Summary

Objective: To review the current management of gout in primary care with particular attention to lifestyle advice and drug management.

Design: A retrospective non-interventional study of gout management.

Subjects: Patients attending the Family Medicine Training Centre (FMTC) of the Prince of Wales Hospital between 1st July 2003 to 30th September 2003 with the diagnosis of gout.

Main outcome measures: Baseline demographic data, frequency and quality of lifestyle advice given, serum urate levels and type of antihyperuricaemic drug used.

Results: 279 patients were identified in the study. 53% were given lifestyle advice. Amongst the 67% patients given medications for acute gout control: 52% had NSAIDs alone for acute attacks, 29% colchicine alone, and 19% both colchicine and NSAIDs. 70% of patients were given allopurinol as antihyperuricaemic agent. None of our patients was prescribed uricosurics. 34% had no obvious cause for the use of allopurinol. 19% had multiple indications, the commonest being hyperuricaemia (49%). The majority of those on allopurinol had urate levels of more than 0.36mmol/L. Different allopurinol doses had no different effect on urate levels.

Conclusion: The current management of gout in terms of lifestyle advice and drug treatment for acute and chronic gout varied widely within our FMTC. Areas for improvement include the appropriate use of medications in the acute attack, the appropriate initiation of antihyperuricaemic agent, and the quality of message given in terms of lifestyle modification. Further auditing in gout management and the development of guidelines will provide additional benefits to our patients.

Keywords: Gout, hyperuricaemia, urate, allopurinol

摘要

目的：回顧目前基層醫療痛風的治療，特別是提供改善生活方式建議和用藥的情況。

設計：痛風治療的回顧性非干預性研究。

對象：在2003年7月1日至2003年9月30日到威爾斯親王醫院家庭醫學培訓中心就診的痛風病人。

測量內容：人口統計學基本資料；所提供的生活方式建議的次數和質量；血清尿酸鹽水平和抗高尿酸血症藥物的種類。

結果：共對279 病人進行了研究。53%的病人得到了生活方式建議。用藥物治療急性痛風的病人佔 67%，其中：52%的人預防性地使用非類固醇消炎止痛，29%的人使用秋水仙；F19%的人二者並用。70%的病人使用別嘌吟醇作為抗高尿酸血症藥物。沒有人使用促尿酸尿藥物。34%使用別嘌吟醇的病人沒有明確的原因；19%的病人有多種指徵，最常見的原因為高尿酸血症（49%），大多數使用別嘌吟醇病人的血尿酸值超過0.36mmol/L。別嘌吟醇的劑量不同對尿酸水平沒有影響。

結論：目前家庭醫學培訓中心，痛風的治療在生活方式建議和急、慢性痛風的藥物治療方面，都有很大差異。急性發作時如藥物的使用，如何啟用抗尿酸血症藥物和改善生活方式之建議的質量等方面都需加以改進。對痛風療法進一步進行審核和制定有關痛風治療的指引，可以為病人健康帶來更多益處。

主要詞彙：痛風，高尿酸血症，尿酸，別嘌吟醇

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Introduction

Gout (monosodium urate crystal deposition disease) is not an uncommon problem in Hong Kong, with a prevalence of 5-6% in the latest population statistics.¹ All patients with gout may have hyperuricaemia at some point in their disease. However, most of the hyperuricaemic individuals never experience a clinical event resulting from urate crystal deposition.

Gout progresses in four stages:

1. Asymptomatic hyperuricaemia - does not require treatment
2. Acute gout
3. Intercritical gout
4. Chronic tophaceous gout - tophi usually develop 10 years or more after the onset of gout, and can resolve after 6-12 months of normouricaemia²

After one gouty attack, a patient may never have another, or they may have a recurrence 3-42 years later (mean 11.4 years).³ In the Framingham study, one quarter of patients with acute gouty arthritis had only one attack in the 12 years of follow up.⁴

The management of acute gout is aimed at prompt reduction of inflammation and pain. The affected areas are exquisitely sensitive to even minor stimuli and should be protected from trauma. Acute gout responds quickly to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or colchicine.^5,6 Resolution occurs over several weeks without any treatment. NSAIDs are used as the first-line medication because of their relatively low side-effect profiles. The use of colchicine should be reserved for those intolerant of NSAIDs or those who have used this agent with success in the past, since colchicine is associated with more frequent adverse reactions and unpredictable effects.⁷ The concomitant use of NSAIDs and colchicine has not been recommended.

The long-term management of gout involves treating hyperuricaemia through risk modification and drug therapy. Secondary prevention should focus on changing hyperuricaemia-promoting factors, such as diet, alcohol intake,⁸ hypertension, obesity,⁹ thiazide diuretic therapy,¹⁰ and water consumption. Although a severely purine-restricted diet may reduce urinary uric acid excretion by 200 to 400mg/day, mean serum urate concentration decreases only about 1mg/dL (0.059mmol/L). Such restricted diets are unpalatable and are often neither practical nor effective in the management of hyperuricaemia and gout in patients with a previously normal dietary habit. However, it is worth noting that the avoidance of specific components, such as organ-rich foods (e.g. liver, sweetbreads), beer, or distilled spirits (which enhance serum urate levels) would be beneficial, especially in those taking a typical Chinese diet.

