After the very first gout attack, provision of dietary instructions, survey of any cardiovascular disease or risk factors for such disease, as well as their treatment, as necessary, are indicated.
The treatment of intermittent or chronic gout aims to remove monosodium urate deposits from the body to make the patient completely asymptomatic.
Plasma urate levels should be lowered to below 360 µmol/l or, in a severe disease, to below 300 µmol/l to speed up the dissolving of accumulated gouty masses.
The treatment of intermittent and chronic gout is insufficient. Providing patients with comprehensive information on the clinical picture of gout, the importance of lifestyle changes and the aims of medication, as well as regular follow-up, improve the results of treatment.
Causes and prevalence
The prevalence of gout in western countries is 1.5-2.5%. Most patients are male (80-90%).
In men over 65 and women over 85, the prevalence of gout is 7% and 3%, respectively.
Gout is preceded by hyperuricaemia for several years. About 20% of the population have serum urate levels exceeding the reference range.
The main reasons for hyperuricaemia and gout becoming more common are the increasing prevalence of the metabolic syndrome Metabolic Syndrome and renal insufficiency Treatment of Chronic Renal Failure, the increasing average age of the population and increased use of alcohol, diuretics and low-dose aspirin.
Gout rarely occurs in premenopausal women or men below 25.
In pseudogout, calcium (calcium pyrophosphate) accumulates in articular cartilage and menisci and other structures around the joints as a result of local metabolism, and may be released into the joint, causing acute inflammation.
Pseudogout occurs particularly in people over 65 with arthrosis of large joints.
There may also be hereditary forms of gout and pseudogout.
Symptoms, findings and diagnosis
Acute intermittent gout
The typical symptom is sudden nocturnal onset of redness, heat, pain and swelling of the first metatarsophalangeal joint of the big toe (picture F1). Other joints that are most commonly affected are other foot joints, the ankle and the knee.
An attack may be triggered by exposure to cold, mechanical stress or injury, surgery, alcohol, starting to take antihyperuricaemic medication, diuretics or aspirin, or a meal high in purines.
The joint may be sensitive to even the lightest touch, and it is difficult or impossible to place weight on the foot.
Joints of the upper limbs are less frequently involved, and their possible involvement causes problems for differential diagnosis.
During an acute attack, the patient may have a slightly elevated body temperature.
Initially, the arthritis will resolve within a few days or in no more than a couple of weeks.
In a typical case, the diagnosis can be based on the clinical picture. A history of paroxysmal joint symptoms or high plasma urate levels support the diagnosis.
The diagnosis of gout is confirmed if a sample taken from an inflamed joint shows monosodium urate (MSU) crystals partly phagocytosed by leucocytes (picture F2). For the preparation of synovial fluid samples for dispatch, see Investigation of Synovial Fluid.
The leucocyte count in synovial fluid is elevated (even over 50 000 × 106 /l) with a predominance of granulocytes.
During a gout attack, plasma urate concentration is often low.
A high urate concentration and unspecific joint complaints do not confirm the diagnosis of gout.
Arthrosis Osteoarthritis of the Hip and Knee, erysipelas Erysipelas, pseudogout, purulent arthritis, seronegative spondyloarthropathy and palindromic rheumatism should be considered in differential diagnosis.
Chronic gout
Untreated, acute intermittent gout may become chronic.
Gout attacks become more frequent and longer and, finally, joints may be painful and swollen between attacks.
Tophi (subcutaneous accumulation of sodium urate) may occur particularly in fingers, wrists, ear lobes or extensor aspects of the limbs. Skeletal tophi may be associated with neurological symptoms (paresis).
A patient may have bursitis, tendinitis, cellulitis and urolithiasis.
Chronic pyrophosphate arthropathy is often asymptomatic, or the clinical picture may resemble arthrosis of large joints.
Hyperparathyroidism Hypercalcaemia and Hyperparathyroidism (picture F4) and haemochromatosis Haemochromatosis make patients susceptible to pseudogout. These diseases should be ruled out, especially in patients under 60 years of age.
Gout and purulent arthritis should be considered in differential diagnosis of acute pseudogout; in chronic disease, rheumatoid arthritis Rheumatoid Arthritis as well as arthrosis.
Laboratory test
ESR, CRP
Reflect the severity of the inflammatory reaction.
