Younger age of onset of gout in Taiwan

K.-H. Yu and S.-F. Luo

Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Republic of China


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Objective. To study the clinical features of gout in the community and in medical centres, and to describe the recent changes in gout in Chinese patients.

Methods. We analysed retrospectively the clinical features of 1079 Chinese gout patients seen by a rheumatologist between 1993 and 2000. These included 558 patients from a private clinic and 521 patients from a medical centre. The data were compared with those in previous reports of large Caucasian and non-Caucasian series.

Results. The mean age of onset was 41.6 yr and the mean disease duration before first visit was 4.2 yr. For medical centre patients, the mean age of onset was 43.0 yr and mean disease duration before the first visit was 4.8 yr. For private clinic patients, the mean age of onset was 40.2 yr and mean disease duration before the first visit was 3.6 yr. Young patients with gout, with onset before age 30, constituted 23.3 and 26.7% of the medical centre and private clinic patients respectively. Female patients constituted 10.6 and 5.6% respectively, the family history was positive in 27.1 and 28.7%, and urolithiasis occurred in 11.5 and 10.9%. Tophi were found in 21.1% of medical centre and 12.7% of private clinic patients. The mean time from first gouty attack to visible tophi was 6.6 yr in those who developed tophi.

Conclusions. The age at onset of gout was much earlier than in previous reports. Twenty-five per cent of patients had their first gouty attack before age 30. The first attack frequently occurred between the third and fifth decades (68.2%) rather than between the fourth and sixth decades, as reported in previous papers. The incidence of gout in females had increased (8.0% of the patients were female) and the incidence of tophi was high (16.8%). Besides, our patients had more frequent gouty attacks and the interval from the first attack to visible tophi was shorter than in previous reports of the disease in Caucasians.

KEY WORDS: Gout, Tophi, Clinical features, Chinese, Community, Medical centre.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Gout is a disease of purine metabolism with a prevalence of 0.2–0.4% and an annual incidence of about 0.010–0.015% [16]. In previous reports, the first gouty attack usually occurred between the fourth and sixth decades and onset before age 30 yr was considered to be rare [7, 8]. However, in the past 15 yr we have found more patients with younger age of onset than in the previous reports, and that the percentage of chronic tophaceous gout was still high and the interval to tophus formation was much shorter [9]. Previous clinical reports of large series of patients with gout were almost all from medical centres and did not include community studies. There were some epidemiological studies of the community, but these focused primarily on hyperuricaemia and included few cases of gout [1, 2]. We therefore performed a clinical analysis that included gout patients from a private clinic and a medical centre.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
We analysed retrospectively the clinical features of 1079 Chinese gout patients who first visited our clinic between 1993 and 2000. All fulfilled the 1977 American Rheumatism Association criteria for acute gout [10]. They included 558 private clinic and 521 medical centre patients seen by a senior rheumatologist (KHY). In Taiwan, the government has implemented a national health insurance programme, which covers the health-care of over 97% of the population. Patients can obtain medical service from any private clinic or medical centre of their own preference, which does not necessarily require referral. The 558 private clinic patients came from a daily general practice in Tao-Yuan City in northern Taiwan. In this private clinic, 20 141 patients were seen between 1993 and 2000, including 13 970 adults and 6171 children. Gout patients constituted 2.8% of the total number of patients; this figure is similar to those found in the Framingham study (1.5%) [1] and the Normative Aging Study (4.1%) [2]. The 521 hospital patients were seen in the Rheumatology Clinic of Chang Gung Memorial Hospital, where one of the authors (GHY) attended the Rheumatology Clinic once weekly. Chang Gung Memorial Hospital, Lin-Kou, Tao-Yuan, is the largest medical centre in Taiwan; it provides a medical service to people island-wide and receives about 5% of the National Health Insurance payment per year. There were, on average, one or two new gout patients every clinical session. In total there were about 4500 new out-patients with rheumatic complaints seen during this period. Gout constituted about 11.6% of new patients and one-quarter of the total number of patients per clinic. This proportion also represents an average figure, as in other rheumatology staff clinics, and is similar to the report of 23% gout patients in the rheumatology clinic of another teaching hospital in southern Taiwan [11].

