Gout: Treat to Target to Prevent Irreparable Joint Damage

Dr Louise Warburton Reviews the NICE Guideline on Gout, Which Stresses the Importance of Effective Diagnosis, Management of Flares, and Urate-Lowering Therapy

Gout is an acute crystal arthropathy characterised by the deposition of urate crystals within joints, which can cause sudden flares of pain, heat, and swelling.^1,2 Gout develops rapidly, often overnight;¹ the attack usually peaks after 12–24 hours,³ and typically presents in distal joints such as the first metatarsophalangeal (MTP) joint.^1,4 The patient’s pain tends to be acute, to the point that even the pressure of a blanket on their foot can be too much to bear.^1–3

Gout is more common in men than in women, occurring most frequently in men aged over 30 years and in postmenopausal women.¹ In 2012, the prevalence of gout in the UK was calculated to be 2.49%, a significant rise compared with its prevalence in 1997,⁵ and one in 14 men and one in 35 women are thought to be affected by the condition according to the UK Gout Society.² Treatment for gout is often suboptimal—in 2012, fewer than half of patients with gout were being consulted specifically for gout, and just over one-third were receiving the appropriate treatment.⁵ The disease is usually managed in primary care without specialist rheumatological input,¹ so it is essential that primary care clinicians are able to treat it effectively.

This article explores NICE Guideline (NG) 219, Gout: diagnosis and management, the first guideline on gout to be published by NICE.¹

Diagnosis

A diagnosis of gout is made based on the patient’s history and a clinical assessment¹ —there are no investigations that can be done routinely at the bedside that can help a practitioner to decide if gout is the cause of a patient’s pain.

Besides the usual symptoms, the patient may also have low-grade pyrexia, loss of appetite, or fatigue.² Gouty tophi may also present around the affected joint or elsewhere on the body, which can aid diagnosis^1,3 —although, in my experience, they are not common when a patient first presents.

Differential Diagnoses

It is important to consider other possible diagnoses that present in a similar way to gout.¹

Septic Arthritis

A single painful, hot, or swollen joint with restricted movement can be caused by septic arthritis.^6–8 Consider the risk factors for septic arthritis when assessing the patient, which include old age, comorbidities (such as rheumatoid arthritis), infection in another part of the body (such as gonorrhoea), prosthetic joints, and immunosuppression.^7,9 Patients with septic arthritis may have a raised temperature,⁹ but this is also true of patients with gout.²

If there is any suspicion of septic arthritis, admit the patient immediately via the local care pathway, which may be through Orthopaedics or Rheumatology.¹ Patients with symptoms of septic arthritis should be regarded as having the infection until it is proven otherwise.^7,8 The British Society for Rheumatology provides some excellent guidance on rheumatological conditions, including gout and hot swollen joint, at bit.ly/3dtYky0.^8,10

Pseudogout

Pseudogout, also known as calcium pyrophosphate dihydrate deposition (CPPD) disease, is an acute arthritis caused by the deposition of CPPD crystals in joints.¹¹ It tends to favour larger joints, such as the knees or wrists,^11,12 and is common in people aged over 60 years.¹¹

The condition can be very painful, and the joint may be red and similar in appearance to gout, but pseudogout often has a slower onset.¹² If it is possible to aspirate the affected joint, CPPD crystals may be seen in the synovial fluid.¹¹

Trauma

Trauma can cause redness and pain in a joint.⁶ Injury to a joint can also trigger an attack of gout.¹³

Inflammatory Arthritis

Also consider inflammatory arthritis when a person presents with symptoms of gout, particularly in atypical presentations of swelling and pain in multiple joints.¹ Rheumatoid arthritis and psoriatic arthritis can both present with inflammation and pain in just one joint or digit (see NG100, Rheumatoid arthritis in adults: management,¹⁴ and NG65, Spondyloarthritis in over 16s: diagnosis and management¹⁵). In general, however, these types of arthritis will have a slower onset, unlike the typical overnight development of acute gout. If inflammatory arthritis is suspected, refer urgently for a rheumatological opinion.

