Gout

Question 1

DDx of acute monoarthritis?

Answer 1

Crystal arthropathy

• gout - urate deposition
• pseudogout (calcium pyrophosphate deposition)
• calcium oxalate crystal deposition

Septic arthritis

• gonoccocal (associated sx include tenosynovitis, a new rash, uretheral discharge)
• non gonoccocal (staph aureus, hx of IVDU, prosthetic joint, joint surgery, immunosuppression)

Osteoarthritis (typically milder sx)

Rheumatoid arthritis (rarely presents as a monoarthritis) 
Psoriatic arthritis, reactive artheritis, Enteropathic arthritis acn cause inflammatory bowel disease 

(ref Bones and Joints Check 2015)

Question 2

How do you differentiate between septic joint and gout?

Answer 2

Crystal arthropathy can present in an identical manner to gout.

Cannot reliably distinguish with clinical presetation, WCC, ESR/CRP or synovial WCC counts.

If high suspicion of septic arthritis - joint aspiration and IV

If aspirate is negative for culture - not septic joint

Looking for urate crystals

(ref Bones and Joints Check 2015)

Question 3

What causes gout?

Answer 3

Hyperurecemia -> deposition in joints -> inflammatory reaction = gout → subclinical chronic syndovitis / bone erosion and cartilage loss

(ref: NPS article 2004, mangement of acute gout, Dr Neil McGill)

Question 4

How does gout present?

Answer 4

1/ Acute onset, nocturnal pain with swelling and erythema and loss of function.

> 1st episode 60% have 1st MTP involvement
Can present in elbows, wrist, carpal and tarsal joints, ankles and knees (e.g. olecranon bursitis)
Elderly patients can present as a poly-articular disease

Question 5

Is there a difference in how it presents in men vs women?

Answer 5

Men tend to be mono articular, females tend to present poly-articular presentation.

Question 6

How do you differentiate between septic joint and gout?

Answer 6

Crystal arthropathy can present in an identical manner to gout.
>Cannot reliably distinguish with clinical presentation, WCC, ESR/CRP or synovial WCC counts.
>If high suspicion of septic arthritis - joint aspiration then IV abx.
>If aspirate is negative for culture - not septic joint
→ for gram stain, culture and synovial fluid examination, crystals

(ref: NPS article 2004, mangement of acute gout, Dr Neil McGill)

Question 7

Treatment of acute gout:

Answer 7

1/ NSAIDs or COX-2 inhibitors for the duration of the attack and for one further week after
2/ Colchicine 1mg as soon as possible, then 500micrograms one hour later (don’t repeat within three days)
3/ Oral prednisolone 15-30mg for 3-5/7
(ref: NPS article 2016, management of acute gout)

Question 8

Definition of hyperurecemia in

1/men 2/women?

Answer 8

Hyperuricaemia is defined as a serum uric acid
more than 0.42 mmol/L in men.
more than 0.36 mmol/L in women

Question 9

What is the urate target for patients?

Answer 9

Without tophi <0.36mmo/L

With toph <0.30mmol/L

Question 10

What % of patients with hyperurecemia develop gout? Is there evidence to decrease uric acid levels in asymptomatic patients?

Answer 10

10%

Nil evidence of urate lowering therapy in asymptomatic patients

Question 11

Which conditions can precipitate gout?

Answer 11

IHD, HT, CKD - independent risk factors for gout
(ref etg)

Obesity - Increase insulin in obese patients inhibits the secretion of uric acid (ref etg)

Question 12

When patient is on urate lowering therapy, prophylaxis should be used for 6 months to prevent flares of gout.

Answer 12

1/ Colchicine 
500micrograms BD (normal renal function)
500micrograms daily (renal impairment) 

OR

2/ Prednisolone 5mg daily (etg)

Question 13

What is colchicine and what’s its MOA?

Answer 13

Xanthine → hypoxanthine → uric acid
(xanthise oxidase catalyses both of these reactions)
Colchicine is a xanthine oxidase inhibitor
(ref: NPS article 2016, management of acute gout)

Question 14

What is the MOA of allopurinol?

Answer 14

Allopurinol purine analogue competitively inhibits xanthine oxidase (reduces the production of uric acid)

Question 15

How do you start allopurinol?

Answer 15

1/ In patients with normal renal function, allopurinol should be started at a dose of 100 mg daily for the first month.
2/Increase the daily dose by 50 mg every 2–4 weeks until the target serum uric acid concentration is reached.
3/Plasma urate concentrations can be measured monthly during this tit-ration phase and doses higher than 300 mg daily are often required to reach the target

Maintenance, oral, usually 300–600 mg (maximum 900 mg) daily, irrespective of renal function (Ref AMH).

(ref: NPS article 2016, management of acute gout)

Question 16

Side effects of allopurinol?

Answer 16

Nausea, vomiting
Drowsy
Rash or flaking of skin
Allopurinol hypersensitivity syndrome (SJohnsons, eosinophilia, leukocytosis, fever, hepatitis, renal failure -> mortality = 27%)

Question 17

For patients who cannot tolerate Allopurinol, what is the new xanthine oxidase inhibitor?

Answer 17

Febuxostat = new xathine oxidase inhibitor
It’s not a purine analogue
40mg daily is clinically equivalent to allopurinol 300mg daily

If the serum uric acid is greater than 0.36 mmol/L after 2–4 weeks of therapy, febuxostat 80 mg once daily is recommended.

Some cardiovascular events associated with febuxostat & it costs more than allopurinol.

Question 18

What are the contraindications for Febuxostat?

Answer 18

Febuxostat is contraindicated in patients with ischaemic heart disease or congestive heart disease and, like allopurinol, is not recommended in patients taking azathioprine or mercaptopurine
(ref: NPS article 2016, management of acute gout)

Question 19

When should urate lowering therapy be considered?

Answer 19

Gout + one of 
Tophi
2 or > attacks / year
CKD (Stage 2 or worse)
Urolithiasis 
(ref: NPS article 2016, management of acute gout)

Question 20

What are uricosuric drugs?

Answer 20

These drugs promote the renal excretion of uric acid and are effective in controlling serum urate.
E.g. Probenecid - inhibit organic anion transporters in the kidney
Caution required in those that have uric acid stones
(ref: NPS article 2016, management of acute gout)

Question 21

FBC & CK should be measured before starting colchicine in the long term, why?
What are the side effects of colchicine?

Answer 21

Common (>1%)
diarrhoea, nausea, abdominal discomfort, vomiting, pharyngolaryngeal pain

Infrequent (0.1–1%)
GI haemorrhage, rash

Rare (<0.1%)
peripheral neuropathy, myopathy, myalgia, rhabdomyolysis, alopecia, hepatitis, myelosuppression, agranulocytosis, thrombocytopenia, leucopenia, aplastic anaemia, arrhythmias, respiratory failure, hypersensitivity, angioedema