Gout can be defined as arthritis due to deposition of monosodium urate (MSU) crystals within joints causing acute inflammation and eventual tissue damage.
The duration and magnitude of hyperuricaemia is directly correlated with the likelihood of developing gouty arthritis and developing uric acid kidney stones. However, gout can occur in people with normal plasma urate levels and many people with hyperuricaemia never develop gout.
Hyperuricaemia is usually due to impaired renal excretion of urate. About 90% of people with hyperuricaemia are under-excretors of urate and about 10% are over-producers of urate. Some people are both under-excretors and over-producers of urate. In many people with hyperuricaemia, the cause is multifactorial.
The classification of gout was updated in 2015 as a result of an American College of Rheumatology/European League Against Rheumatism collaborative initiative:
- Pattern of joint/bursa involvement during symptomatic (pain and/or swelling) episode(s) ever:
- Joint(s) or bursa(e) other than ankle, midfoot or first metatarsophalangeal (MTP) joint (or their involvement only as part of a polyarticular presentation).
- Ankle or midfoot joint(s) as monoarticular or part of an oligoarticular presentation without first MTP joint involvement.
- MTP joint involvement as monoarticular or part of an oligoarticular presentation.
- Characteristics of symptomatic episode(s) ever:
- Great difficulty with walking or inability to use the affected joint(s) during a symptomatic episode ever (patient-reported).
- Can't bear touch or pressure to the affected joint during a symptomatic episode ever (patient-reported).
- Erythema overlying affected joint during a symptomatic episode ever (patient-reported or physician-observed).
- Time course of symptomatic episode(s) ever. 'Typical symptomatic episode': presence (ever) of >2 of the following, irrespective of antiinflammatory treatment:
- Time to maximal pain <24 hours.
- Resolution of symptoms in ≤14 days.
- Complete resolution (to baseline level) between symptomatic episodes.
- Clinical evidence of tophus:
- Appearance: draining or chalk-like subcutaneous nodule under transparent skin, often with overlying vascularity.
- Classic locations: joints, ears, olecranon bursae, finger pads, tendons (eg, Achilles).
- Serum urate level, off-treatment:
Categories are defined as:
- <4 mg/dL (0.24 mmoles/L).
- 4-5.9 mg/dL (0.24-0.36 mmoles/L).
- 6-7.9 mg/dL (0.36-0.48 mmoles/L).
- 8-9.9 mg/dL (0.48-0.60 mmoles/L).
- ≥10 mg/dL (≥0.60 mmoles/L)
- Ideally, the serum urate level should be scored if tested at a time when the patient was not receiving urate-lowering therapy and it was >4 weeks from the start of an episode; if practicable, retest under those conditions. If serum urate level is ≥10 mg/dl, there is no need to retest.
- Synovial fluid analysis:
- Location: symptomatic (ever) joint or bursa.
- Assessment should be performed by a trained observer.
- Imaging evidence of urate deposition:
- Double-contour sign on ultrasound, or urate deposition on dual-energy CT.
- Location: symptomatic (ever) joint or bursa.
- Appearance of gout-related erosion: cortical break with sclerotic margin and overhanging edge; excludes gull wing appearance.
- Location: radiograph of hands and/or feet; excludes distal interphalangeal joints.
- Gout is more common in men (especially in those aged 30-60 years) and in older people. Only 3-6% of people with gout have onset of the disease before 25 years of age.
- A study of UK general practice found that the prevalence of gout was 1.4%, the overall ratio of men to women was 3.6:1, and the annual incidence of gout ranged from 1.19-1.80 cases per 1,000 person-years.
- One 12-year longitudinal study of 47,150 male health professionals in the USA estimated that annual incidence of gout ranged from 1.0/1,000 for those aged 40-44 years, to 1.8/1,000 for those aged 55-64 years.
- Gout may be more common in some non-white ethnic groups. However, Asian populations and people of the Pacific Islands have a much higher prevalence and more severe disease.
Risk factors include:
- Male gender.
- Alcohol (10 or more grams per day).
- Coronary heart disease.
