Gout is the most common form of inflammatory arthropathy and estimated to affect 1 in 40 people in the UK.1
The rising prevalence of gout is attributed to longevity, comorbidities and lifestyle factors such as obesity.2
Arthritis Research UK and the British Society for Rheumatology have highlighted the following issues that contribute to suboptimal management of gout in primary care, despite effective treatments being available:
- uncertainties about initiating urate-lowering therapies (ULTs)
- not reducing urate levels sufficiently to prevent further attacks
- failing to address patient risk factors
- patient compliance.
This update outlines the latest recommendations on acute and long-term treatment of gout.
Clinical features and pathogenesis
Gout is characterised by the acute onset of excruciating joint pain, with associated swelling, erythema and tenderness. The first metatarsophalangeal (MTP) joint is most commonly affected in the first attack (but gout can affect other joints, such as the knee, ankle and elbow).
Always consider bacterial infection (septic arthritis) in the differential diagnosis. Other causes of an acute monoarthritis include other crystal arthropathies, such as pseudogout, osteoarthritis, trauma, and rheumatoid and seronegative arthritis.
Gout can be diagnosed on the basis of good history-taking and examination, but when in doubt, the affected joint should be aspirated.
The underlying risk factor for gout is an elevated serum uric acid level, but not all patients with hyperuricaemia will develop the disease. Hence, the clinician should be wary of checking a uric acid level in a well person with no history of gout. The diagram below summarises the pathogenesis of gout which is important to appreciate, in order to understand the aim of therapeutic treatment.
Treatment of acute gout
In a patient with no contraindications, first-line treatment comprises a non-steroidal anti-inflammatory drug (NSAID), such as naproxen 750mg initially and thereafter, 250mg every eight hours until the episode has passed.
Diclofenac is effective, but the MHRA has issued warnings regarding its cardiovascular risk being similar to selective cox-2 inhibitors. Diclofenac is now contraindicated in patients with established IHD, peripheral arterial disease, cerebrovascular disease and heart failure.3
Indometacin, the historical choice for gout, is no longer recommended due to gastrointestinal (GI) and renal toxicity.4
Before prescribing NSAIDs, assess the risk of GI side-effects in the patient and consider adding a PPI. The selective cox-2 inhibitor etoricoxib 120mg daily (for a maximum of eight days) is another alternative in patients at risk of GI toxicity.
Colchicine is an alternative first line therapy where NSAIDs are contraindicated or cannot be tolerated. A low-dose regimen, 0.5mg two to four times daily, is advised. This is as effective as traditional larger doses, but results in lower rates of GI side-effects.
Before prescribing colchicine in patients on multiple medications it is important to check your prescribing formulary for potential drug interactions. For example, there is increased risk of colchicine toxicity with macrolide antibiotics, and verapamil and diltiazem.5 The BNF also advises caution when co-prescribing with a statin due to possible higher risk of myopathy.
Where neither an NSAID nor colchicine can be tolerated, a course of oral or IM corticosteroid can be given. Joint aspiration and intra-articular steroid injection are not commonly undertaken, but can bring instant relief.4
With regard to guidelines on prescribing oral steroid, CKS (Clinical Knowledge Summaries) could find no studies on optimum dose or duration of prednisolone in acute gout treatment, but state that a short course (such as 5 days) of 40mg or less is relatively safe.6
Pain and inflammation may also be relieved by local application of icepacks, staying in cool environments (for example, avoiding sitting in front of a fire), keeping hydrated (2 litres of fluid daily) and using a bed cage (a metal frame that raises the bedclothes) to keep the bedclothes from touching the affected foot.
Alongside therapies, good communication and information sharing with the patient are imperative for effective management. Ideally, patients should be given an information leaflet on gout or a reference to an online resource (see references).
A follow-up appointment should be arranged and the patient's risk factors (see box 1) assessed and treated, and a thorough medication review should be undertaken.
|Box 1: Risk factors for gout|
All newly diagnosed patients should have their weight and BP checked, as well as blood glucose, lipid profile and U&Es. Serum urate levels can drop during the acute phase of gout, so it is best to check levels four to six weeks after an acute presentation to assess the patient's baseline level and confirm the presence of hyperuricaemia.
