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Dr Nicola Dalbeth, Rheumatologist and Senior Lecturer, Department of Medicine, University of Auckland
- Gout is a major cause of arthritis in New Zealand, with high rates of severe disease in Māori and Pacific patients
- Gout causes significant disability in Māori and Pacific men of working age
- All patients with gout should have cardiovascular disease (CVD) risk assessment, and intensive management of modifiable
- Long-term preventive therapy with allopurinol is critical for effective gout management:
- Prescribe early, before development of tophi
- Monitor serum uric acid levels
- Aim for target serum uric acid <0.36 mmol/L
- Introduce gradually: ‘start low and go slow’
- Use colchicine prophylaxis
- Minimise diuretic therapy in patients with gout
What is gout
Gout is an arthritis caused by the inflammatory response to intra-articular monosodium urate crystals. Supersaturation
of urate typically occurs in physiological fluids above concentrations of 0.42 mmol/L. In early disease, gout presents
as recurrent episodes of self-limiting acute inflammatory attacks (‘flares’) of arthritis. These attacks most often affect
the 1st metatarsophalangeal joint, midfoot and ankle. In the presence of prolonged hyperuricaemia, some patients develop
recurrent polyarticular attacks, chronic tophaceous disease, erosive arthritis and renal disease (urate nephropathy and
uric acid stones).
Figure 1: An ulcerated tophus of gout (Courtesy of Dr Peter Gow)
Figure 2: Erosive gout
Natural History of Gout
If untreated, the evolution of gout follows four stages:
- Asymptomatic hyperuricaemia – asymptomatic hyperuricaemia has traditionally remained untreated with
drugs. Although evidence is building, linking hyperuricaemia with cardiovascular and renal disease, treatment remains
unproven. Identification of hyperuricaemia presents an opportunity to suggest diet and lifestyle changes to patients
and also to look for possible underlying causes for the raised uric acid. Of those with hyperuricaemia, 20% will go on
to develop acute symptomatic gout.
- Acute attacks – typically the first attack involves one joint but it can also be polyarticular. Without
specific treatment, an attack of acute gout is likely to resolve within 7–10 days. In practice, the severe pain usually
forces patients to seek pharmacological relief.
- Intercritical gout – the length of time between attacks can vary widely. Some patients only ever
have one attack, but for the majority, a second attack will occur within a year. If the urate level remains high (>0.36
mmol/L) despite the patient being symptom free, there can be ongoing joint inflammation and hence joint damage and tophi
- Chronic tophaceous gout – tophi are firm white translucent nodules in connective tissue arising from
the deposition of urate crystals. They can take at least 10 years after the initial attack to develop. As well as causing
joint destruction, they are disfiguring and also cause physical hindrance. Tophi can become inflamed or infected and
can exude tophaceous material.
Diagnosis of gout
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of gout here
The diagnosis of gout can be made according to the American College of Rheumatology (ACR)/Wallace criteria1:
- The presence of characteristic urate crystals in the joint fluid,
- A tophus proved to contain urate crystals by chemical means or polarized light microscopy
Figure 3: Needle shaped MSU crystals identified within the joint. Viewed under polarizing light with
a red compensator.
- Six of the following 12 clinical criteria
- Maximum inflammation within the first day
- More than one attack of acute arthritis
- Monoarticular arthritis
- Redness observed over joints
- First metatarsophalangeal joint pain attack
- Unilateral metatarsophalangeal joint attack
- Unilateral tarsal joint attack
- Suspected tophus
- Asymmetric swelling within a joint on x-ray
- Subcortical cysts with no erosions on x-ray
- Negative bacterial culture of joint fluid
It is important to note that gout and sepsis can co-exist. The presence of urate crystals in synovial fluid does not
exclude a diagnosis of sepsis.2
Although hyperuricaemia is a key risk factor for gout, it is not sufficient to make the diagnosis of gout; only
20% of patients with hyperuricaemia will develop gout, and serum urate concentrations may be normal in patients
during an acute gout flare.3
Treatment of gout
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guide for Diagnosis and Treatment of gout here
Treatment of acute gout flares
NSAIDs: given at regular intervals until the severe pain abates, at which time the dose may be reduced (e.g. starting
with naproxen 500 mg bd or diclofenac 75 mg bd). Always watch for renal impairment, heart failure and peptic ulceration.
If patients are already taking low dose aspirin for cardiovascular risk reduction it should be continued.
Oral corticosteroids: in view of the toxicity of colchicine, corticosteroids may be preferred to treat acute gout in
patients in whom NSAIDs are contraindicated, provided sepsis has been excluded. The initial dose is 15–40 mg prednisone
daily, gradually reduced over 10 days. Intra-articular corticosteroids are useful if monoarthritis is present to reduce
risks of systemic therapy.
