Gout is the most common form of inflammatory arthritis.1 It is caused by monosodium urate crystals accumulating
in joint fluid, cartilage, bones, tendons and other tissues.2 Urate is produced via the metabolism of dietary
and endogenous purines.3 When urate levels in the blood reach saturation point, monosodium urate crystals
can form. The inflammatory response to these crystals results in gout flares which are characterised by painful, red,
hot, swollen joints. Over time, the duration and frequency of these flares may increase, resulting in chronic gouty arthritis
and subcutaneous deposits of crystals referred to as tophi, both of which can lead to the destruction of joints.2
The risk factors for gout
Long-term hyperuricaemia is the most important risk factor for the development of gout, and in many patients this will
be caused by declining renal function.1 Detecting chronic kidney disease (CKD) early and preserving renal
function is therefore an important gout-prevention strategy. Additional factors that contribute to hyperuricaemia, and
are associated with an increased risk of developing gout, include increasing age, male sex, hypertension, obesity, use
of diuretics, antihypertensive medicines and low dose aspirin and excessive consumption of red meat, seafood, beer, spirits,
sucrose or fructose-sweetened drinks.1
The burden of poorly-controlled gout is often over-looked
Gout is much more than an intensely painful condition that prevents people from working, performing daily activities
and participating in their communities.4 People with gout are also more likely than those without gout to
die at a younger age due to cardiovascular and renal complications.1 In New Zealand, 40% of people with gout
have diabetes and/or cardiovascular disease.5 Despite this, many patients consider gout to be a condition
that merely requires analgesics to control and are not aware of the potential long-term consequences.6 Raising
community awareness about gout is an important role for health professionals in primary care.
Urate-lowering treatment improves long-term health outcomes
Reducing serum urate levels in patients with gout not only means that gout flares are less likely, it may also help reduce
the risk of adverse renal and cardiovascular outcomes. For example, a meta-analysis found that compared to patients who
were not taking a urate-lowering medicine (or were taking a placebo), patients with hyperuricaemia and CKD who were taking
a urate-lowering medicine:7
- Reduced their risk of cardiovascular events or renal failure by more than half
- Had slower rates of decline in renal function
- Reduced their proteinuria
A recent study found that patients with gout and diabetes who were taking urate-lowering treatment had significantly
lower risk of myocardial infarction or stroke.8
Māori and Pacific peoples with gout are not receiving adequate care
Gout management in New Zealand needs to change because Māori and Pacific peoples, in particular, are not receiving the
medicines they need to manage their health effectively. Furthermore, research suggests that disparities between how gout
is managed in Māori and non-Māori is ingrained in the current model of care, with no reduction in the disparity between
2006/7 and 2012/13.9
Gout is more frequent and more severe in Māori and Pacific patients
The prevalence and burden of gout in New Zealand is higher in Māori and Pacific patients than in other groups. In 2014,
7.6% of Māori and 12.7% of Pacific peoples aged over 20 years were identified as having gout, compared to 4% of people
of New Zealand European or Asian descent.10 The prevalence of gout increases with age; among males aged over
65 years the prevalence is 36.7% for Māori, 46.0% for Pacific peoples and 16.5% for people of New Zealand European or
Asian descent.10 Māori patients with gout are dispensed more prescriptions for NSAIDs each year (60%) than
New Zealand European-Other patients with gout (54%) and are therefore at greater risk of NSAID-related adverse effects,
e.g. acute kidney injury and cardiovascular events.10 Māori and Pacific patients with gout are also five
times more likely to be admitted to hospital due to gout than people of New Zealand European or Asian descent.10
Māori and Pacific patients with gout are often under-treated
Figure 1 shows that in 2017, 3.4% of Māori and 4.8% of Pacific patients were dispensed a urate-lowering medicine, compared
to 2.2% of New Zealand Europeans.11 However, the prevalence of gout is approximately twice as high in Māori
and more than three times higher in Pacific peoples, compared to New Zealand European and Asian peoples.5 These
results strongly suggest that gout in both Māori and Pacific peoples is under-treated.
