

What is the most impt point to counsel for allopurinol?

Answer 26

Risk of SCAR

Question 27

Febuxostat should be used in caution in what conditions?

Answer 27

HF and CHD

Question 28

Probenecid is CI in __ and not rec in __

Answer 28

Urolithiasis: prevents tubular reabsorption of urate Not rec if CrCl < 50ml/min

Question 29

What is first line for ULT?

Answer 29

Allopurinol. Cheaper than febuxostat

Question 30

What is allopurinol dose for ULT?

Answer 30

- Initiation: ≤ 100 mg/day [start w lower doses in CKD stage ≥ 3 e.g. ≤ 50 mg/day] - Titration: in 50 to 100 mg increments every 2-8 weeks [Monitor serum urate- <6mg/dL, clinical response & drug tox- SCAR] - Usual maintenance: > 300 mg/day [ok for renal impairment too] - Max dose: 800-900 mg/day [if normal renal function] since we treat to target, can increase dose.

Question 31

What is febuxostat dose for ULT?

Answer 31

- Initiation: ≤ 40 mg/day - Titration: 80 mg/day if treatment target not met after 2-4 weeks

Question 32

When will febuxostat be considered over allopurinol?

Answer 32

When pt is intolerant to allopurinol i.e SCAR

Question 33

What is probenecid dose for ULT?

Answer 33

- Initiation: 250 mg BD x 1 week, then 500 mg BD - Titration: in 500 mg every 4 weeks as tolerated if smx not controlled - Usual maintenance: ≤ 2 g/day

Question 34

What to counsel pts on probenecid?

Answer 34

Keep hydrated (>=2L of water) to prevent kidney stones from forming --> urolithiasis

Question 35

Why should we "start low, go slow" for ULT?

Answer 35

Dont want to precipitate another gout flare

Question 36

Pts w G6PD def on probenecid has a risk of __

Answer 36

Hemolytic anemia

Question 37

When does SCAR usually occur after Tx initiation?

Answer 37

First few wks to months

Question 38

What is the allele that increases the risk of allopurinol-induced SCAR

Answer 38

HLA-B*5801

Question 39

Is routine genotyping done before starting allopurinol and why?

Answer 39

No, low positive predictive value (PPV) of 2% & the lack of alternative cost-effective ULT options.

Question 40

Allopurinol genotyping is more useful in pts with __

Answer 40

Renal impairment Older age

Question 41

What smx to counsel pts on SCAR?

Answer 41

- Flu like smx like fever, body aches, unwell - Mouth ulcers, sore throat - Red or sore eyes - Rashes Usually in first 3 months but may also happen after 3months

Question 42

What DDI w allopurinol increases bone marrow suppression?

Answer 42

6-mercaptopurine Azathioprine Cyclophosphamide

Question 43

What DDI w allopurinol increases hypersensitivity rxn?

Answer 43

- ACEi - Loop diuretics - Thiazide / Thiazide-like diuretics - Ampicillin/amoxicillin

Question 44

What should you monitor if allopurinol is taken with carbamazepine or warfarin?

Answer 44

Carba - SJS/TEN Warfarin - bleeding

Question 45

ULT-prophylaxis against acute flares treatment

Answer 45

- Colchicine 0.5 mg OD - Low-dose oral NSAID / Coxib (e.g. celecoxib 200mg OD) - Low-dose oral corticosteroid (e.g. prednisolone 5 – 7.5 mg OD) For 3 – 6 months

Question 46

Usually when will ULT Tx be stopped

Answer 46

No flares for >=1yr and no tophi

Question 47

What is non-pharm to reduce flares?

Answer 47

Limit alcohol intake Limit purine-rich foods Limit high-fructose corn syrup Weight management

Question 48

Can you initiate ULT during acute flares?

Answer 48

NO unless pt is alr on ULT, can still continue during flares

Question 49

What foods are high in purine?

Answer 49

Asparagus Cauliflower Mushroom Red meat Anchovies (ikan bilis) Durain Peanuts Organ meat eg. liver Alcohol

Question 50

Which HTN is preferred in gout?

Answer 50

ACEi (enalapril and captopril) or ARB (losartan) has uricosuric effect Dont give HCTZ