Allopurinol should not be started at the time of the attack
Colchicine: can be a useful adjunct to NSAIDs in resistant cases, particularly when tophi are present, as monotherapy
or to prevent flares when starting allopurinol.
Allopurinol: If a patient has been taking allopurinol regularly at the time of developing an acute attack it should
be continued at the same dose.
Risk factors for gout
The key risk factors for gout are
- Male sex
- Māori and Pacific ethnicity*
- Chronic renal impairment
- Diuretic use**
- Coronary heart disease
- High intake of meat, seafood and alcohol (particularly beer)
*Māori patients with normal uric acid levels have been shown to have a reduced
excretion of urate. This suggests an underlying renal mechanism.4
**Diuretic therapy is a risk factor for the development of hyperuricaemia and recurrent gout attacks. Diuretic therapy
should be minimised and avoided wherever possible.
Colchicine dosing for acute gout
Due to recent concerns about toxicity, colchicine is no longer considered first line treatment for acute gout. In addition
colchicine should be used at a lower dose than has been recommended in the past.
“...The recommended dose for colchicine in the treatment of acute gout is 1.0 mg stat, followed by 0.5 mg six hourly,
up to a maximum dose of 2.5 mg per 24 hours...”
New Zealand Rheumatology Association (NZRA), endorsed by Medsafe.5
(full statement available at
After the first 24 hours, the dose should be reduced to 0.5 mg one or two times daily, according to renal function.
Prescribed in this way colchicine is safe and effective. The risk of diarrhoea and other toxic effects is minimised. Many
patients report that one or two colchicine tablets taken within the first few hours of the onset of pain can avoid a major
Adverse effects with Colchicine
Colchicine has a narrow therapeutic margin and considerable variation in absorption between individuals. Toxic effects
include diarrhoea, nausea and vomiting, electrolyte imbalance, alopecia, haematological effects, pancreatitis, and
failure of kidneys, liver or respiratory system. High doses can be fatal.
Adverse effects with Allopurinol
The most common adverse effect is a rash (1−2%), which may be more common in patients with renal impairment.
hypersensitivity syndrome (AHS) is extremely rare but potentially fatal. It is characterised by fever, rash, eosinophilia,
hepatitis and renal failure. Adverse effects can occur at any dose.13
Indications for Uric acid lowering therapy6-8
All patients with any one of the following should receive long-term uric acid lowering therapy:
- Recurrent gout attacks (≥2 attacks/year)
- Gouty arthropathy
- Radiographic damage
- Early onset, family history and serum uric acid >0.60 mmol/L
It should be noted that although effective treatment of gout can lead to regression of tophi, management is far more
difficult once tophi develop, due to the high total body urate load.
Hitting the target in gout: aim for a serum uric acid concentration of <0.36 mmol/L
Several recent studies have emphasised the importance of excellent long-term control of serum uric acid in order to
suppress gout attacks and achieve regression of tophi. These studies have identified a serum uric acid level of <0.36
mmol/L as the target required for dissolution of monosodium urate crystals within the joints and subcutaneous tissues.
target has been endorsed in the recent European League Against Rheumatism (EULAR) guidelines for management of gout.
Reduction of the serum uric acid level requires both pharmacological and non-pharmacological management. Allopurinol
is the first choice urate-lowering drug unless there is a history of allopurinol allergy/intolerance.
Allopurinol prescribing: a how-to guide
- Wait for at least two weeks after an acute gout attack before starting allopurinol
- ‘Start low and go slow’. Start with allopurinol 100 mg daily, and increase by 100 mg every two weeks until the serum
uric acid level is <0.36 mmol/L. For most patients with normal renal function, a dose of 300 mg daily is needed to
achieve this target. Patients with renal impairment may require less allopurinol to achieve this target. Sudden changes
in the serum uric acid level are likely to precipitate gout attacks. Gradually increasing the dose of allopurinol is
less likely to trigger a gout attack
- Use prophylaxis against acute attacks. Prophylaxis with colchicine (0.5 mg daily to twice daily) or NSAIDs for the
first three months of starting allopurinol (or until serum uric acid <0.36 mmol/L) should be prescribed to reduce
the risk of gout attacks.14 Ensure the patient knows that in this situation the colchicine
is for gout prevention and the dose should not be altered without medical advice if an acute episode occurs.
- Monitor serum uric acid levels on a monthly basis while establishing allopurinol. Once serum uric acid is <0.36
mmol/L, monitor uric acid and renal function on a three-monthly basis.
- Allopurinol should be continued as life-long therapy for management of gout, except in the case of allopurinol intolerance.