Since antihyperuricaemic drugs are prescribed for an indefinite and possibly life-long period, the indications for reduction of serum urate levels should be carefully considered before drug treatment is initiated.^11-13 Treatment for hyperuricaemia should be initiated in patients with:

• Frequent and disabling gouty attacks
• Chronic gouty joint disease
• Presence of tophi
• Gout with renal insufficiency
• Recurrent nephrolithiasis
• Persistent excessively elevated blood urate levels (0.773mmol/L in men, 0.595mmol/L in women)
• Urinary urate excretion <6.5mmol daily
• Cytotoxic chemotherapy or radiotherapy for lymphoma or leukaemia

The general goal of treatment is to achieve a serum urate concentration of 0.30 to 0.36mmol/L, a level substantially below that at which monosodium urate is saturated in extracellular fluids.¹⁴ Reduction of serum urate levels to <0.36mmol/L generally reduces the recurrence of gouty arthritis, but levels of <0.30mmol/L may be necessary for tophi resorption.¹⁵ There are two choices of therapy for lowering blood urate levels: allopurinol and uricosuric drugs. There is some controversy in determining treatment for each individual patient. The need to measure 24-hour urinary uric acid levels, allowing determination of whether a patient's hyperuricaemia is caused by urate overproduction or decreased excretion, has been debated. The proponents of this evaluation state that an over-producer should be treated with allopurinol while an under-excreter should be prescribed an uricosuric agent.¹⁶

Gout management, therefore, is not simple. Because of the large number of variables, management of acute and chronic gout also widely differs amongst different clinics and individuals. This study aims to review the management habits of gout in the primary care setting, with a view to standardising and improving patient care.

Methods

This was a retrospective study looking at case notes of patients who had attended the Family Medicine Training Centre (Prince of Wales Hospital, Shatin, Hong Kong) during the period from 1st July 2003 to 30th September 2003 for follow up of gout (International Classification of Primary Care T92). The diagnosis of gout had been determined clinically. Information starting from the first consultation (dating back to 1999 - year of clinic set-up) for gout at our clinic was gathered including:

1. Age
2. Gender
3. Drug usage for gout (all stages)
4. Indications for allopurinol use
5. Documentation of lifestyle advice (e.g. low purine diet, decrease alcohol use)
6. Serum urate levels

Patients who were new to the clinic over the three-month data collection period and those who were not attending our clinic for gout were excluded from the review. Serum urate levels were further correlated with other variables collected above. In particular urate levels in those taking different doses of antihyperuricaemic drugs were further analysed, with their confidence intervals calculated through standard statistical methods.

Results

279 cases of gout were identified during the three-month data collection period. Thirty were excluded (six of these were not followed up at our clinic and 24 were new cases). The collected data are shown below.

The majority of cases were males and elderly patients, the highest prevalence being in the 70-79 years age group. (Table 1and Figure 1).

On the whole, 53% (132/249) were noted to have been given lifestyle advice, mostly in the form of "advice on low purine diet" (Figure 2). In the group without any drug prescription, 44% (15/34) were given lifestyle advice.

Figure 3 shows the use of medications in our group of patients. 215 patients were given some form of medications for gout treatment. 57% (122/215) were given medications for acute gout control, while 175 cases 81% (175/215) were given allopurinol as urate lowering therapy. None of our patients was prescribed uricosuric drugs. Amongst those given medications for acute gout control, 52% (64/122) were given NSAIDs alone, 29% (35/122) were given colchicine alone, while 19% (23/122) were given both colchicine and NSAIDs.

Figure 4 shows the indications for allopurinol use. 34% (60/175) had no obvious cause, as shown from our computer records. Indications identified in order of decreasing frequency were: hyperuricaemia [49% (85/175)] (defined as urate >0.37mmol/L in females, >0.43mmol/L in males), frequent attacks [33% (58/175)], nephropathy [8% (14/175)], nephrolithiasis [5% (8/175)] and tophaceous gout [0.5% (1/175)]. 27% (48/175) had multiple indications.

In those patients taking allopurinol, 14% (24/175) did not have any serum urate levels taken during their follow up at the FMTC (Figure 5). 17% (29/175) had levels of less than 0.36mmol/L, the majority being more than 0.36mmol/L.

Figure 6 shows the urate level amongst the subgroup of patients who has had urate levels taken. Cut-off points were set as 0.595mmol/L and 0.773mmol/L for female and male patients respectively (levels defined as excessively elevated). No male patients had an excessively elevated urate level. 13% of female patients (8/63) had levels greater than 0.595. Amongst these, only 25% (2/8) were prescribed allopurinol. Of the 55 female patients with urate <0.595, 73% (40/55) were on allopurinol. Of the 145 male patients, 75% (109/145) were on allopurinol.