Figure 1: Percentage of enrolled patients dispensed allopurinol, benzbromarone, febuxostat or probenecid from a community
pharmacy in New Zealand by ethnicity in 2017, compared to prevalence of gout in patients aged over 20 years in 201410, 11
Numerous studies from New Zealand and overseas show that urate-lowering treatment is often delayed well beyond the point
when it is indicated. For example, a small qualitative study of Māori patients with gout found that on average urate-lowering
treatment was not prescribed until 18 years after the appearance of symptoms.4 In the United Kingdom, a study
of more than 52,000 patients with gout found that one year after diagnosis only 17% had a prescription for a urate-lowering
medicine, at five years this had risen to 30%, and after ten years only 41% of patients had a prescription for a urate-lowering
medicine.12 A systematic review assessing the management of gout in primary care found that the proportion
of patients with gout who were taking urate-lowering medicines was variable, depending on the study. However, six out
of eight of the most robust studies found that less than 50% of patients with gout were taking urate-lowering treatment.13
Once urate-lowering medicines are started, monitoring is also often sub-optimal, meaning that many patients will still
have serum urate concentrations above recommended levels for treating gout. A systematic review found that in one study,
one-quarter of patients received a serum urate test in the first six months of urate-lowering treatment, and in another
study, only one-third of patients had been tested after the first year of urate-lowering treatment.13
The barriers to the early and optimal use of urate-lowering medicines are multi-factorial. Firstly, there is a lack
of clarity in guidelines as to the best time to initiate treatment, and at times there are discrepancies between guidelines.
Secondly, there is sometimes a perception among health professionals that gout management is acute, rather than preventative.14 The
limited time that is available in consultations in primary care and the intermittent nature of gout flares also make it
difficult for health professionals to focus on the long-term management of gout.14
Nurses and pharmacists have an important role in gout management
Most patients with gout are able to achieve serum urate targets if they are provided with effective support. This role
is ideal for nurses in primary care; an essential component of gout education is overcoming misconceptions that are barriers
to care (see below). A nurse-led programme in primary care in the United Kingdom found that with education and lifestyle
advice, 92% of patients were able to achieve serum urate treatment targets.15
Community pharmacists can reduce delays in the diagnosis of gout and the initiation of urate-lowering treatments by
asking patients who are purchasing NSAIDs about their symptoms. Patients who may have gout, e.g. those with a history
of gout-like flares, can be encouraged to present to general practice for an assessment, and those who know they have
gout can be encouraged to discuss the possibility of starting urate-lowering treatment with a general practitioner.
Owning My Gout is a project involving community pharmacists and practice nurses in South Auckland. An electronic shared-care
plan is initiated by a practice nurse, and community pharmacists use Standing Orders for titrating allopurinol in collaboration
with the General Practice team. Further information is available from:
http://koawatea.co.nz/wp-content/uploads/2015/06/LS4-Manaaki-Hauora-Project-Review-Owning-My-Gout-March-2016.pdf
Overcoming misconceptions that are barriers to managing gout
Perceptions and beliefs about gout can contribute to delays in initiating urate-lowering treatment.6 Good
communication helps to overcome misconceptions that are barriers to care. A structured approach to discussions is therefore
recommended:
- Assess the patient’s understanding about gout
- Build on their knowledge by validating information that is correct, filling in knowledge gaps and correcting misconceptions
- Check that the patient has understood the information that has been delivered
The goal is to form a loop of communication, with gaps in understanding forming the basis for further discussion.
Further information on effective discussion and communication about gout management with patients is available from
www.bpac.org.nz/bpj/2014/april/gout.aspx
Delivering the messages that patients and whānau need to hear
Do not blame yourself because you have gout. Gout is a multi-factorial condition that is not solely caused
by lifestyle factors. Genetic variations in uric acid renal transporters contribute significantly to the ethnic differences
in gout prevalence.16 Explaining to Māori and Pacific patients that they may have a genetic predisposition
to gout helps to dispel the perception that the condition is self-inflicted.
Gout is serious, it’s not just “a pain in the toe”. By actively managing their condition, e.g. making lifestyle
changes and maintaining treatment adherence, patients with gout can reduce their risk of cardiovascular and renal complications.
Gout is a long-term disease caused by deposits of urate crystals.These crystals are still present in the
joint after a flare has settled. The crystals will only dissolve if the urate level in the blood is kept low (< 0.36
mmol/L) by medicines such as allopurinol.
In the long-term, allopurinol can stop flares from happening. If patients adhere to urate-lowering treatment
and serum urate levels are treated to target, flares of gout will be virtually eliminated for many patients within two
years.17
Allopurinol is a safe and highly effective medicine. Urate-lowering medicines such as allopurinol are associated
with an increased risk of flares in the first months of treatment and this may discourage some patients to take them,
even if they have collected the prescription from the pharmacist.4 Patients can be reassured that with prophylactic
medicines and appropriate dose titration, the risk of allopurinol causing a flare will be substantially reduced and ongoing
adherence to treatment will prevent future flares.
Patient resources for gout, including Samoan and Tongan language versions, are available from:
www.goodfellowunit.org/gout-study-project/gout-study-project
In primary care, gout is usually diagnosed clinically with supporting evidence provided by elevated serum urate levels;
see “Diagnosing gout” for an example of a validated diagnosis tool and alternative diagnoses to consider.18
Caution is required when interpreting serum urate levels during a gout flare as up to 40% of patients are reported to
have serum urate levels within the normal range;19 repeat testing for diagnostic purposes may be required
once the flare has subsided. Although the gold standard for diagnosing gout is the presence of monosodium urate crystals
under polarised microscopy,1 joint aspiration is usually not necessary unless there is a high suspicion of
another cause, e.g. septic arthritis.