Do not stop taking allopurinol during an acute attack of gout.
Other urate-lowering drugs
The uricosuric agent probenecid is an effective urate-lowering drug in patients with normal renal function and urate
under-excretion. This agent is particularly useful in combination with allopurinol if there is persistent hyperuricaemia
despite therapeutic doses of allopurinol, or in allopurinol intolerance.15 A typical dose
is 250 mg twice daily for two weeks, then 500 mg twice daily thereafter.
Probenecid is contraindicated in patients with a history of renal stones. Patients should be advised regarding the importance
of high fluid intake while taking probenecid, around eight glasses of water per day.
Cam Kyle and Stephen Du Toit
About one third of body urate comes from the diet, two thirds from endogenous tissue catabolism. Under excretion of
urate by the kidneys is the cause of high serum levels in over 80% of adult patients. Insulin resistance (metabolic syndrome)
is associated with increased urate resorption and higher serum urate levels.
About 20% of males have a serum urate above 0.42 mmol/L, but this has been chosen as the upper end of the male range
because at that level urate becomes supersaturated in body fluids at 37°C, resulting in increased crystal deposition
in tissues. Above this level the 5–year risk of gout rises fifty-fold from about 0.1% below 0.42 mmol/L to 5% above 0.54
mmol/L. Above 0.60 mmol/L the 5–year prevalence of gout is about 30%.
An upper limit of 0.36 mmol/L is used for women because their levels before menopause average 0.06 mmol/L lower than
men. After menopause, levels in women approach those in men and the risk of gout increases, being similar to men over
Serum urate is the most important predisposing risk factor for gout, but is not used alone to make the diagnosis. Most
patients with high urate levels do not develop gout and, conversely, serum urate may be normal, especially during acute
attacks. Visual identification of crystals from joint fluid or tophi is the gold standard.
For patients with clinical gout on long-term treatment, a target urate level of 0.36 mmol/L has been recommended by
some international bodies. The long-term risk of gout recurrence is much lower when levels are maintained below this
threshold and it also favours the slow dissolution of chronic tophi, being well below the solubility constant of urate.
D-News, Diagnostic Medlab, August 2007 Available from:
Weight management is the key component in dietary management of gout. A 5% loss in body weight leads to a 10% reduction
in serum uric acid level.16,17 Diets very low in purines are generally unpalatable and poorly
tolerated over time. Patients are more likely to accept advice to reduce purine-rich foods than to be told not to eat
them at all (Table 1). Patients should be encouraged to eat regular meals and to drink plenty of water.
Table 1. Dietary advice for patients with gout
|What to reduce in
|What to include in
*Studies suggest that Vitamin C might be beneficial in the prevention and management
or gout and other urate-related diseases.19
**Beer confers a larger risk than spirits. Moderate wine intake does not increase risk22
***Refer to Bandolier article, (page 33 BPJ printed version only or Bandolier 160,
|Red meat, shellfish, oily fish18
|Sugar and sugar-sweetened drinks20
||Low fat dairy products18,21
|**Alcohol, especially beer22
When to refer to a rheumatologist
Referral is appropriate when there is:
- Persistent hyperuricaemia or gout attacks despite maximum tolerated allopurinol treatment
- Doubt about the diagnosis
- Failure to achieve prompt resolution of acute attacks
- Development of progressive bone and joint damage on x-ray
Consider CVD risk and metabolic syndrome for every patient with gout
There is increasing recognition that asymptomatic hyperuricaemia is an independent risk factor for development of CVD.
there is no current evidence that treatment of asymptomatic hyperuricaemia reduces the risk of subsequent CVD events.
Re-analysis of the Multiple Risk Factor Intervention Trial (MRFIT) has addressed the association of acute myocardial
infarction (MI) in patients with gout. In this study, gout was associated with increased risk of acute MI (OR 1.3, p< 0.001),
even after adjusting for BMI and metabolic syndrome.26 In patients attending gout clinics
in Auckland, 59% are at high risk of CVD events (>15% in the next five years) based on Framingham risk tables.27
Recent analysis of the National Health and Nutrition Examination Survey (NHANES III) showed that gout is associated
with increased risk of metabolic syndrome (OR 3.4, p< 0.001).28 In patients attending
gout clinics in Auckland, 87% have metabolic syndrome (using the revised Adult Treatment Panel (ATPIII) definition).27
Pharmacists have a key role in the care of people with gout
If you identify a patient who is regularly purchasing over-the-counter (OTC) medications for the treatment
of gout, encourage them to consult their GP to discuss the use of uric acid lowering medication, for the prevention
of future attacks.