Unless indicated for heart failure or chronic kidney disease (CKD), diuretics should be discontinued because they can precipitate gout. Aspirin has an association with gout, but low doses are thought to have an insignificant effect on serum urate levels, so it should be continued when being taken for cardiovascular prophylaxis. However, analgesic doses of aspirin should be avoided.7
The overriding aim of long-term gout management is to lower serum urate levels to below the physiological saturation threshold of urate in body tissues.
This can be achieved by preventing formation of new urate crystals and/or by the dissolution of existing crystals. Remember that non-pharmacological urate-lowering measures include weight loss and the restriction of alcohol and purine intake (see box 1).
ULTs are the mainstay of long-term pharmacological management and the indications for starting them are:
- Recurrent episodes of gout (for example, three or more in 12 months).
- Gouty tophi formation.
- Radiographic joint damage.
- Renal urate stones and urate nephropathy.
The European League Against Rheumatism stipulates a serum urate level treatment target of <360micromol/L. The British Society for Rheumatology target is <300micromol/L. Arthritis Research UK recommends a 'sensible compromise between these two recommendations' and states that 'lower levels are desirable whenever possible'.
The most widely used ULT agent is the xanthine oxidase inhibitor, allopurinol. It is highly effective, easy to administer and inexpensive. However, all too often sub-therapeutic doses are prescribed.8
The usual starting dose of allopurinol is 100mg daily (50mg if there is significant CKD). Doses should then be increased by increments of 100mg according to serum urate levels (checking them every four weeks would be a reasonable interval).
The maintenance dose is normally 300mg daily, but some patients may require more, with a maximum recommended dose of 900mg daily in divided doses (in patients with normal renal function).4 Once target levels have been reached, patients should have annual serum urate measurements and treatment is usually lifelong.
The most common adverse effect of allopurinol is the precipitation of an acute flare of gout. This is due to urate lowering resulting in urate crystals being shed from articular cartilage into the joint space, resulting in acute inflammation. The impact and risk of an allopurinol-induced gout flare can be reduced by:
- forewarning the patient and offering reassurance
- not stopping the allopurinol in the event of an acute attack
- avoiding initiating treatment during an acute attack (wait approximately two weeks until resolution of acute gout)
- starting treatment in low doses and gradually titrating
- coprescribing an NSAID (+/PPI) or low-dose colchicine (0.5mg once or twice daily) with allopurinol until the target urate level is achieved.3
Allopurinol is generally well tolerated, but it is important to be aware of adverse events such as rash, deranged liver function and bone marrow suppression. It is also associated with a very rare hypersensitivity reaction characterised by a severe rash, fever and multi-organ failure. This occurs most commonly in patients with significant renal impairment.
Important! Do not stop allopurinol in the event of an acute attack - forewarn the patient, avoid initiation during an attack, start treatment at low doses and add an NSAID or low-dose colchicine
In conclusion gout can be managed well in primary care with allopurinol, however for those patients who cannot tolerate allopurinol, the novel xanthine oxidase inhibitor febuxostat may be appropriate.
Studies have shown better achievement of target urate level and it is well tolerated.4 However, trial data on febuxostat versus allopurinol titrated up to full therapeutic doses are lacking.
NICE has approved febuxostat as a second-line option for long-term gout management where allopurinol cannot be used and clear guidance on how to prescribe it can be found at cks.nice.org.uk/gout#!scenario:1.
Co-prescribing febuxostat with an NSAID or colchicine is advised to prevent acut gout attacks.
- Dr Porter is a GP in Essex
This is an updated version of an article that was first published in January 2014.
- Kuo C-F, Grainge M, Mallen C, Zhang W et al. Ann Rheum Dis 2015; 74: 661-667
- Arthritis Research UK. Updated gout guidelines. Synovium spring 2013; issue 38.
- MHRA Diclofenac: new contraindications and warnings. June 2013.
- Arthritis Research UK. Gout: presentation and management in primary care. Hands On summer 2011; issue 9.
- Terkeltaub RA, Furst D E, DiGiacinto J L, Kook, K A et al (2011), Arthritis & Rheumatism 2011: 63: 2226–2237
- Clinical Knowledge Summaries. Gout. Scenario: acute gout. April 2015.
- Jordan KM, Cameron JS, Snaith M et al. British Society for Rheumatology and British Health Professionals in Rheumatology Guideline for the Management of Gout. Rheumatology 2007; 46 (8) 1372-1374
- Lipworth W, Kerridge I, Brett J et al. BMJ 2011; 343: d7459