Gout

See also our records on Management of Acute Gout and Gout Prophylaxis.

• Asymptomatic
• Hyperuricaemia
• Acute gout
• Intercritical gout and chronic tophaceous gout

The condition can be classified into primary or secondary gout depending on the cause of hyperuricaemia:

• Primary gout occurs mainly in men age 30-60 years presenting with acute attacks.
• Secondary gout normally is due to chronic diuretic therapy. It occurs in older subjects, both men and women, and is often associated with osteoarthritis.

It affects both upper and lower limbs with acute attacks. Less often it presents with painful, tophaceous deposits (± discharge) in Heberden's and Bouchard's nodes.

• Most patients with hyperuricaemia never develop gout and gouty patients may not have hyperuricaemia at presentation.
• Patients can be over-excreters of uric acid, normo-excreters or under-excreters.
• Most cases of primary gout are due to undersecretion.¹
• Less than 10% are due to overproduction.²

• One study of epidemiology in UK general practice between the years 1990-1999 found an incidence of 11.9 -18.0 cases per 10 000 patient-years.³
• The study also found a prevalence of 1.4% in 1999.
• The male to female ratio is 9:1.⁴

Risk factors

The European League Against Rheumatism (EULAR) produced evidence-based guidelines in 2006.¹ They identified the following risk factors:

• Male sex
• Meat
• Seafood
• Alcohol (10 or more grams per day)
• Diuretics
• Obesity
• Hypertension
• Coronary heart disease
• Diabetes mellitus
• Chronic renal failure
• High triglycerides

• The 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 6-12 hour period is highly suggestive of crystal arthropathy, though not specifically of gout.¹
• 50% of all attacks and 70% of first attacks affect the first metatarsophalangeal joint.
• Other sites often affected are:
  • Knee
  • Midtarsal joints
  • Wrists
  • Ankles
  • Small hand joints
  • Elbows
• The inflammation reaches its peak within 24 hours, often with fever and malaise.

Signs

• 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, cellulitis with mild discomfort without swelling lasting day or two.
• Chronic tophaceous gout - in this condition large crystal deposits produce irregular firm nodules mainly around extensor surfaces of fingers, hands, forearms, elbows, achilles tendons and ear.
• Typically, tophi are asymmetrical with a chalky appearance beneath skin. Damage is usually found in the 1st metatarsophalangeal joints, mid foot, 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 metatarsophalangeal 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 monosodium urate (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 level is an important risk factor for gout, the use of serum uric acid 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 360μmol/l.¹
• 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, and patients with renal stones. Such patients are likely to be over-excreters of uric acid.
• Radiographs 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 metatarsophalangeal joint. CT scanning may be helpful in less accessible areas.² Radiography is less helpful in early gout or during an acute attack.¹
• Fasting glucose and lipids should be performed to rule out hyperglycaemia and hyperlipidaemia as gout is commonly associated with metabolic syndrome.

The objectives in an acute attack are to relieve pain and inflammation as quickly as possible:

• An ice pack may be useful, as may rest.^5,6
• Drug options include non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, corticosteroids and analgesics.⁷
• The choice for a particular patient will depend on contra-indications, the gap between onset of symptoms and the start of treatment, and risks versus benefits.

NSAIDs

• NSAID are the first-line treatment. Starting medication within 24 hours produces rapid relief.⁸ Consider giving the patient a stock to keep at home.
• There are no convincing trials supporting the use of a particular NSAID.⁹ Eight drugs are licensed for use in gout. Diclofenac, naproxen and indometacin are generally preferred.⁷
• For patients with a high risk of gastro-intestinal adverse events, use a gastro-protective agent, simple analgesia, or colchicine.¹⁰
• Tailor the dose to the needs of the patient bearing in mind age,co-morbidity and interactions with other drugs.¹¹ Aim for the highest tolerable licensed dose but be aware of recent CSM guidance to use NSAID for the shortest possible time in view of cardiovascular risk.¹²

Colchicine

• There is limited evidence that colchicine is as effective as NSAID. Indometacin works quicker, but after 48 hours the effect is the same.⁹
• Colchicine can be used as an alternative when NSAID are poorly tolerated, in patients with heart failure and in those who are on anticoagulants.¹³
• Higher doses cause diarrhoea, but the drug can be effective at lower doses.¹⁴ Titrate up to maximum licensed dose, according to response.

