Gout

Question 1

WHat is the prevalence of gout in Australia

Answer 1

5.2-6.8% (M8.5 F2.1)

Question 2

Which ethnic groups have higher prevalence?

Answer 2

Maori and pacific islanders

Question 3

What is the pathiophys?

Answer 3

Hyperuricaemia > precipitaiton of monosodium urate in joints > inflammation

Question 4

What is the solubility threshold for monosodium urate?

Answer 4

0.405mmol/L

Question 5

What is urate a end-product of?

Answer 5

Purine catabolism

Question 6

Which is the precursors and what converts it into urate?

Answer 6

Xanthine, xanthine oxidase

Question 7

What are the mechanisms effecting urate levels?

Answer 7

Intrinsic production
Extrinsic intake
Excretion

Question 8

How is urate excreted

Answer 8

Renal and GIT

Question 9

What proportion of urate overproduction is intrinsic?

Answer 9

10%

Question 10

What are the 3 inborn errors of metabolism leading to primary urate over-production?

Answer 10

Accelerated purine synthesis - PRPP synthase enzyme hyperactivity
Impaired purine salvage - HGPRT1 deficiency
Hereditary defect of energy metabolism

Question 11

Which syndrome has complete HGPRT1 deficiency? Which has partial?

Answer 11

Complete - Lesch-Nyhan syndrome

Partial - Kelley-Seegmillar syndrome

Question 12

What conditions lead to 2nd over production of urate?

Answer 12

Autoimmune and haemolytic aneamia
TLS
Myeloproliferative disorders

Question 13

What foods are high in purine

Answer 13

Seafood
Red meat - organ meat
Fructose containing
Alcohol

Question 14

How does alcohol increase urate

Answer 14

Liver damage - increased purine turner
Increased lactate reduces renal excretion
Beer - high in purine

Question 15

What is the urate transporter in the GIT?

Answer 15

ABCG2

Question 16

WHere is urate reabsorpted?

Answer 16

Prox tubule 90-98%

Question 17

What are the renal transporters of urate?

Answer 17

URAT1; OAT4
Glut9a
OAT1
ABCG
MRP4, NPT1, NPT4

Question 18

How does CKD lead to high urate?

Answer 18

Decreased filtered urate load

Question 19

Which medications lead to under secretion?

Answer 19

Diuretics
Low dose aspirin
Pyrazinamide
Ciclosporin

Question 20

Which receptors recognise MSU crystals?

Answer 20

TLR 2 and 4

Question 21

Which cytokine is produced?

Answer 21

IL-1

Question 22

What mechanisms self-limit gout flares?

Answer 22

Coating of cystals with synovial fluid proteins - inhibit phagocytosis
Release of local anti-inflam molecules eg ACTH
NETs

Question 23

How does gout present?

Answer 23

Acute gout flare
Subcut tophi
Chronic gouty arthritis

Question 24

Which joints are affected?

Answer 24

Any. Most commonly 1st MTP

Question 25

How long does pain take to occur with an acute flare?

Answer 25

4-12 hours

Question 26

How long does an acute flare take to resolve?

Answer 26

1-2 weeks

Question 27

What are tophi?

Answer 27

Network of MSU crystals plus host response factors

Question 28

What are the DDx of gout?

Answer 28

``` CPPD Septic arthritis Trauma Spondyloarthritis Sarcoidosis ```

Question 29

How do MSU appear on polarized light microscopy?

Answer 29

Intra-cellular needle shaped, negatively birefringent crystal

Question 30

What are the characteristic gouty x-ray erosions?

Answer 30

Overhanging edge with sclerotic margin

Question 31

What are the US signs of gout?

Answer 31

Double contour sign Hyperechoic aggregates Tophi

Question 32

Options for acute gout flare management?

Answer 32

NSAIDs, COX-2 inhibitors Prednisolone - high doses often required Colchicine 1mg immediately, the 0.5microg one hour later (renally adjusted) Intra-articular corticosteroid injection

Question 33

What are the urate lower therapy options?

Answer 33

Xanthine oxidase inhibitors - Allopurinol, febuxostat Uricosuric agent (promote urinary excretion) - Probenicid

Question 34

How do you dose allopurinol?

Answer 34

100mg daily at commencement (50mg if eGFR <60) increased by 50-100 every 2-4 weeks until target reached Max 800-900mg daily

Question 35

What is the urate target?

Answer 35

<0.36mmol/L in all patient | <0.30 in severe gout - frequent flare, tophi, erosions

Question 36

How does allopurinol hypersensitivity snydrome present (AHS)?

Answer 36

Desquamating rash, fever, eosinophilia, end-organ damage

Question 37

How do you prevent AHS?

Answer 37

Renally adjust initial dose

Question 38

Why does ULT increased risk of flare?

Answer 38

Mobilise MSU crystals

Question 39

When to use fexuxostat?

Answer 39

If allopurinol contraindicated or not tolerated?

Question 40

What did the CARES trial show?

Answer 40

All-cause mortality and CV mortality higher with febuxostat compared to allopurinol

Question 41

What is the mechanism of uricosuric therapy?

Answer 41

Inhibit URAT1 and GLUT9 (urate resorption transporters) in the prox tubule

Question 42

What is the uricosuric therapy available in Australia and when don't you use it?

Answer 42

Probenecid | Hx of nephrolithiasis and severe CKD

Question 43

What can you use for prophylaxis which on ULT?

Answer 43

Low dose colchicine 500microg daily Low dose NSAID (eg naproxen 250mg BD) Low dose prednisoloen

Question 44

How long do you continue prophylaxis

Answer 44

6 months from initiation of ULT

Question 45

When don't you use/reduce dose colchicine?

Answer 45

CKD | Statin therapy