Diagnostic Investigations

A clinician may decide that further investigations are needed to determine a diagnosis of gout. NG219 recommends:‘Measure the serum urate level in people with symptoms and signs of gout … to confirm the clinical diagnosis (serum urate level of 360 micromol/litre [6 mg/dl] or more). If serum urate level is below 360 micromol/litre (6 mg/dl) during a flare and gout is strongly suspected, repeat the serum urate level measurement at least 2 weeks after the flare has settled.’¹

In practice, it is unlikely that a blood test for gout would be taken on the same day that a patient presents, unless they have been admitted to hospital or sepsis is suspected. In my experience of primary care, arrangements are usually made to perform blood tests when the next phlebotomy appointment is available, which may be a couple of weeks later. By this time, the patient’s serum urate level will likely have settled and be more straightforward to interpret.¹

It will also be possible to use these blood tests as an opportunity to assess the patient for the following comorbidities of gout, which are components of metabolic syndrome:^16,17

• type 2 diabetes
• hypertension
• dyslipidaemia
• obesity
• increased cardiovascular risk.

It is important to assess these comorbidities in each new patient presenting with gout;¹ cardiovascular risk is increased in all patients with metabolic syndrome,¹⁷ and these patients can be advised about addressing the risks. There is important prevention work to be done with each new case of gout—NG219 refers clinicians to NICE Clinical Guideline 181, Cardiovascular disease: risk assessment and reduction, including lipid modification,¹⁸ when considering cardiovascular risk factors.¹

NG219 advises clinicians to consider aspirating the affected joint and assessing the synovial fluid microscopically for infection and urate crystals, particularly when a diagnosis of gout remains uncertain or unconfirmed.¹ In principle, this may be helpful for diagnosis, and can also relieve pain in an intensely swollen joint; however, it is quite difficult to accomplish in a small joint such as the first MTP joint.¹ In my experience, finding urate crystals is not easy—I can only think of a couple of patients in whom I have successfully demonstrated the presence of urate crystals through joint aspiration.

If the diagnosis is in doubt or if joint aspiration cannot be undertaken, NG219 suggests imaging the joint.¹ An X-ray can demonstrate coexisting osteoarthritis and long-term damage to the affected joint,^1,19 which may be helpful because gout is more common in damaged joints.²⁰ Ultrasound can also help to rule out other forms and causes of synovitis, such as rheumatoid arthritis,²¹ but it is often hard to obtain and waiting lists can be very long. Therefore, in practice, I tend not to refer patients for imaging at the time of diagnosis.

A review of medications the patient is taking is also recommended at diagnosis,¹ as some drugs—particularly some diuretics—can raise serum urate level.^1,22,23 Thiazide diuretics are particularly liable to cause a rise in serum urate level,^23,24 but most diuretics have the potential to do this.^22,23

Information and Support

Once a diagnosis has been made, and in subsequent follow-up appointments, NG219 recommends providing tailored information to people with gout and their family members or carers (as appropriate), explaining the areas outlined in Box 1.¹

It can be easy to omit this part of the management plan, but if a patient does not understand that gout is a chronic condition that can cause irreversible joint damage, they are unlikely to continue with their urate-lowering therapy (ULT).^1,5

Managing Gout Flares

Gout is characterised by flares, which are often what first prompt a patient to see a healthcare professional.

Flares can be caused by starting or increasing a patient’s dose of ULT.^1,25–27 This is important, as it can lead people to stop their ULT. Advise patients not to cease ULT, but to continue with it and manage their symptoms with another treatment, such as a nonsteroidal anti-inflammatory drug (NSAID), colchicine, or a short-term steroid.¹ If a patient decides to manage their ULT-related gout flares with one of these medications, NG219 recommends colchicine first line, with a low-dose NSAID or low-dose oral corticosteroid if this is not tolerated or ineffective (note: at the time that NG219 was published, this was an off-label use of NSAIDs and oral corticosteroids).¹ A proton-pump inhibitor can also be considered for people with gout taking an NSAID or corticosteroid for this purpose.¹

Flares can be caused by dehydration,¹³ and also by trauma resulting from strenuous exercise, which can bring about mechanical shedding of urate crystals into the joints.²⁸ In addition, going on holiday, particularly if flying or travelling to a hot or humid country,²⁹ can precipitate a flare.

Simple measures, such as ice packs^1,13 and elevation of the affected limb,¹³ can also be effective for managing flares.

Follow Up After Gout Flares

Seeing a patient just after a flare can help to reinforce the importance of continuing with ULT and reducing cardiovascular risk. NG219 suggests considering a follow-up appointment after a gout flare has settled, so that a practitioner can:¹

• measure the patient’s serum urate level
• provide information about gout and how to self-manage and reduce the risk of future flares (see the section Information and support in NG219)
• assess the patient’s lifestyle and comorbidities (including cardiovascular risk factors and chronic kidney disease [CKD])
• review medications and discuss the risks and benefits of long-term ULT.

