Initial assessment and exclusion of septic arthritis
In a patient presenting with a clinical picture compatible with an acute gout flare, it is essential to exclude septic arthritis, particularly when there is abrupt onset of high fever, severe pain, erythema and swelling of a major joint, especially the knee. The affected joint is usually extremely tender on palpation, with marked restriction of both active and passive movement.
The joints most commonly involved include the knee, followed by the hip, shoulder, wrist, ankle and elbow. Although the presentation is usually monoarticular, involvement of two or more major joints, particularly in immunocompromised patients, should increase suspicion of joint infection. The presence of systemic symptoms, recent trauma, surgery, travel or risk factors for gonococcal infection further supports this possibility.
Whenever suggestive features are present or there is significant diagnostic uncertainty, the patient should be referred for urgent assessment.
Treatment of the acute flare
After septic arthritis has been excluded, treatment of the acute flare should be started as early as possible. Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the first-line options, and naproxen, indometacin or other NSAIDs appropriate to the patient’s clinical profile may be used. Gastroprotection with a proton pump inhibitor should be considered when indicated.
When NSAIDs are contraindicated or not tolerated, colchicine is an alternative first-line option. The dose should be adjusted according to renal function, with particular caution in patients with renal impairment, relevant drug interactions or other risk factors for toxicity.
Colchicine is contraindicated in severe renal impairment and when combined with certain medicines, particularly macrolides, except spiramycin. It should also be avoided during pregnancy and used with caution while breastfeeding.
Corticosteroid therapy
In patients with contraindications to both NSAIDs and colchicine, prednisolone is the main therapeutic alternative. Treatment may be continued until symptoms begin to resolve, followed by gradual dose reduction.
In more severe flares, with polyarticular involvement or involvement of several major joints, combination therapy may be required, using colchicine with an NSAID or colchicine with corticosteroid therapy. The simultaneous use of an NSAID and a systemic corticosteroid should be avoided because of the increased risk of adverse effects.
Preventive measures after the flare
Urate-lowering therapy should not be started during the acute flare. However, if the patient is already receiving urate-lowering treatment, it should be continued.
After the flare has resolved, measures should be implemented to reduce the risk of recurrence. Whenever possible, the patient’s regular medication should be reviewed, and discontinuation of medicines that contribute to hyperuricaemia should be considered, including thiazide diuretics, loop diuretics, acetylsalicylic acid in selected circumstances, ciclosporin and other medicines associated with increased serum urate levels.
Non-pharmacological measures include weight loss, regular physical activity, reduced alcohol intake, limited consumption of purine-rich foods and maintenance of adequate daily hydration.
Indications for urate-lowering therapy
Urate-lowering therapy is indicated in patients with two or more gout flares per year, gouty tophi, evidence of gout-related joint damage, recurrent uric acid nephrolithiasis or stage 2 or higher chronic kidney disease.
Once started, treatment should be continued long term and accompanied by prophylaxis against urate mobilisation flares, usually with low-dose colchicine for 6 months.
Allopurinol and febuxostat
Allopurinol is generally the first-line medicine. It should be started at a low dose and gradually titrated according to serum urate levels and renal function until the target serum urate concentration is reached.
Febuxostat may be used when allopurinol is not tolerated, is contraindicated or provides an inadequate response. It should also be titrated progressively until treatment targets are achieved.
In patients with severe renal impairment, dose adjustments should be made according to the glomerular filtration rate.
Monitoring and treatment targets
Serum urate should be monitored every 2 to 4 weeks during dose titration. The usual target is to maintain serum urate below 6 mg/dL, with a target of below 5 mg/dL recommended in patients with gouty tophi or more severe disease.
After the treatment target has been reached, it should be confirmed again after approximately 3 months, followed by monitoring every 6 months and subsequently annually, with periodic surveillance of renal function.
Precautions and referral
The occurrence of signs of allopurinol hypersensitivity, including rash, fever, liver abnormalities, persistent nausea or other systemic manifestations, requires immediate discontinuation of the medicine and contraindicates subsequent re-exposure.
Allopurinol and febuxostat should not be used concomitantly with azathioprine because of the risk of severe haematological toxicity. In these situations, as well as in cases of difficult clinical control, treatment intolerance or persistent diagnostic uncertainty, referral to Rheumatology should be considered.