Oral corticosteroids

• These are useful where NSAID or colchicine contra-indicated.
• There are no definitive trials regarding dosage, but UK practice is to use short courses of lower doses - 15 mg/day or less.^12,15
• Intra-articular injection may be used in mono-articular gout.¹⁵
• Intramuscular cortico-steroid injection can be useful in podagra.¹²

Analgesics

These are useful where all other drug groups contra-indicated or as an adjunct for pain-relief.

• Start with paracetamol, taken regularly rather than 'prn'.
• If further analgesia is required, add codeine as a separate drug rather than in combination, so individual drugs can be titrated.^12,16

• Renal disease
  • Renal colic is seen in 10-25% patients and uric acid stones represent 5-10% all kidney stones in UK.¹⁷
  • Chronic urate nephropathy results from widespread deposition of urate crystals in the interstitium of medulla and pyramids causing inflammation and fibrosis. End stage renal failure occurs in up to 25% of cases of untreated chronic tophaceous gout.¹²
  • Gout patients who have a 24-hour urinary excretion of uric acid above 1100 mg 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

Further attacks will usually occur within the first year, if at all.¹⁸

• Prognosis is usually good with early treatment.
• Sometimes the attacks become more frequent and involve more sites eventually causing joint damage and chronic pain (usually after 10 years).

See also separate record on gout prophylaxis.

Lifestyle modification

• There is a good evidence base that reducing alcohol intake to moderate levels is helpful.¹⁹
• Dietary intervention - reduction of purine-based foods.
  • A large longitudinal study found that increased intake of meat or seafood significantly increased the incidence of gout.
  • Highest purine levels found in heart, herring, sardines, mussels.¹²
  • There is no evidence to support a reduction in purine-rich vegetables such as peas, beans, mushrooms or cauliflower, unless intake is extreme.²⁰
• Weight reduction - no controlled trials available²¹ but there is some evidence to suggest a link between obesity and high uric acid levels.²²

Manage risk factors

These include:

• Drugs causing hyperuricaemia - commonest seen in practice are thiazides and loop diuretics, but think also of low dose salicylates (e.g. aspirin < 1g/day), pyrazinamide, ethambutol, nicotinic acid, ciclosporin.²³
• Hypertension²²
• Impaired renal function¹²
• Myeloproliferative disease²⁴
• Hyperlipidaemia, especially hypertriglyceridaemia²⁵
• Vascular disease¹²

Prophylactic drugs

Regular medication to lower urate levels are indicated in patients who have frequent attacks of gout, tophi, or gouty arthritis.

• These drugs should never be started during an acute attack - wait for 2-3 weeks after the attack resolves.
• Co-prescribe colchicine or an 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 dose but add colchicine or NSAID.²⁶

Allopurinol

• Traditionally the first choice for long-term control of gout.^26,27
• Not indicated for asymptomatic hyperuricaemia.²⁶
• Useful where renal function impaired or renal stones present.^12,26

Sulfinpyrazone²⁸

• Can be used as alternative to allopurinol or as adjunct in resistant cases.
• Can be difficult to obtain, and contraindicated in renal failure.

Colchicine

• Although not a urate-lowering drug per se, colchicine is sometimes prescribed at low dose in early gout, to 'buy time' in patients undergoing lifestyle modification, before a commitment to urate-lowering drugs is made.
• Low dose corticosteroids and NSAIDs have also been used in this manner.¹²