- Diabetes mellitus.
- Chronic kidney disease.
- High triglycerides.
- Heart failure.
One large study found that excessive consumption of purine-rich foods and alcoholic drinks are independent risk factors for gout. The study also found that fructose and sugar-sweetened soft-drinks increase the risk of developing gout whereas dairy products, coffee and vitamin C appeared to be protective against the development of gout.
- The European League Against Rheumatism (EULAR) guidelines for diagnosis suggest that the development of acute pain in a joint which becomes swollen, tender and erythematous and which reaches its crescendo over a 6- to 12-hour period is highly suggestive of crystal arthropathy, although not specifically of gout.
- 50% of all attacks and 70% of first attacks affect the first MTP.
- Other sites often affected are:
- Midtarsal joints
- Small hand joints
- The inflammation reaches its peak within 24 hours, often with fever and malaise.
Some patients may only present with connective tissue tophi.
- There is florid synovitis and swelling and extreme tenderness with overlying erythema. Untreated, the attack resolves spontaneously over 5-15 days, usually with itching and desquamation of overlying skin.
- Atypical attacks can occur with tenosynovitis, bursitis and cellulitis, with mild discomfort without swelling lasting a day or two.
- Chronic tophaceous gout - in this condition large crystal deposits produce irregular firm nodules mainly around extensor surfaces of the fingers, hands, forearms, elbows, Achilles tendons and ears.
- Typically, tophi are asymmetrical with a chalky appearance beneath the skin. Damage is usually found in the first MTP joints, midfoot, small finger joint and wrist, with restricted movement, crepitus and deformity.
- Acute attacks - sepsis and other forms of crystal-related synovitis.
- Chronic tophaceous - rheumatoid arthritis, generalised nodal osteoarthritis, xanthomatosis with arthropathy, multicentric reticulohistiocytosis.
The EULAR guidelines recommend the following evidence-based approach:
- For typical presentations such as inflammation of the first MTP joint (also known as podagra) with hyperuricaemia, a clinical diagnosis can be made with reasonable accuracy but is not definitive unless the presence of uric acid crystals can be demonstrated.
- Demonstration of MSU crystals in synovial fluid or tophi confirms the diagnosis of gout.
- Since gout can present atypically, an opportunity should be taken to examine all samples of synovial fluid aspirated from joints for MSU crystals, even if not inflamed at the time.
- Gram staining and culture of synovial fluid should be arranged, even if MSU crystals are found, since gout and sepsis can co-exist.
- Although a raised serum uric acid (SUA) level is an important risk factor for gout, the use of SUA as a diagnostic test is limited. It can be normal during acute gout, whilst patients with hyperuricaemia may never develop an attack. Studies suggest that the cut-off point above which a level can be considered raised is 360 μmol/L.
- Renal uric acid secretion (as detected by a 24-hour urine sample) may be helpful in diagnosis, particularly in patients with a family history of young-onset gout, patients whose first attack of gout was under the age of 25 years and patients with renal stones. Such patients are likely to be over-excreters of uric acid.
- X-Rays may be useful in chronic gout, when punched-out lesions, areas of sclerosis and, in the latter stages, tophi may be seen. The first lesions usually occur in and around the first MTP joint.
- Ultrasound, dual-energy CT and MRI are among the current imaging modalities that can identify urate deposition, structural joint damage, and joint inflammation in gout.
- Fasting glucose and lipids should be performed to rule out hyperglycaemia and hyperlipidaemia, as gout is commonly associated with metabolic syndrome.
An ice pack may be useful, as may rest. The joint should be elevated and trauma avoided.
Pharmacological therapeutic options include:
- Non-steroidal anti-inflammatory drugs (NSAIDs).
- Other primarily analgesic compounds.
The choice for a particular patient will depend on:
- The gap between onset of symptoms and the start of treatment.
- Risks versus benefits.
EULAR guidelines recommend colchicine and/or NSAIDs as the first-line option for acute gout.
The opportunity should be taken to discuss lifestyle issues such as weight loss, exercise, diet, alcohol consumption and fluid intake.