Clinical features, including sex, age of onset, time to first visit, family history, urolithiasis history and tophi, were analysed. Serum urate, creatinine and 24 h urinary uric acid excretion were also analysed if available. Serum creatinine and urate concentrations were determined with a Hitachi 7450 autoanalyser (Hitachi, Tokyo, Japan), using the Jaffe method for creatinine and the uricase differential spectrophotometric method for uric acid. Clinical features of gout in Chinese patients were compared with those described in previous reports of large Caucasian and non-Caucasian series of gout patients.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Age of onset and the time to first visit
For medical centre patients, the mean age (±S.D.) of onset was 43.0±15.4 and mean disease duration before first visit was 4.8±5.3 yr. For private clinic patients, the mean age of onset was 40.2±13.9 yr and mean disease duration before first visit was 3.6±3.8 yr. Female patients constituted 10.6 and 5.6% respectively. Overall, the mean age of onset was 41.6±14.7 yr and mean disease duration before the first visit was 4.2±4.6 yr (Table 1Go). Females constituted 8.0% of patients, and 74% of them were over age 50 yr. The mean age of onset (41.6 yr) was much younger than in our previous report (47.8 yr) in 1993 [12] and reports on Japanese patients [13] and from the Framingham study [1] (49.5 and 48.7 yr respectively). In the medical centre and private clinic patients, patients with gout with onset before age 30 yr constituted 23.3 and 26.7% of the patients respectively. The first attack of gouty arthritis usually occurred between the third and fifth decades rather than between the fourth and sixth decades reported previously. Twenty-five per cent of patients had their first gouty attack before the age of 30 yr (Table 2Go).


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TABLE 1. Clinical features of 1079 gout patients (1993–2000) compared with data before 1993

 

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TABLE 2. Age of onset of gouty arthritis compared with data before 1993

 

Frequency of gouty attack
The frequency of gouty attack varied in different individuals and in different periods in the same individual. The percentage of patients having more than five attacks per year in our study (Table 3Go) was 36.2%, which is more frequent than reported in the Framingham study (23%) [1] and Yu's series (23%) [14].


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TABLE 3. Frequency of gouty attack

 

Family history
The family history was positive in 27.1% of medical centre and 28.7% of private clinic patients. This is similar to the 30% reported in Yu's series [14]. It is noted that the younger the age of onset, the higher was the percentage of positive family history (Table 4Go).


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TABLE 4. Relationship between family history and age of onset of gout

 

Laboratory data
The percentage of patients who were normouricaemic during gouty attack was 28.8, but the follow-up urate level was usually more than 9.0 mg/dl. Mean serum urate concentration was 10.3 mg/dl (Table 1Go). This finding is similar to that reported for gout in Japanese patients (10.1 mg/dl) [13]. There was 15.7% overproduction (daily uric acid excretion more than 800 mg), which is similar to our previous data in 1993 [14] (17.8%) but is lower than Yu's report (24.2%) [12].

Urolithiasis
There was a history of urolithiasis for 11.5% of medical centre patients and 10.9% of private clinic patients (Table 1Go). This is lower than in Yu's series [14] (26.0%) (Table 5Go). The difference is probably due to a longer period of observation in Yu's series and less uricosuric agent-related urolithiasis in our patients. Another explanation is that the prevalence of urolithiasis in gout is decreasing. The urolithiasis had developed before first gouty attack in about 56% of our patients.


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TABLE 5. Comparison of the clinical features of gout between large series

 

Tophi
Tophi were found in 21.1% of the medical centre patients, which is similar to our report (24.8%) in 1993 [12]. In private clinic patients, there were only 12.7% with tophi (Table 1Go). However, this percentage is still higher than those for other hospital series from Japan [13] and the Mayo Clinic [15]. Excluding those who could not remember the time of tophus formation, the interval from first gouty attack to visible tophi was 7.0±3.7 yr in medical centre cases and 5.9±3.9 yr in private clinic patients. In total, 16.8% of our gout patients had tophi, and the mean interval from first gouty attack to visible tophi was 6.6±3.8 yr.


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
It has been reported that gout is on the increase in New Zealand [16]. Gout was supposedly rare in Taiwan in the decades before the 1960s [17, 18], but there has recently been a surprising increase in the number of gout patients in Taiwan [19]. In the 1960s, gout was found in only 61 out of 1200 patients with rheumatic diseases at a teaching hospital in Taiwan [20]. In the present study there were many more gout patients in Taiwan, both in the private clinics and medical centres. In previous reports, fewer than 10% of gout patients had disease onset before age 30 yr, which raises the suspicion of an unusual form of gout. The mean age of onset has been reported to be around 49 yr in both Caucasians [1] and non-Caucasians [13]. The present study is the first report of up to 25% of gout patients with onset before age 30 yr. The mean age of onset has got younger (41.6 yr) in comparison with our previous report in 1993 [12], in which the mean age of onset was 47.8 yr and only 11% of patients had disease onset before 30 yr of age (Table 5Go). The trend to a younger age at onset of gout in Taiwan is obvious, and the first attack usually occurred between the third and fifth decades rather than between the fourth and sixth decades reported previously (Table 2Go).