Pharmacists can make a difference by helping identify patients at high risk of gout who may benefit from prescription
medication. Gout in New Zealand is common and increasing, particularly amongst Māori and Pacific Islanders. It is
often poorly treated and is a major cause of significant disability. Early intervention is vital. Educating patients to
accept that OTC pain relievers will not stop joint damage and that they are only of limited benefit in an acute attack
may help persuade people to visit their GP. Many patients are not aware that gout can be prevented through the use of
allopurinol. Those who have had a second acute attack require GP assessment and likely use of allopurinol. Good treatment
of gout requires a team approach. Encouraging people who are in a high risk group to see their GP will help achieve effective
treatment of gout. These high risk patients may also benefit from cardiovascular risk factor assessment.
Prevalence and impact of gout
Māori and Pacific People over-represented in GOUT clinics
Gout is the most common form of inflammatory arthritis affecting men.29 Gout is uncommon
in pre-menopausal women. Most women with gout are post-menopausal and taking diuretics.
Gout is on the increase in New Zealand.30 Recent data from primary care in Auckland shows
that gout affects 14.9% Pacific men, 9.3% Māori men and 4.1% European men (Richard Hulme, East Tamaki Health Care, 2006).
The same data has shown that gout is more frequently diagnosed than Type II diabetes in Māori and Pacific Island men.
Gout is now the most frequent cause for new patient referral to the rheumatology outpatient clinic in South Auckland,
and accounts for more than 200 inpatient admissions to Middlemore Hospital each year.31 Māori
and Pacific patients with severe gout are over-represented within gout clinics in the Auckland area (Table 1).
Table 1. Percentage of Māori and Pacific Island people presenting to gout clinics in Counties Manukau DHB.
||% DHB population
||% presenting to
Māori and Pacific patients attending these rheumatology clinics have higher serum uric acid levels, more work disability
and lower levels of musculoskeletal function than European patients (N. Dalbeth, unpublished data).
Why is gout such a problem in Māori and Pacific communities?
A study of gout patients in South Auckland has revealed some key issues (personal communication, Dr K Lindsay, CMDHB).
- There is minimal knowledge about gout and the medications used in treatment.
- Amongst the Pacific Island community in particular, there is a normalisation of gout, a stoicism and tolerance of
- Often knowledge of gout is based on jokes about over-indulgence, old age or unhelpful myths.
- These beliefs contribute to denial and result in missed opportunities for early diagnosis.
- Families take up the burden of caring for gout patients and these patients rarely present to general practice.
- Typically patients will use pain relief but not preventative medications, with a resulting increase in the number
of joints involved, the size of tophi, the frequency of attacks and number of days off work. Without appropriate use
of allopurinol, their gout is progressive and becomes chronic.
We are grateful to Dr Peter Gow and Dr Doone Winnard for their review of this article.
- Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary
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- Zhang W, Doherty M, Pascual E, et al. EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of
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- Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study.
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- Gibson T, Waterworth R, Hatfield P, et al. Hyperuricaemia, gout and kidney function in New Zealand Māori men. Br
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- NZRA consensus statement available online at
- Mikuls TR, MacLean CH, Olivieri J, et al. Quality of care indicators for gout management. Arthritis Rheum 2004;50(3):937-43.
- Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part II: Management. Report of
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- Jones P. The modern management of gout. New Ethicals Journal 2001;4:29-31.
- Perez-Ruiz F, Calabozo M, Pijoan JI, et al. Effect of urate-lowering therapy on the velocity of size reduction of
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- Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent
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- Li-Yu J, Clayburne G, Sieck M, et al. Treatment of chronic gout. Can we determine when urate stores are depleted
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- Medsafe. Apo-allopurinol. Medsafe datasheets 2006.Available from
- Dalbeth N, Kumar S, Stamp L, Gow P. Dose adjustment of allopurinol according to creatinine clearance dose not provide
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- Borstad GC, Bryant LR, Abel MP, et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for
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- Reinders MK, van Roon EN, Houtman PM, et al. Biochemical effectiveness of allopurinol and allopurinol-probenecid
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- Krejs GJ. Metabolic benefits associated with sibutramine therapy. Int J Obes Relat Metab Disord 2002;26 Suppl 4:S34-7.
- Dessein PH, Shipton EA, Stanwix AE, et al. Beneficial effects of weight loss associated with moderate calorie/carbohydrate
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- Choi HK, Atkinson K, Karlson EW, et al. Purine-rich foods, dairy and protein intake, and the risk of gout in men.
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- Huang HY, Appel LJ, Choi MJ, et al. The effects of vitamin C supplementation on serum concentrations of uric acid:
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- Gao X, Qi L, Qiao N, Choi HK, et al. Intake of added sugar and sugar-sweetened drink and serum uric acid concentration
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