Canakinumab is a recombinant monoclonal antibody active as an inhibitor of proinflammatory cytokine IL-1. It is licensed for use in patients whose condition has not responded adequately to treatment with NSAIDs or colchicine, or who are intolerant of them. It can be used for the symptomatic treatment of frequent gouty arthritis attacks (at least three in the previous 12 months)[8, 9].
NSAIDs are the first-line treatment. The sooner medication is started, the more rapid the response. Consider giving the patient a stock to keep at home.
Indometacin has been traditionally used first-line in the past but there is no convincing evidence to support the use of any particular NSAID. Eight drugs are licensed for use in gout. Diclofenac, naproxen and indometacin are generally preferred.
For patients with a high risk of gastrointestinal adverse events, use a gastro-protective agent, simple analgesia, or colchicine. Tailor the dose to the needs of the patient, bearing in mind age, comorbidity and interactions with other drugs. Aim for the highest tolerable licensed dose but be aware of the Commission on Human Medicine's guidance to use NSAIDs for the shortest possible time in view of cardiovascular risk.
Colchicine is an effective treatment for gout. The British National Formulary (BNF) recommends 500 micrograms 2-4 times daily until symptoms are relieved - maximum 6 mg per course; the course is not to be repeated within three days. In practice, the maximum dose is often limited by the development of toxicity symptoms (nausea, vomiting, diarrhoea).
Colchicine is particularly appropriate when NSAIDs are poorly tolerated, in patients with heart failure and in those who are on anticoagulants[12, 13].
The drug can be effective at lower doses. Titrate up to the maximum licensed dose, according to response.
These can be given orally, intramuscularly, intravenously or intra-articularly. They are useful where NSAIDs or colchicine are contra-indicated.
There are no definitive trials regarding dosage but UK practice is to use short courses of lower doses - 15 mg/day of prednisolone or less. Randomised trials using 30-35 mg of prednisolone reported a low incidence of side-effects. Systemic steroids are widely used although a Cochrane review found limited evidence of effectiveness.
Intra-articular administration of long-acting steroids has been shown, in small trials, to be safe and effective. However, further work is needed to clarify effectiveness. It can be paired with aspiration of the joint, making it convenient to both aid diagnosis and to manage the condition. It is particularly useful for those patients with a severe monoarthritis and contra-indications to NSAIDs and colchicine. It is also useful as it is associated with minimal adverse effects and a lower risk of drug interactions. It should not be undertaken if septic arthritis is suspected.
These are useful where all other drug groups are contra-indicated or as an adjunct for pain relief. Start with paracetamol, with or without codeine, taken regularly rather than only as required.
If there is no improvement after 2-3 days:
- Review the diagnosis (differentials include septic arthritis, non-urate arthropathy, other arthritides and haemochromatosis).
- Check medicine compliance.
- Increase doses to the maximum.
- If the patient still fails to improve, consider combining treatments, or seek specialist advice.
Prophylactic treatment between attacks
- Drink alcohol sensibly (eg, keep to recommended limits and have three alcohol-free days a week). Beer or spirits should be avoided (there is a particularly strong link with beer, stout and port wines) but wine in moderation is not associated with an increased risk.
- Avoid dehydration.
- Dietary intervention - reduction of purine-based foods.
- Meat or seafood significantly increases the incidence of gout.
- Highest purine levels are found in heart, herring, sardines and mussels.
- Other foods which are very rich in purines include liver, kidneys, yeast extracts and oatmeal.
- Soya foods are also high in purines but are less likely than meat or seafood to lead to gout.
- It is the quantity of purine-rich food consumed that is more important than the absolute purine content in each food.
- Soft drinks containing high levels of fructose can affect the levels of purines and should also be avoided.
- There is no evidence to support a reduction in purine-rich vegetables such as peas, beans, mushrooms or cauliflower.
- Weight reduction - there is increasing evidence to support a link between obesity and gout.
- Regular exercise is beneficial.
- Smoking cessation should be encouraged.