An assessment of a patient’s lifestyle should take diet into consideration. A high-purine diet, which includes foods such as red meat, oily fish, seafood, and offal, can cause a rise in serum urate level,^2,3,13,30 as purines are metabolised into urates; therefore, maintaining a low-purine diet may be an effective way of reducing gout flares.³⁰ Obesity and excess alcohol intake can also exacerbate gout flares.¹ More information on diet and gout can be found on the UK Gout Society’s website (bit.ly/3p0GJQX),³⁰ although the Guideline Development Group for NG219 states that there was insufficient evidence to support any specific dietary recommendations.¹

When following up after a gout flare, a review of medication is recommended, as it is at diagnosis, to identify any drugs that can raise serum urate level.¹

Long-Term Management of Gout

NICE’s recommendations for the long-term management of gout with ULT are summarised in Figure 1.³¹

Initiating ULT

Assessing when to start ULT can be challenging. NICE suggests offering ULT, as part of a treat-to-target strategy, to people with gout who have any of the signs and symptoms listed in Box 2.¹

Patients in these categories should be offered ULT and start it as soon as they can, as they are at risk of long-term problems or chronic gout, both of which can cause irreversible joint damage.¹

For people who are experiencing their first attack of gout but are not in one of the high-risk categories shown in Box 2, NICE recommends discussing ULT and offering it in a treat-to-target regimen as part of a shared decision-making consultation with the patient.¹ Some patients will choose not to start ULT at this point; regardless, NICE recommends repeating the discussion if they have a subsequent attack of gout.¹ It is important to offer ULT each time the patient attends.¹

Treat-to-Target ULT

‘Treat to target’ ULT is a new concept introduced in NG219 whereby practitioners monitor a patient’s serum urate level—ideally on a monthly basis—and increase ULT doses accordingly, as tolerated, until this level is below an agreed-upon threshold.¹ NICE suggests a target level of 360 micromol/l for most patients,¹ which is below the saturation point of uric acid (approximately 404 micromol/l).³² Once the serum urate level falls below this point, urate crystals will start to dissolve into solution out of joints, and will subsequently be excreted via the kidneys. A lower target serum urate level of 300 micromol/l is recommended for people with tophi or chronic gouty arthritis, and for those who have troublesome flares despite a serum urate level below 360 micromol/l.¹

Traditionally, patients were started on ULT and given no follow-up appointments unless their gout flared up again; in many cases, patients remained on suboptimal doses of ULT or stopped following their ULT programme altogether because of a perceived lack of benefit.⁵ In a 2012 study, only around 40% of patients living with gout who received ULT adhered to their treatment regimen.⁵ Therefore, the treat-to-target approach is an exciting new concept for gout, as it may help to prevent this suboptimal treatment.

First-line ULT is either allopurinol or febuxostat, both of which require slow uptitration, as tolerated, to avoid triggering a flare.¹ Febuxostat is contraindicated in people with cardiovascular risk factors, such as unstable angina or stroke.^1,33 It is particularly important to start allopurinol at a lower dose and uptitrate gradually to avoid a serious hypersensitivity reaction that, although rare, can be extremely dangerous.^25,34,35 This hypersensitivity reaction generally presents as fever, eosinophilia, hepatic and renal dysfunction, and rash.^25,35

It is recommended that clinicians measure a patient’s serum urate level every month until the target is reached, then annually along with other cardiovascular risk indices.¹

Preventing Gout Flares When Starting or Uptitrating ULT

As mentioned in the section Managing gout flares, it is likely that starting or uptitrating ULT will cause a flare.^1,25–27 It is important to warn the patient about this, and explain the benefits of continuing therapy.¹

Flares can be treated with colchicine, NSAIDs, or short-term corticosteroids, as outlined in the section Managing gout flares.¹

Referral to Specialist Services

NG219 recommends referring patients to specialist services, such as Rheumatology, when:¹

• the diagnosis of gout is uncertain
• treatment is contraindicated, not tolerated, or ineffective
• the patient has CKD of stages 3b–5 (glomerular filtration rate categories G3b–G5); this is because higher doses of ULT can cause toxicity, and the dose of allopurinol must be lowered to accommodate this
• the patient has had an organ transplant.

Conclusion

Gout is a disease that is routinely managed in primary care; therefore, it is important that the condition and its treatment are properly understood by primary care practitioners. Accurately and effectively diagnosing, treating, and educating patients with gout will help to increase their willingness to start and adhere to ULT, thereby reducing the number of flares they experience, and preventing long-term damage to the affected joints.

Dr Louise Warburton

GPwER in rheumatology, Associate Medical Director of Shropshire Community Health NHS Trust