Gout Flashcards
WHat is the prevalence of gout in Australia
5.2-6.8% (M8.5 F2.1)
Which ethnic groups have higher prevalence?
Maori and pacific islanders
What is the pathiophys?
Hyperuricaemia > precipitaiton of monosodium urate in joints > inflammation
What is the solubility threshold for monosodium urate?
0.405mmol/L
What is urate a end-product of?
Purine catabolism
Which is the precursors and what converts it into urate?
Xanthine, xanthine oxidase
What are the mechanisms effecting urate levels?
Intrinsic production
Extrinsic intake
Excretion
How is urate excreted
Renal and GIT
What proportion of urate overproduction is intrinsic?
10%
What are the 3 inborn errors of metabolism leading to primary urate over-production?
Accelerated purine synthesis - PRPP synthase enzyme hyperactivity
Impaired purine salvage - HGPRT1 deficiency
Hereditary defect of energy metabolism
Which syndrome has complete HGPRT1 deficiency? Which has partial?
Complete - Lesch-Nyhan syndrome
Partial - Kelley-Seegmillar syndrome
What conditions lead to 2nd over production of urate?
Autoimmune and haemolytic aneamia
TLS
Myeloproliferative disorders
What foods are high in purine
Seafood
Red meat - organ meat
Fructose containing
Alcohol
How does alcohol increase urate
Liver damage - increased purine turner
Increased lactate reduces renal excretion
Beer - high in purine
What is the urate transporter in the GIT?
ABCG2
WHere is urate reabsorpted?
Prox tubule 90-98%
What are the renal transporters of urate?
URAT1; OAT4 Glut9a OAT1 ABCG MRP4, NPT1, NPT4
How does CKD lead to high urate?
Decreased filtered urate load
Which medications lead to under secretion?
Diuretics
Low dose aspirin
Pyrazinamide
Ciclosporin
Which receptors recognise MSU crystals?
TLR 2 and 4
Which cytokine is produced?
IL-1
What mechanisms self-limit gout flares?
Coating of cystals with synovial fluid proteins - inhibit phagocytosis
Release of local anti-inflam molecules eg ACTH
NETs
How does gout present?
Acute gout flare
Subcut tophi
Chronic gouty arthritis
Which joints are affected?
Any. Most commonly 1st MTP
How long does pain take to occur with an acute flare?
4-12 hours
How long does an acute flare take to resolve?
1-2 weeks
What are tophi?
Network of MSU crystals plus host response factors
What are the DDx of gout?
CPPD Septic arthritis Trauma Spondyloarthritis Sarcoidosis
How do MSU appear on polarized light microscopy?
Intra-cellular needle shaped, negatively birefringent crystal
What are the characteristic gouty x-ray erosions?
Overhanging edge with sclerotic margin
What are the US signs of gout?
Double contour sign
Hyperechoic aggregates
Tophi
Options for acute gout flare management?
NSAIDs, COX-2 inhibitors
Prednisolone - high doses often required
Colchicine 1mg immediately, the 0.5microg one hour later (renally adjusted)
Intra-articular corticosteroid injection
What are the urate lower therapy options?
Xanthine oxidase inhibitors
- Allopurinol, febuxostat
Uricosuric agent (promote urinary excretion)
- Probenicid
How do you dose allopurinol?
100mg daily at commencement (50mg if eGFR <60)
increased by 50-100 every 2-4 weeks until target reached
Max 800-900mg daily
What is the urate target?
<0.36mmol/L in all patient
<0.30 in severe gout - frequent flare, tophi, erosions
How does allopurinol hypersensitivity snydrome present (AHS)?
Desquamating rash, fever, eosinophilia, end-organ damage
How do you prevent AHS?
Renally adjust initial dose
Why does ULT increased risk of flare?
Mobilise MSU crystals
When to use fexuxostat?
If allopurinol contraindicated or not tolerated?
What did the CARES trial show?
All-cause mortality and CV mortality higher with febuxostat compared to allopurinol
What is the mechanism of uricosuric therapy?
Inhibit URAT1 and GLUT9 (urate resorption transporters) in the prox tubule
What is the uricosuric therapy available in Australia and when don’t you use it?
Probenecid
Hx of nephrolithiasis and severe CKD
What can you use for prophylaxis which on ULT?
Low dose colchicine 500microg daily
Low dose NSAID (eg naproxen 250mg BD)
Low dose prednisoloen
How long do you continue prophylaxis
6 months from initiation of ULT
When don’t you use/reduce dose colchicine?
CKD
Statin therapy
