Gout diagnosis and treatment

Gout is a type of inflammatory arthritis induced by the deposition of monosodium urate crystals in synovial fluid and other tissues, associated with hyperuricaemia, which is defined as a serum urate level of 6.8mg per decilitre (404μmol per litre) or more, the limit of urate solubility at physiological temperature and pH. Human bodies lack uricase and thus cannot convert urate to soluble allantoin as the end product of purine metabolism. Hyperuricaemia, which is caused by the overproduction of urate or, more commonly, by renal urate under-excretion, is necessary but not sufficient to cause gout.

Diagnosis

The diagnosis of gout requires synovial fluid or tophus aspiration to identify negatively birefringent monosodium urate crystals under polarising microscopy, but crystal evaluation is not routinely performed in clinical practice. Hyperuricaemia may not be present during acute gout attacks and therefore may not be useful for diagnosis. 

Diagnosis of acute gout is largely clinically based on a characteristic presentation with rapid (within 24 hours) development of severe pain, erythema and swelling in the first metatarsophalangeal joint, or other typical distribution. Differential diagnosis of acute gout includes calcium pyrophosphate dehydrate or other crystal-induced arthritides and a septic joint. If a septic joint is suspected, joint aspiration with Gram staining and culture must be performed.

The main aim of therapy for acute gout is rapid relief of pain and disability caused by intense inflammation. Options for managing acute attacks include the use of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, glucocorticoids and, possibly, corticotropin. 

Pharmacological treatment

First-line agents for acute attacks are NSAIDs and colchicines, and adjunctive measures include applying ice to and resting the affected joint. NSAIDs should be avoided in patients with renal or hepatic impairment, bleeding disorder, congestive heart failure or allergy, and may increase the risk of adverse thrombotic and gastrointestinal tract events. Naproxen may be used at a dose of 375-500mg orally twice daily for three days, then 250-375mg orally twice daily for four to seven days or until the attack resolves. Indomethacin may be given 50mg orally three times daily for three days, then 25mg orally three times daily for four to seven days or until the attack resolves.

In a randomised trial, 1.2mg of colchicine at the onset of a flare, followed by 0.6mg one hour later, was significantly more likely than placebo to be associated with pain reduction of 50% or more 24 hours later (rates: 37.8% versus 15.5%, respectively). Colchicine should be avoided in older adults and in patients with renal or hepatic impairment or known gastrointestinal tract symptoms.

When the use of NSAIDs or colchicine is poorly tolerated or contraindicated, glucocorticoids like prednisolone, prednisone or corticotropin may be prescribed for acute gout.

Lowering urate levels

To help prevent acute flares and development of tophi in the patient with gout, urate-lowering therapy may be helpful, but not without risk. Urate-lowering therapy should be considered in patients with hyperuricaemia who have two or more gout attacks per year or tophi, as determined either clinically or radiographically. 

Xanthine oxidase inhibitors, uricosuric agents and uricase agents are three classes of drugs approved for lowering urate levels. Allopurinol is the most commonly prescribed xanthine oxidase inhibitor, with an acceptable adverse effect profile in most patients. Approximately 2% of patients experience a mild rash, with potentially life-threatening severe hypersensitivity to allopurinol much less common. Most patients receive 300mg of allopurinol daily, but this dose may not achieve target urate levels, and daily doses up to 800mg may be used in patients with normal renal function. 

Febuxostat, another xanthine oxidase inhibitor approved by the FDA in 2009 for treatment of hyperuricaemia in patients with gout, is second-line therapy. Starting dose is 40mg orally daily, increasing to 80mg daily after two to four weeks if needed to achieve a target serum urate level. It is contraindicated for use with theophylline. No dose adjustments are needed for patients with mild-to-moderate renal or hepatic impairment. Probenecid, sulfinpyrazone, benzbromarone and other uricosuric drugs block renal tubular urate reabsorption, but they are contraindicated in patients with a history of nephrolithiasis. 

Recommendations post-diagnosis

The general recommendation for flare prophylaxis is to use colchicine at a dose of 0.6mg once or twice daily, with dose adjustments as needed for renal impairment, potential drug interactions or intolerance. Although NSAIDs are also used for prophylaxis, there are few studies that support their use.