B-QuiCK: Gout

B-QuiCK: Gout

Diagnosis

• Gout can be diagnosed based on:
• Clinical presentation, e.g. joint involvement with characteristic pain/swelling/erythema, presence of tophi or systemic symptoms
• History, e.g. onset, previous potential flares or elevated serum urate
• Elevated serum urate levels
• Levels during a flare are within the normal range in up to 40% of cases. If levels are normal, repeat testing once the flare has subsided
• Hyperuricaemia in an asymptomatic person is not diagnostic of gout, but may inform lifestyle changes and subsequent monitoring
• Differential diagnoses to consider include septic arthritis and calcium pyrophosphate deposition (CPPD) disease (formerly known as pseudogout)
• In addition to serum urate, request CRP to detect inflammation and assist in interpreting the validity of the urate level and a renal function test to allow for prompt urate-lowering treatment initiation, if gout is confirmed.
• Assess for relevant co-morbidities as this may influence medicine selection and the approach to long-term management

An overview of gout management in primary care.

Acute management of gout flares

• NSAIDs, corticosteroids or colchicine are equally effective at treating gout flares, so choice is based on individual factors
• Encourage rest and elevation of the affected joint (an ice pack may provide relief), and adequate hydration
• Discuss urate-lowering treatment with all patients at their first presentation (even if it is not prescribed)

Community pharmacists: be alert for persistent over-the-counter NSAID use. Refer patients to their primary care clinician for a discussion regarding urate-lowering treatments.

Treatment options for an acute gout flare:

Medicine	Dose	Notes
NSAIDs – Naproxen preferred	750 mg initially, followed by 500 mg eight hours later, then 250 mg every eight hours until the flare has settled	Avoid if eGFR < 30 mL/min/1.73 m2 Consider adding a proton pump inhibitor Consider celecoxib if intolerant to naproxen (unapproved indication)
Prednisone	20 – 40 mg, once daily, for five days or until the flare has settled	Tapering the dose over 10 – 14 days can reduce the likelihood of a rebound flare, but is not always necessary with a short course
Colchicine	Low-dose regimen*: 1 mg immediately, followed by 500 micrograms after one hour; maximum dose 1.5 mg per course If eGFR 10 – 50 mL/min/1.73 m2, reduce the initial dose by half (i.e. 500 micrograms); do not exceed 1.5 mg over three days	Do not repeat acute course within three days Do not commence prophylaxis (very-low-dose colchicine) until 12 hours or more after the acute dose is taken Ideally avoid, or use with caution, in frail patients, those who weigh < 50 kg, or patients with hepatic or renal impairment (eGFR 10 – 50 mL/min/1.73 m2) Contraindicated in patients with an eGFR < 10 mL/min/1.73 m2
Corticosteroid (triamcinolone acetonide)	Intra-articular injection, 2.5 – 40 mg	May be considered in patients where the oral route is problematic and if only one or two joints are affected Dose determined by the size of the affected joint

* This regimen is based on a trial in which patients received treatment within 12 hours of onset of the flare; efficacy may therefore be reduced if started later

Long-term management with urate-lowering treatment

Start urate-lowering treatment in patients with symptomatic hyperuricaemia and any of the following:

• Two or more flares per year (including if self-managed)
• Tophi or erosions/damage on X-ray
• Renal impairment (eGFR < 60 mL/min/1.73 m²)
• History of kidney stones (nephrolithiasis)
• Early-onset gout, e.g. aged < 40 years (higher risk in Māori and Pacific peoples)
• Very high serum urate levels, e.g. ≥ 0.6 mmol/L

Test serum urate levels:

• Prior to dose adjustment while up-titrating urate-lowering treatment, e.g. initially every four weeks
• Every 6 – 12 months for monitoring once targets have been achieved
• Avoid testing serum urate levels during a flare

Recommended target:

• < 0.36 mmol/L – for most patients; or
• < 0.30 mmol/L – for patients with severe gout, e.g. those with tophi, chronic gouty arthritis or frequent flares

Prescribe flare prophylaxis for the first 3 – 6 months of urate-lowering treatment (doses are lower than acute treatment; Click for Table)

• Can be stopped at three-month review if symptom-free and there is a substantial drop in serum urate levels
• May be required for longer than six months if frequent ongoing flares or tophi; weigh the risks (i.e. adverse effects of NSAIDs or colchicine) against the potential benefits

Allopurinol (fully funded) - first line

• Start at a low dose (renal function dependent) and slowly up-titrate until target serum urate level is reached (click for Table)
• Dose reductions are not routinely required in patients with declining renal function already established on allopurinol
• Discuss possible adverse effects, most commonly gastrointestinal symptoms, and very rarely, hypersensitivity reactions (see NZF)
• Consider checking patients of Han Chinese, Korean or Thai ancestry for the HLA-B*5801 allele before prescribing allopurinol

Before modifying the medicines regimen, assess adherence to treatment if the patient cannot meet the serum urate target

Probenecid (fully funded)

• Add if serum urate target not achieved with relatively high dose of allopurinol, e.g. 600 mg, daily
• Or monotherapy if intolerance or resistance to allopurinol
• Titrate dose according to serum urate level
• Initially, 250 mg, twice daily, for one week, then 500 mg, twice daily, increased by 500 mg every four weeks, to 1 g, twice daily (i.e. 2 g total per day), if required
• Efficacy reduces with declining renal function; avoid if eGFR < 30 mL/min/1.73 m² or nephrolithiasis
• Advise patients to drink adequate fluids (e.g. ≥2 L per day) to prevent uric acid stones and to take the medicine with, or just after, a meal
• For adverse effects, see NZF

Febuxostat (Special Authority required)

• Alternative if allopurinol and/or probenecid are ineffective or not tolerated
• Can be prescribed in combination with probenecid if target serum urate level is not achieved with febuxostat alone
• Results in a more rapid decline in serum urate which can trigger flares
• Prescribe prophylactic NSAIDs or colchicine for at least the first six months of combination treatment
• Arrange baseline liver function testing; repeat periodically thereafter based on clinical judgement
• Recommended dose is 80 mg, once daily, increased to 120 mg, once daily, after two to four weeks if the serum urate is > 0.36 mmol/L
• Maximum daily dose 80 mg if mild hepatic impairment (no dose information available for moderate to severe impairment)
• Use with caution in patients with renal dysfunction or a history of CVD (particularly heart failure and coronary artery disease)
• For adverse effects, see NZF

Supporting patients in the long term

• Acknowledge challenges and discuss concerns or barriers to regularly taking medicines; suggest strategies to make it easier, e.g. blister packaging, reminders on their phone
• Explain the importance of continuing urate-lowering treatment; urate levels return to previous levels within one week of stopping a urate-lowering medicine
• Reiterate that although biological factors (e.g. CKD, genetics) are the main causes of gout, other modifiable factors such as diet can still trigger flares. Discussion points include:
• Eat regular meals – periods of fasting/starvation may trigger flares
• Avoid/limit foods if they trigger flares, e.g. red meat, seafood (kaimoana); some purine-rich foods may be more likely to trigger flares
• Increase vegetable intake and switch to low-fat dairy products
• Limit alcohol and high fructose/sucrose drinks
• Keep hydrated
• Be aware that continuous, vigorous exercise can trigger flares
• Vitamin C supplementation is unnecessary (no evidence it reduces serum urate)

Prescribing cardiovascular medicines to people with gout

• Losartan is the preferred choice for patients with gout and hypertension
• If possible, avoid diuretics, especially high-dose thiazides (increases risk of DRESS)
• If indicated, the benefits of low-dose aspirin outweigh the risks