Manage risk factors
These may include:
- Drugs causing hyperuricaemia:
- Thiazides and loop diuretics.
- Low-dose salicylates - eg, aspirin <1 g/day, pyrazinamide, ethambutol, nicotinic acid, ciclosporin.
- Impaired renal function.
- Hyperlipidaemia, especially hypertriglyceridaemia.
- Vascular disease.
- Myeloproliferative disease.
NB: aspirin in low doses (75-150 mg/day) has insignificant effects on the plasma urate and should be used as required for cardiovascular prophylaxis.
It is important to explain that medication is normally lifelong and regular monitoring is needed. Advise the person that allopurinol may cause acute attacks of gout just after initiating treatment and for some weeks afterwards. Explain that they should start their anti-inflammatory treatment as soon as possible and not stop their allopurinol during acute attacks.
For long-term control of gout the formation of uric acid from purines may be reduced with the xanthine-oxidase inhibitors allopurinol or febuxostat. Alternatively, uricosuric drugs may be used to increase the excretion of uric acid in the urine. The uricosuric drug sulfinpyrazone may be used to increase the excretion of uric acid in the urine. Sulfinpyrazone can be used instead of allopurinol, or in conjunction with it in cases that are resistant to treatment.
Manage recurrent attacks of gout by starting allopurinol after two or more attacks within a year.
- Uric acid-lowering drug therapy should also be offered to patients with:
- Renal insufficiency.
- Uric acid stones and gout.
- The need for continuing diuretic treatment.
- Allopurinol should never be started during an acute attack. Wait for 1-2 weeks after the attack resolves.
- Start with a low dose (50-100 mg) and increase in 50-100 mg increments every 2-4 weeks until SUA level is below 300 μmol/L.
- Maximum dose is 900 mg daily.
- The timescale for increasing in dose may need to be slower in some patients, with frequent checks of renal function, if renal function is known to be impaired.
- Co-prescribe colchicine or a low dose NSAID to prevent an attack of gout whilst initiating therapy, and continue until after hyperuricaemia has settled (usually a total of three months).
- If an acute attack develops during treatment, maintain the dose but add colchicine or NSAIDs.
- If neither NSAIDs nor colchicine are tolerated, or both are contra-indicated, consider low-dose oral prednisolone. However, it may be preferable to seek specialist advice.
Allopurinol, a xanthine oxidase inhibitor, is considered one of the most effective urate-lowering drugs and is frequently used in the treatment of chronic gout. However, a Cochrane review found moderate-quality evidence of little or no difference in achieving target serum urate when allopurinol was compared with benzbromarone. Allopurinol seemed more successful than placebo and may be less successful than febuxostat in achieving a target serum urate level based on low- to moderate-quality evidence.
This is recommended as an option for the management of chronic hyperuricaemia in gout but only in patients where urate deposition has already occurred and not in cases where urate formation has greatly increased such as malignancy. The Medicines and Healthcare products Regulatory Agency (MHRA) issued advice in 2012 that febuxostat can cause serious hypersensitivity reactions, including Stevens-Johnson syndrome and acute anaphylactic shock. The National Institute for Health and Care Excellence (NICE) has issued guidance recommending that febuxostat should be reserved for patients intolerant of allopurinol (ie adverse effects severe enough to warrant discontinuation, or to prevent full dose escalation for optimal effectiveness).
Uricosurics act by increasing renal urate excretion, mediated by selective inhibition of organic anion transporters present in the proximal renal tubular cells. All uricosurics have an increased risk of precipitation of urate stones. Sulfinpyrazone is the main uricosuric available in the UK.
- Renal disease:
- Chronic urate nephropathy results from widespread deposition of urate crystals in the interstitium of medulla and pyramids, causing inflammation and fibrosis.
- Gout patients who have a 24-hour urinary excretion of uric acid above 780 mmol/L have a 50% risk of developing urate and oxalate kidney stones. Those with a measured urate excretion greater than 800 mg per 24 hours may benefit from allopurinol prophylaxis to prevent urate nephropathy.
- Severe degenerative arthritis.
