Gout Flashcards
How is urate excreted?
1/3 by the GIT
- ABCG2 transporter
2/3 filtered by the glomerulus
- 99% reabsorbed PCT - URAT1 (inhibited by probenecid, losartan, fenofibrate) and OAT4
- Tubular secretion - ABCG2 transporter
- 5-10% of the filtered load gets excreted in the end
What impairs renal clearance of urate?
Genetic
- Maori, Polynesian
Renal disease
- Especially tubular dysfunction - polycystic kidney disease, cystinuria, analgesic nephropathy, lead
ETOH
Drugs
- Thiazide, calcineurin inhibitor
Obesity
HTN
Low urine volume
Pathophysiology gout
Most hyperuricaemia is due to underexcretion of urate (rather than overproduction)
Acute
Hyperuricaemia –> monosulphate urate crystals –> phagocytosis by macrophages –> inflammasome assembly –> production of IL1B –> drive downstream inflammatory effects
Chronic
Tophi formation
Macrophage/osteoclast activation in bone lesions
Diagnosis of gout
Joint aspirate
- Strongly negative birefringent needle-shaped crystals
- Crystals are almost always there in acute gout
Betamethasone crystals (Celestone chronodose steroid injection) can look like urate crystals!!
Does a single high serum urate tell us anything about gout?
No
Actually falls during acute gout flare
However if you have multiple serum urates going back that are low, then its unlikely this person has gout
Is USS useful for diagnosis of gout?
No
Needs expertise!
BUT for exam, know the double contour sign (layer of crystals over cartilage) - very good specificity
Is Dual energy CT useful for diagnosis of gout?
Requires expertise but not as much as USS
Can be a useful test in people with recurrent attacks that can’t be aspirated e.g. midfoot
Poor sensitivity in early gout
Negative result never rules out gout
Beware of positive result in unusual sites e.g. trunk, spine
Management of acute gout
Prompt therapy is better
Choice of therapy depends on comorbidities. They all work.
NSAID
Intra-articular or systemic corticosteroid
Tetracosactrin (depot synthetic ACTH)
Colchicine
Colchicine regime for acute gout in normal renal function
1mg (x2 tablets) then 0.5mg (1 tablet) 1 hour later
- Dose adjust in renal impairment or on statin, diltiazem (CYP3A4 inhibitor)
If they still have the flare the next day, 0.5mg BD (if renal function normal) = prophylaxis
Colchicine toxicity
N&V
Diarrhoea
Acute myopathy (especially in renal failure or on CYP3A4 inhibitor e.g. statin, diltiazem, cyclosporin, clarithromycin, ketoconazole, verapamil)
- Very high CK
- Dangerous
Biologics in gout
Small role
Anakinra (IL1 inhibitor)
- Works well
- Daily injection
- In acute gout
- When they can’t have any of the other therapies e.g. renal impairment, acute wound
- $$$$, not PBS
Management of chronic gout
- Lose weight
- Stop excess ETOH
- Stop culprit drugs
- Is there another indication for losartan, fenofibrate, SGLT2i?
Urate lowering therapy
- Never urgent but can be started during a flare
- Start low, increase steadily (monthly) to reduce risk of flares
- Flare prophylaxis first 6 months (colchicine)
Who should get urate lowering therapy?
Essentially everyone with confirmed gout i.e. joint crystals
But especially if
- Frequent flares
- Tophi
- Gouty xray change
- Renal stones
- Serum urate >0.54mmol/L
- Renal impairment
Serum urate target
Low urate load <0.36mmol/L
High urate load <0.30mmol/L
- Tophi
- Erosions
- Chronic persistent symptoms
- Multiple joint involvement
The lower the urate level, the faster the crystals dissolve (takes years) so if there’s lots of prominent gouty tophi, can aim even lower.
Do dietary modifications reduce gout flares?
No
Losing weight and reducing ETOH is good for general health but won’t reduce gout flares.