In a recent epidemiological study from Kinmen, Taiwan, the mean serum urate level in man was reported to be 6.14±1.43 mg/dl [21]. This is higher than in the Framingham study (5.12±1.11 mg/dl) [1], the Tecumseh study (4.90±1.40 mg/dl) [22] and data from Taiwan on Chinese patients (4.99±0.91 mg/dl) [23] in the 1960s. The prevalence of hyperuricaemia is 17.3% from Kinmen and the prevalence of gout is 1.3% in those aged more than 30 yr [21]. This prevalence is higher than in one previous epidemiological study in Taiwan [6], in which the prevalence of gout in rural, suburban and urban areas was 0.16, 0.67 and 0.67% respectively. Causes for the rising serum urate level and prevalence of gout are multiple, and include race, a westernized diet, alcohol consumption and environmental factors [2427]. Diuretic-induced gout was found in only three cases in the present study. Lead poisoning was previously an important cause of gout and there is one report of an elevated lead burden in gout patients in Taiwan [28]. However, it is uncommon nowadays and was not found in our patients. Excessive alcohol consumption, particularly if occasional, was indicated as the most important factor in the development of gout among asymptomatic hyperuricaemic men [25]. However, another community-based epidemiological study [24] of hyperuricaemia concluded that the hyperuricaemia was correlated with blood pressure, creatinine, triglyceride and offal consumption, but not with alcohol intake. A more recent study from the Nutritional and Health Survey in Taiwan [29] found a high prevalence of hyperuricaemia despite a lack of both obesity and high alcohol consumption. They suggested that a genetic component and other environmental factors might have important roles. This needs further study.

In two large population studies (the Framingham study and the Normative Aging Study), the prevalence of gout was initially 0.2 and 0.48% respectively, which had increased to 1.5 and 4.1% 14 yr later [1, 2]. In these reports, gout was mild. Only 8% of patients had tophi in the Framingham study and gouty attacks were rare. In contrast, the Gutman series [30] was the only one that emphasized the pretreatment clinical data. They found severe gout and 44% of the patients developed tophi. In the continued series of Gutman, there were still 34% of tophi, as reported by Yu in 1974 [31]. Our previous hospital data showing 24.8% of patients with tophi [12] support the observations of Gutman and of Yu. In the present study, there were 21.1% of hospital patients and 12.7% of community patients with tophi. Besides, we found more frequent gouty attacks. The percentage of patients having more than five attacks per year was 36%, compared with the 23% in the Framingham study and in Yu's series [14]. The interval to visible tophi has shortened considerably. Hench [32] reported in 1936 that the interval from the first attack to the beginning of chronic arthritis or visible tophi was 3–42 yr, with an average of 11.6 yr. In our study, tophi developed from 1 to 18 yr with a mean of 6.6 yr after the first gouty attack.

Gout was rare before World War II and has been increasing since that time. The low incidence of gout before 1940 may be due as much to diagnostic classification as to actual existence of the disease. The natural course of gout has not been well clarified because only one report mentions the situation in the pretreatment era—that of Gutman [30]. According to this report, 30% of patients would have demonstrable tophi 5 yr after diagnosis of gout, increasing to 50% by 10 yr and 72% by 20 yr. Other reports on the clinical features of gout vary widely. All these reports include only hospital cases, and most patients were treated [1315]. There is no large-series community-based report on the clinical features of gout in the literature. Our present study included both medical centre and community gout patients in Taiwan, and showed an increased incidence and younger age of onset of gout, increased severity with more frequent attacks, a high incidence of tophi and a shortened interval to tophus development. We emphasize that early treatment of gout by diet control and anti-hyperuricaemic medication is important to reduce the attack frequency and prevent the formation of tophi.


    Notes
 
Correspondence to: S.-F. Luo, Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China. E-mail: gout{at}adm.cgmh.org.tw Back


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Submitted 28 December 2001; Accepted 28 May 2002