The average urate levels for those taking allopurinol were 0.458mmol/L (95% CI 0.02) at 100mg daily, 0.449mmol/L (95% CI 0.03) at 200mg daily, and 0.455mmol/L (95% CI 0.05) at 300mg daily (Figure 7).

Discussion

Study population

Although it is stated in textbooks that gout is more common amongst male patients, female patients in this study also comprise a significant proportion (male to female ratio around 2:1). This may reflect the true population gender distribution, though one cannot rule out diagnostic errors and selection bias.

Non-pharmacological management

For most of the patients with hyperuricaemia alone, drug treatment may not be needed. However, patient education into various lifestyle modifications would be important as a long-term strategy in those with and without drug treatment. In our study population, we observed that a large proportion of patients (117/249, 45%) did not have any written evidence for lifestyle advice. This may either reflect that no advice had been given, or that this information had simply not been written down in the notes. The quality of information given to patients, as evident from their medical records, also varied including "advised on low purine diet", "advised to cut down on alcohol", or "advised on a healthy lifestyle". The details of these statements and how much of these were understood by patients would be difficult to assess unless further qualitative studies are performed.

Pharmacological management - acute and prophylaxis

NSAIDs were more commonly used than colchicine in the prophylactic or acute management of gout. A significant number [19% (23/122)] were given both medications, a method that has not been recommended. As discussed above, NSAIDs are the drug of choice because of their relatively low side-effect profile as compared to colchicine. The combination of both medications will simply increase the number of adverse events without giving any additional benefits.

Pharmacological management - antihyperuricaemic therapy

Indications for starting antihyperuricaemic therapy have been well established. In this study allopurinol was the only drug prescribed for this purpose. However, 34% (60/175) had no obvious indication for this. Although none of our patients reported side-effects from long-term allopurinol treatment, potential harms from such therapy must be considered.

Hyperuricaemia (defined as urate >0.37mmol/L in females, >0.43mmol/L in males) was the commonest reason for allopurinol prescription. Only a small minority (8 out of 208 patients) had an excessively raised urate level requiring the use of antihyperuricaemic therapy. However, amongst these eight patients, only two were given antihyperuricaemic therapy. Allopurinol is not without side-effects, most common being skin rash and gastrointestinal disturbances. Hepatotoxicity and blood disorders have also been reported, though these are rare. Therefore the justification for initiation of allopurinol in those with a mildly elevated serum urate should be reconsidered unless there are other indications.

More importantly, in the majority of cases, the use of allopurinol therapy did not decrease serum urate to the target level of 0.36mmol/L. In addition, there were no significant differences in urate levels between different allopurinol dosages. Drug compliance to allopurinol is one of the reasons that need to be considered. Differences between an over-producer and an under-excretor may also need to be taken into account. It may be more appropriate if prior investigations and subsequent uricosuric prescriptions are used, especially for non-responsive cases to allopurinol and under-excretors.

Limitation

This study was carried in the Family Medicine Training Centre within a hospital setting. This is not typical of patients in the primary care setting, where many patients would have been newly diagnosed with gout rather than referred for continuation of treatment. In particular some of our patients may have had higher urate levels when gout was first diagnosed. It will be more informative if their initial presentations, initial urate levels and indications for starting antihyperuricaemic therapy could be determined by tracing their old written case notes.

As this was not a controlled trial, patient compliance could not be accounted for, and this may have an effect on the lack of response to different doses of allopurinol therapy.

Finally, it was not possible to assess patients' demands which would have influenced drug prescription.

Suggested areas of improvements for future gout management

The main areas for improvement required as a result of this study are the following:

1.	Emphasis on non-pharmacological aspect in gout management
	-	better notes keeping and documentation on lifestyle management.
	-	use of patient information leaflets to allow better patient education and patient empowerment.
	-	patient counselling by clinic nurses should be reinforced.
2.	Appropriate use of NSAIDs and colchicine
	-	use of NSAIDs as first-line in the treatment of acute gout.
	-	colchicine as a second-line treatment if NSAIDs are contraindicated.
	-	withhold from the concomitant use of NSAIDs and colchicines.
3.	Appropriate use of antihyperuricaemic drugs
	-	fulfilment of criteria prior to initiation of antihyperuricaemic drugs.
	-	need for serum urate level monitoring to ensure adequacy of treatment.
	-	consider changing to another class of antihyperuricaemic drug if urate level is not adequately lowered.
	-	consider checking urinary urate excretion in cases not responsive to allopurinol.
Implementing these aspects in our future care with completion of the audit cycle at a later stage will help to see whether such changes will improve the care of patients with gout.

Key messages

1. The prevalence of gout in Hong Kong is around 5-6%.
2. In the Framingham study, one quarter of patients with acute gouty arthritis had only one attack in the 12 years of follow up.
3. The long-term management of gout involves treating hyperuricemia through risk modification and drug therapy.
4. In our review, the management of gout in terms of lifestyle advice and drug treatment varied widely. The commonest reason for starting antihyperuricaemic therapy in our review was hyperuricemia. 24% had no obvious cause for such therapy.
5. Further auditing and guidelines development will enable better gout management for our patients.

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References