Best practice tip: Request a renal function test at the same time as the serum urate to allow for the prompt initiation
of urate-lowering treatment, should a diagnosis of gout be confirmed
Diagnosing gout
Table 1 provides an example of a scoring system for the clinical diagnosis of gout. A score of eight or more is associated
with a greater than 80% likelihood of gout.18 A score of four or less rules out gout in almost 100% of patients
and an alternative diagnosis should be considered.18
Table 1: Clinical score for the diagnosis of gout, adapted from Janssens et al (2010)
| Feature |
Clinical score |
| Serum urate > 0.35 mmol/L |
3.5 |
| Metatarsophalangeal joint involvement |
2.5 |
| Male sex |
2 |
| Previous reported flare |
2 |
| Hypertension or ≥ 1 cardiovascular disease* |
1.5 |
| Joint erythema |
1 |
| Onset within one day |
0.5 |
| Score |
Maximum 13 |
* Angina, myocardial infarction, heart failure, cerebrovascular event, transient ischaemic attack or peripheral vascular
disease
Septic arthritis should be considered in patients with monoarticular joint pain, with erythema, warmth
and joint immobility; systemic symptoms may also be present.20 Often the patient will have an underlying
condition affecting the joint, e.g. osteoarthritis, and concurrent treatment with an immunosuppressive medicine increases
the likelihood of infection.20 The knee is most often affected by septic arthritis, followed by the hip,
shoulder, ankle and wrist.20 Patients with septic arthritis will often have an elevated serum white blood
cell count and C-reactive protein levels may also be raised.20
Acute calcium pyrophosphate crystal arthritis, also known as calcium pyrophosphate deposition (CPPD) disease,
and previously known as pseudogout, is an arthritis caused by the accumulation of calcium pyrophosphate crystals.21 Acute
calcium pyrophosphate crystal arthritis has a prevalence of 4–7% in European populations;21 the prevalence
among Māori and Pacific peoples is unknown. Previous joint damage is a strong risk factor for calcium pyrophosphate crystal
arthritis and the condition becomes more likely if the first onset of symptoms occur later in life as it is rare in patients
aged under 60 years.21 Patients with calcium pyrophosphate crystal arthritis often have systemic symptoms,
including fever and chills, and elevated inflammatory markers, which can make it difficult to distinguish from infection.21 Where
there is clinical uncertainty, calcium pyrophosphate crystal arthritis can be differentiated from gout and septic arthritis
by requesting laboratory analysis of aspirated joint fluid.21 Radiography can also be used to support a diagnosis
of acute calcium pyrophosphate crystal arthritis in joints that are unable to be aspirated.21 Unlike gout,
calcium pyrophosphate-lowering medicines do not exist and treatment is focused on symptom relief.
Further information on diagnosing and managing calcium pyrophosphate crystal arthritis is available from:
www.bpac.org.nz/bpj/2013/october/cppd.aspx
Medicines for gout flares are determined by the patient’s characteristics
Patients with gout often initially present due to a flare, which will be the treatment priority. Patients should rest
and elevate the affected joint during a gout flare and some may find the use of a ice pack beneficial.1
A NSAID, corticosteroids or colchicine may be prescribed to treat gout flares
Options for the treatment of gout flares are:22, 23
- Naproxen 750 mg initially, 500 mg eight hours later, then 250 mg every eight hours until the flare has settled
- Prednisone 20 – 40 mg, once daily, for five days; tapering the dose over ten days can reduce the likelihood of a rebound
flare, but tapering is not always necessary
- Colchicine 1 mg immediately , followed by 500 micrograms after one hour on day one, and then twice daily dosing of
500 micrograms* 22
- Triamcinolone acetonide intra-articular injection , 2.5 – 40 mg, determined by the size of the affected joint
* This is an alternative dose to the traditional regimen, which is now recommended by many experts.
In patients with an estimated glomerular filtration rate (eGFR) < 50 mL/minute/1.73m2 the initial
dose should not exceed 1 mg in the first 24 hours, with a total maximum of 3 mg over four days
There is insufficient evidence to directly compare the efficacy of medicines for the treatment of gout flares.22 Medicine
selection is therefore based on the patient’s preference, renal function, the presence of co-morbidities, e.g. prednisone
may be preferred over a NSAID or colchicine in a patient with reduced renal function, and the concurrent use of medicines
that may interact with colchicine (see: “Particular care is required with colchicine”).
