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Gout and Pseudogout
Essentials
- Gout and pseudogout (chondrocalcinosis, pyrophosphate arthropathy) are common disorders causing arthritis in one or few joints.
- A synovial fluid sample should be taken whenever gout (sodium urate crystals) or pseudogout (pyrophosphate crystals) is suspected..
- Acute arthritis in a patient with arthrosis of large joints may be due to pseudogout requiring topical treatment with a glucocorticoid and anti-inflammatory analgesics.
- Brief oral courses of glucocorticoids are increasingly used for the treatment of acute gout, and treatment can be intensified by topical intra-articular injections.
- 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.
- Hyperuricaemia also occurs in patients with skin psoriasis Psoriasis or haematological diseases (such as CML Chronic Myelogenous Leukaemia (CML)).
- Gout rarely occurs in premenopausal women or men below 25.
- In pseudogout, calcium (calcium pyrophosphate) accumulates in articular cartilage and menisci 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
- The typical symptom is sudden nocturnal onset of redness, heat, pain and swelling of the first metatarsophalangeal joint of the big toe. 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 sodium urate crystals partly phagocytosed by leucocytes. 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 levels are often low.
- High urate levels 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.
- X-ray pictures may show clearly defined joint erosions http://www.dynamed.com/condition/gout#X_RAY.
- Accumulation of sodium urate in tissues (often subclinical) can also be detected by ultrasonography, MRI or dual-energy CT http://www.dynamed.com/condition/gout#DUAL_ENERGY_COMPUTED_TOMOGRAPHY__DECT_.
- Rheumatoid arthritis Rheumatoid Arthritis and seronegative spondyloarthropathies should be considered in differential diagnosis.
Laboratory test
- ESR, CRP
- Reflect the severity of the inflammatory reaction.
- Urate
- Creatinine (GFR Gfr Calculator)
- Renal insufficiency predisposes to gout and affects the choice of treatment.
- Cholesterol, cholesterol-LDL, cholesterol-HDL, triglycerides, HbA1c and/or fasting blood glucose
- Cardiovascular diseases and their risk factors are associated with gout.
- Metabolic syndrome (obesity, hypertension, type 2 diabetes, hyperlipidaemia), cardiac and renal failure, venous obstructive disease (cardiac, cerebral, peripheral), smoking
- Basic blood count with platelet count, ALT
- As part of the follow-up of the pharmaceutical treatment of gout.
- Ionised calcium, transferrin saturation
- Hyperparathyroidism and haemochromatosis predispose patients to pseudogout.
- Synovial fluid sample (cells and crystals), see Investigation of Synovial Fluid
Treatment
- Rest, cold and anti-inflammatory analgesics in sufficient doses (not aspirin)
- 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 30-40 mg/day for about 3-5 days. The medication should then be reduced and withdrawn within 1-2 weeks.
- The response to treatment can be intensified by giving topical intra-articular methylprednisolone.
- All the above treatments can be combined.
- If NSAIDs and glucocorticoids are contraindicated, interleukin-1 inhibitors (anakinra, canakinumab, rilonacept) 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 is a medicine available for compassionate use, only, and not too often used in Finland. Larger doses easily cause diarrhoea.
Dietary treatment and lifestyle modification
- Antihyperuricaemic medication is indicated in the treatment of chronic gouty arthritis, tophi, urolithiasis and recurrent acute gout attacks http://www.dynamed.com/condition/gout#PREVENTION_OF_RECURRENT_ATTACKS.
- 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 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).
- It should be assessed whether diuretics can be withdrawn and replaced by other medication, such as a calcium-channel blocker, ACE inhibitor or ATR blocker (losartan is uricosuric http://www.dynamed.com/management/gout-management-prevention-of-recurrent-attacks#LOSARTAN).
- Antihyperuricaemic medication is used to
- Allopurinol
- Febuxostathttp://www.dynamed.com/management/gout-management-prevention-of-recurrent-attacks#FEBUXOSTAT
- 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.
- Should not be combined with azathioprine, mercaptopurine or theophylline.
- 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.
- After starting xanthine oxidase inhibitors gout attacks may become more frequent for 3-6 months, during which time anti-inflammatory analgesics, short courses or low maintenance doses (e.g. 5-10 mg once daily) of prednisone, or colchisine at dose 0.5 mg 2 or 3 times daily http://www.dynamed.com/management/gout-management-prevention-of-recurrent-attacks#CHOICE_OF_ULT_REGIMEN can be used.
- Probenecidhttp://www.dynamed.com/management/gout-management-prevention-of-recurrent-attacks#PROBENECID
- 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.
- Prescription: sodium bicarbonate 1 g, 100 tablets; extemporaneous prescription
- Allergic reactions are the most common adverse effects.
- Should not be used in patients with a history of urolithiasis or with GFR < 50 ml/min.
- Benzbromaronehttp://www.dynamed.com/management/gout-management-prevention-of-recurrent-attacks#BENZBROMARONE
- Initial dose 50 mg once daily, maintenance dose 100-200 mg once daily.
- The most common adverse effects are allergic reactions and elevated liver enzyme values.
- Should not be used in patients with a history of urolithiasis.
- Can be used in patients with renal insufficiency with GFR > 20 ml/min.
- Probenecid and benzbromarone are available with special permission (not reimbursable).
- Rasburicasehttp://www.dynamed.com/management/gout-management-prevention-of-recurrent-attacks#RASBURICASE
- Used in special indications in specialized care.
- Ascorbic acid (vitamin C, 500 mg once daily) lowers uric acid levels by 50-100 µmol/l.
- 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.
Follow-up of gout
- The treatment and regular follow-up of gout should be done mainly in primary health care.
- 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), urate
- Further follow-up examinations every 6-12 months
References
- 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]
- 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]
- Drug and Therapeutics Bulletin. Latest guidance on the management of gout. BMJ 2018;362:k2893. [PubMed]
Evidence Summaries ⬆