- Secondary infections.
- Recurrent painful episodes.
- Carpal tunnel syndrome (rare).
- Nerve or spinal cord impingement.
First acute attacks usually completely resolve within 3-10 days. Attacks have been reported to recur in 62% of people within a year. Recurrent acute episodes and the development of chronic gout lead to progressive joint damage, pain and disability. Serum uric acid levels greater than 360 µmol/L are associated with increased risk for recurrent gout attacks.
Further reading and references
Gout; DermNet NZ
The British Society for Rheumatology Guideline for the Management of Gout; The British Society for Rheumatology (May 2017)
Rheumatology AF, Rheumatologist PK; The management of gout. Aust Prescr. 2016 Aug39(4):119-122. Epub 2016 Aug 1.
Gout; NICE CKS, April 2015 (UK access only)
Neogi T, Jansen TL, Dalbeth N, et al; 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatol. 2015 Oct67(10):2557-68. doi: 10.1002/art.39254.
2016 updated EULAR evidence-based recommendations for the management of gout; European League Against Rheumatism (2016)
Roddy E, Choi HK; Epidemiology of gout. Rheum Dis Clin North Am. 2014 May40(2):155-75. doi: 10.1016/j.rdc.2014.01.001. Epub 2014 Feb 19.
Thissen CA, Frank J, Lucker GP; Tophi as first clinical sign of gout. Int J Dermatol. 2008 Nov47 Suppl 1:49-51. doi: 10.1111/j.1365-4632.2008.03961.x.
Vargas-Santos AB, Taylor WJ, Neogi T; Gout Classification Criteria: Update and Implications. Curr Rheumatol Rep. 2016 Jul18(7):46. doi: 10.1007/s11926-016-0594-8.
British National Formulary (BNF); NICE Evidence Services (UK access only)
Singh JA; Emerging therapies for gout. Expert Opin Emerg Drugs. 2012 Dec17(4):511-8. doi: 10.1517/14728214.2012.736488. Epub 2012 Nov 6.
Burns CM, Wortmann RL; Latest evidence on gout management: what the clinician needs to know. Ther Adv Chronic Dis. 2012 Nov3(6):271-86. doi: 10.1177/2040622312462056.
Laubscher T, Dumont Z, Regier L, et al; Taking the stress out of managing gout. Can Fam Physician. 2009 Dec55(12):1209-12.
Darling EK, McDonald H; A meta-analysis of the efficacy of ocular prophylactic agents used for the prevention of gonococcal and chlamydial ophthalmia neonatorum. J Midwifery Womens Health. 2010 Jul55(4):319-27.
Wertheimer AI, Davis MW, Lauterio TJ; A new perspective on the pharmacoeconomics of colchicine. Curr Med Res Opin. 2011 May27(5):931-7. doi: 10.1185/03007995.2011.563284. Epub 2011 Mar 3.
Richette P, Bardin T; Colchicine for the treatment of gout. Expert Opin Pharmacother. 2010 Dec11(17):2933-8. doi: 10.1517/14656566.2010.529432.
Rider TG, Jordan KM; The modern management of gout. Rheumatology (Oxford). 2010 Jan49(1):5-14. doi: 10.1093/rheumatology/kep306. Epub 2009 Oct 5.
Seth R, Kydd AS, Buchbinder R, et al; Allopurinol for chronic gout. Cochrane Database Syst Rev. 2014 Oct 14(10):CD006077. doi: 10.1002/14651858.CD006077.pub3.
Febuxostat for the management of hyperuricaemia in people with gout; NICE Technology Appraisal Guidance, December 2008
Sattui SE, Gaffo AL; Treatment of hyperuricemia in gout: current therapeutic options, latest developments and clinical implications. Ther Adv Musculoskelet Dis. 2016 Aug8(4):145-59. doi: 10.1177/1759720X16646703. Epub 2016 May 2.
Just want to share what I guess is good news, my uric acid down to 5.6, probably the lowest it's been in a long time. And I haven't had either a gout or pseudo-gout attack in going on two years.Due...jx41870
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