Disease process
Uric acid (monosodium urate) is a compound that is naturally produced and removed by the body. If the rate of production of uric acid exceeds the rate of removal, the concentration of uric acid in the blood can rise above desirable levels (hyperuricaemia). Uric acid normally remains dissolved in the blood stream but as the concentration of uric acid increases it becomes less soluble. Other factors, including temperature and pH (acidity or alkalinity of a watery solution) influence the solubility of uric acid and, under specific conditions, needle-shaped crystals can form in and around a joint, triggering an inflammatory response.
A simple analogy of the crystal formation process would be to imagine sugar in a cup of boiled water. Initially the sugar will dissolve in the fluid but as more is added it will no longer dissolve and the sugar will collect at the bottom of the cup. The sugar is less likely to dissolve if the water is cold, which may explain why ‘colder’ joints such as the big toe are more susceptible to gout.
Risk factors
Gout is more common in males, postmenopausal women, some ethnic groups (Taiwanese, Aboriginies, Māori and Pacific Islanders), and is more common in older individuals. High consumption of purine-rich food or drink (e.g. offal, meat, certain seafood, sugar sweetened drinks, beer and spirits) have been associated with gout, as purines are broken down into uric acid by the body.
Presentation
In the first episode of gout, signs and symptoms of inflammation (pain, swelling, heat, redness and difficulty moving the joint) typically present in one joint only (monoarthritis), peak within 24 hours and resolve completely within 1-2 weeks of onset. The big toe is the most commonly affected joint but subsequent episodes can involve multiple joints (polyarthritis) including the knee, may occur more frequently, and take longer to settle. In long-standing cases (chronic gouty arthritis), the affected joint may become structurally damaged and small ‘chalk-like’ lumps (tophi) can develop beneath the skin.
Diagnosis
Definitive diagnosis of gout requires the identification of crystals in samples of fluid (or tophi) taken from the affected joint. Fluid is withdrawn from the affected joint via a needle (joint aspiration) and analysed with polarising light microscopy to confirm the presence of monosodium urate crystals. These samples should be analysed immediately at room temperature as formation and solubility of crystals are affected by temperature and pH. The sample should also be assessed for the presence of bacteria by performing gram stain and culture as gout and joint infection can present with similar signs/symptoms and the conditions can co-exist.
If it is not possible to assess fluid or tophi samples, other tests may be performed to determine the likelihood of gout. Blood tests can measure the concentration of uric acid in the blood (serum urate), inflammatory markers (e.g. C-reactive protein) and markers of infection (full blood count). It is important to note that these tests cannot be used to definitively diagnose gout as some patients will have elevated serum urate levels but do not develop symptoms, while one third of patients will have normal serum urate levels during a confirmed flare up. However, gout is unlikely in an individual with a serum urate level persistently below 360μmol/L (6.05mg/dL), as crystals do not usually form below this level.
Serum urate levels can be combined with other clinical signs/symptoms to determine the probability of gout by using the gout calculator; points are awarded if the criteria below are present. Elevated temperature (fever), C-Reactive protein and white blood cell levels may indicate infection, but in acute flare ups of gout or CPPD disease, these levels may also be raised, especially when multiple joints are involved.
Imaging
X-rays may be normal in early stages of gout but bone erosion may be evident in advanced stages. Ultrasound and CT scans have more recently been utilised to identify urate deposition, and therefore aid the diagnosis of gout.
Treatment
Acute flare-ups of gout should be managed with medication (e.g. non-steroidal anti-inflammatories (NSAIDs), corticosteroid or colchicine), as prescribed by a qualified health care professional. There is no evidence to suggest that either oral NSAIDs or corticosteroid injections are superior for pain relief during acute flare-ups of gout but corticosteroids appear to be safer.
Strategies that achieve crystal dissolution are central to the effective management of gout. Urate lowering medication (e.g. Allopurinol, Feboxustat) may be prescribed by a qualified health care professional, with a target serum urate level of <360umol/L. Lifestyle changes are also recommended as alcohol consumption, poor diet and obesity have been associated with a poor response to urate lowering medication.
In advanced cases, knee joint replacement may be indicated for individuals with symptomatic gout that is not responding appropriately to conservative treatment.
Signposting
Individuals presenting with a first episode of sudden onset (within 24 hours) heat, swelling and pain in the knee, with no history of injury, should attend Accident and Emergency immediately to exclude an infection in the joint (septic arthritis).
Patients that have had a previous episode of similar symptoms, which was diagnosed as inflammatory arthritis, may have a flare up and can contact their GP or rheumatologist immediately. However, a previous diagnosis of inflammatory arthritis does not exclude the possibility of joint infection; therefore, the patient should attend Accident and Emergency immediately if there is any doubt as a delay in diagnosis can have serious consequences.
Written by: Richard Norris
Peer reviewed by:
Dr Paul Kirwan (PhD) | @pdkirwan
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