Types of urate lowering therapy
1) Xanthine oxidase inhibitors
E.g. allopurinol, febuxostat (more $$, CV safety issue)
2) Uricosuric drugs
E.g. Probenacid (need eGFR >40, BD dosing), benbromarone (needs SAS approval)
E.g. Losartan, fenofibrate, SGLT2i
3) Uricase
- Rasburicase ($$$, problem with allergic reaction), pegloticase
Allopurinol
1) Dose
2) AE
3) Potential drug interactions
1) Starting dose (mg) = 100mg (if eGFR <60, then 50mg)
Increase dose every 2-4 weeks until you reach target
No dose limit even if poor renal function
2)
2% cutaneous allergy
1/1000 severe hypersensitivity (usually first 6-12 weeks, very rare after that) especially in renal impairment, thiazide (decrease excretion), initial higher doses, HLAB5801 (Han chinese, Thai, Korean, African American)
3)
Don’t combine with drugs that are metabolised by xanthine oxidase - azathioprine, 6-MP, theophylline
Thiazide diuretic decrease excretion of allopurinol –> risk of hypersensitivity
Which drug is used in allopurinol allergic/interolant patient?
Febuxostat
Febuxostat
1) AE
2) Renal impairment
1) Increased CV mortality and all cause mortality in CARES study
Since then no difference in risk of CV events
But given this risk and cost, would choose allopurinol before this.
2) No dose adjustment in moderate renal impairment
Probenecid
1) MOA
2) Precautions
3) When to use it?
1) Inhibits URATi (reabsorption of urate). Increases renal urate clearance.
2) Requires eGFR >40, needs good hydration, urinary alkalinisation
CI in history of kidney stones
3) Useful addition to allopurinol or febuxostat if not meeting target
Calcium pyrophosphate dihydrate crystal deposition
Are they always pathogenic?
No
Old people almost always have them
Presentation in CPPD
Asymptomatic, non-inflammatory OA (incidental pick up on imaging in elderly)
Acute CPP arthritis i.e. pseudogout
Chronic inflammatory CPP arthritis
Destructive arthritis
Diagnosis CPPD
Xray - chondrocalcinosis in wrist, knee, pubic symphysis (must be correlated with symptoms!)
USS - higher sensitivity than xray. Double contour sign (can be confused with gout).
CT spine for axial involvement
Synovial fluid - weakly positive birefringence, rod or rhomboidal crystals
Treatment CPPD
Acute = same as gout
Chronic inflammatory/synovitis, recurrent
- Colchicine
- Limited evidence for MTX, HCQ
- Anakinra (IL1b inhibitor) - most impressive data, consider in severe CPPD, not PBS
None proven in RCT
Hydroxyapatite - what are they?
Crystals that make up teeth and bone
Can cause calcific tendonitis, bursitis, periarthritis when these crystals burst or when there is bone damage
Steroid injection very effective
Hyperuricaemia is an independent risk factor for CV events
True or false
True
However ULT has not been shown to reduce CV events
Are uric acid crystals the same as urate crystals?
No
Urate crystals forms in joints in gout
Uric acid crystals form in acidic environments
Does hyperuricaemia or MSU crystals always cause gout?
No
Prevalence of hyperuricaemia is 20%, while prevalence of gout is 4%. But you won’t have gout unless you have hyperuricaemia.
Asymptomatic hyperuricaemia people can have evidence of MSU crystals deposition on imaging but not have gout as they don’t develop an inflammatory response to them.
What comorbidities is gout typically associated with?
CKD (under excretion of uric acid)
Hypertension
Diabetes
Obesity
CPDD is associated with which comorbidities?
HypoMg2+ Hypophos Hyperparathyroidism Haemachromatosis OA/joint injury
Does radiographic chondrocalcinosis mean pseudogout?
No
Quite common in the elderly and often asymptomatic