If a patient is experiencing severe flares of gout, e.g. involving multiple joints, it may be appropriate to prescribe
combination treatment, e.g. a NSAID with colchicine or corticosteroids with colchicine.22
Provide a “pill in the pocket” for managing future flares
Patients with gout require ready access to medicines for managing flares until they achieve long-term symptom control
with urate-lowering treatment. It is often necessary to prescribe an extra quantity of medicine for this purpose; emphasise
to patients that they should stop taking the medicine when the flare has settled, unlike urate-lowering treatment which
should be taken every day. Medicines should be stored in a secure and safe location at work and at home. Special care
should be taken with colchicine as relatively small overdoses can be fatal. Patients should take medicines promptly for
acute flares and those taking colchicine should do so within 12 hours of flare onset.22
Particular care is required with colchicine
Colchicine has a narrow therapeutic index meaning that the range between therapeutic and toxic effects is small, and
can overlap. Serious adverse effects associated with colchicine include paralytic ileus, myopathy, myocardial toxicity
and blood dyscrasias. Colchicine is contraindicated in patients with significant gastrointestinal or cardiac conditions
or pre-existing blood dyscrasias.24 The adverse effects of colchicine may also be exacerbated by medicine
interactions.24 Caution is advised when prescribing colchicine to patients who are taking medicines that
inhibit the CYP 3A4 enzyme and/or p-glycoprotein, e.g. erythromycin, clarithromycin and verapamil.1 There
have also been reports of myopathy and rhabdomyolysis in patients taking colchicine with statins.1 Colchicine
is very toxic in overdose and there is no reversal agent; deaths have occurred with accidental overdose as low as 6–7mg.
Prescribe the lowest effective dose of colchicine for the patient, and provide clear instructions on how and when to
take it. Patients should be advised to stop taking colchicine and seek medical attention if they experience nausea, vomiting,
diarrhoea or abdominal pain.24
Further information is available from:
www.bpac.org.nz/bpj/2014/september/safer-prescribing.aspx
The NZF interactions checker provides details on medicine interactions and their clinical significance,
available from: www.nzf.org.nz
Talk about urate-lowering treatment before the patient leaves
Urate-lowering treatment should be discussed with all patients with gout once a diagnosis has been established.22 This
includes patients who are currently experiencing a gout flare, as they should be provided with the opportunity to manage
their gout immediately, and some may not return for a follow-up consultation once the pain of the flare has resolved.
The discussion should also cover the importance of titrating the dose of urate-lowering treatment over time for it to
be effective.
Aim to initiate urate-lowering treatment early
Patients with hyperuricaemia and the following characteristics should start urate-lowering treatment:1, 22
- Two or more flares per year
- Tophi or erosions on X-ray
- Renal impairment
- Kidney stones
If the patient is presenting for the first time with a gout flare, ask about any prior episodes that they may have treated
themselves that are likely to have been gout; frequency and severity of gout can often be underestimated and therefore
under-treated. A recently published randomised controlled trial has demonstrated that urate-lowering treatment in patients
with early gout (with one or two prior flares) resulted in reduced incidence of gout flares and improved MRI-determined
synovitis.25 Patients who are initiated on urate-lowering treatment are less likely to require treatment
for gout flares and are therefore less likely to experience adverse effects from repeated exposure to NSAIDs.
Practice changing point: urate-lowering treatment can be initiated during a flare
Traditionally, initiation of urate-lowering treatment has been delayed until the pain of a flare has resolved. The rationale
being that dispersion of urate crystals during the initiation phase of treatment may make the patient’s pain worse. However,
there is little evidence to support this delay and two randomised controlled trials have found no increase in pain, flares
or markers of inflammation when allopurinol was initiated during a flare, compared to waiting ten days.26, 27
Best practice tip: If allopurinol is initiated during a flare, start at a low dose and ensure that the
patient understands that they need to continue allopurinol after the flare has resolved, even when other medicines for
treating the flare are ceased. In some cases medicines used for the treatment of gout flares will be continued at lower
doses for flare prophylaxis.
Adherence is the key to long-term management
Explain to patients that adherence to urate-lowering medicines needs to be life-long to prevent flares of gout from
returning. If initiation of urate-lowering treatment has been delayed until after a flare has been resolved, ensure that
patients know that they should continue urate-lowering treatment during any future flares. If urate-lowering treatment
is stopped, even after years of being symptom-free, most patients will experience a return of flares within four years.28
Rongoā rākau does not interfere with conventional gout treatments
Rongoā rākau (traditional plant remedies with healing properties) may be used by some Māori patients to treat flares
of gout.4 This may be in the form of a poultice or plant material added to bathwater. Urate-lowering medicines
can be used safely in combination with Rongoā rākau and should not be discouraged. Positive discussions about traditional
medicines are helpful as they break down barriers with patients and allow prescribers to assess if any interactions
with conventional medicines are likely.
Keep reading: Part 2: Controlling gout with long-term medicines.