Oral glucocorticoids are used increasingly often, particularly in cases with relative contraindications for anti-inflammatory analgesics (abdominal discomfort, renal or cardiac failure, hypertension).
The initial dose of prednisone (or prednisolone) is 20-40 mg/day for about 3-5 days. The medication should then be reduced and withdrawn within 1-2 weeks.
If NSAIDs and glucocorticoids are contraindicated, interleukin-1 inhibitors (anakinra, canakinumab) have also been used to alleviate severe gout attacks. These medicines are very expensive and they are not officially indicated in the treatment of gout.
Colchicine can also be used to treat acute gout if other medicines are not suitable.
The recommended dose is two 0.5 mg tablets to start with and one more after an hour.
Later 0.5 mg three times a day until the attack eases, but not a course of more than 12 tablets.
Medication can be recommended after the first gout attack already, if the patient is less than 40 years of age or if the urate concentration is clearly increased (> 480 µmol/l) or if the patient has associated diseases.
Antihyperuricaemic medication in gout patients may lower blood pressure, improve the prognosis of cardiovascular diseases and slow down the worsening of renal failure.
Medication of an asymptomatic patient may be individually considered, if the urate concentration is considerably high (particularly in renal failure).
The most common adverse effects are abdominal discomfort, rashes, elevated liver enzyme values and hypersensitivity reactions. The prevalence of a severe hypersensitivity syndrome is 0.1-0.4%. Agranulocytosis is rare.
In patients with renal insufficiency, the aim of the treatment is the same. At GFR levels > 20 ml/min normal doses, at 10-20 ml/min 100-200 mg/day and in terminal uraemia 100 mg once daily or 300 mg after dialysis.
Allopurinol is started in haematological patients on cytotoxic medication when beginning treatment.
The initial dose is 80 mg/day. A response can be seen as soon as after 2-4 weeks, and the dose should be increased, depending on the therapeutic target, up to 120 mg/day.
Used if allopurinol is not suitable or sufficiently effective.
The most common adverse effects are abdominal discomfort, rashes and hypersensitivity reactions.
The dose need not be reduced if GFR > 30 ml/min. In severe renal insufficiency, lower doses should be used, depending on the therapeutic target.
Xanthine oxidase inhibitors can also be started during an effectively treated acute gout attack, and existing medication with xanthine oxidase inhibitors should not be interrupted during an attack.
Can be used (also in combination) if xanthine oxidase inhibitors are not suitable or sufficiently effective.
Initial dose 250 mg twice daily, after two weeks 500 mg twice daily. In the beginning of treatment urine should be alkalized (pH > 6) with 1 g sodium bicarbonate 3-4 times daily for at least one month.
In acute intermittent gout, antihyperuricaemic medication can be interrupted after one year after due consideration. In some patients, serum urate levels can be kept on target by lifestyle changes and dietary treatment.
In chronic gout, very long-term or permanent medication will be needed.
A short course of oral glucocorticoids can be used for severe attacks, particularly if affecting several joints (see treatment of acute gout).
The treatment of chronic pseudogout is symptomatic (paracetamol and anti-inflammatory analgesics, as necessary). Arthrosis should be treated conservatively.
In treatment-resistant situations, interleukin-1 blockers (expensive, may not be reimbursable) or methotrexate may be considered.
Follow-up of gout
The treatment and regular follow-up of gout should be done mainly in primary health care.
Treatment target: plasma urate < 360 µmol/l
Assessment in specialized care is warranted in patients with unclear diagnosis or refractory gout.
After starting antihyperuricaemic medication, follow-up in 2-3 months, checking at least basic blood count with platelet count, ALT, creatinine (GFR Gfr Calculator), urate
Further follow-up examinations every 6-12 months
References
Fields TR. The Challenges of Approaching and Managing Gout. Rheum Dis Clin North Am 2019;45(1):145-157 [PubMed]
Drug and Therapeutics Bulletin. Latest guidance on the management of gout. BMJ 2018;362:k2893. [PubMed]
Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76(1):29-42. [PubMed]
Singh JA, Yu S. Are allopurinol dose and duration of use nephroprotective in the elderly? A Medicare claims study of allopurinol use and incident renal failure. Ann Rheum Dis 2017;76(1):133-139. [PubMed]
Neogi T, Jansen TL, Dalbeth N, et al. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2015;74(10):1789-98. [PubMed]