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Gout and hyperuricaemia
5 Gout and hyperuricaemia JOHN DARMAWAN S A M U E L K. L U T A L O
Nowadays in industrialized countries gout is perhaps treated with a certain degree of complacency. Recognized from ancient times, this articular scourge has relinquished its dominant place in medicine, partly through the recognition of early disease and the availability of safe, effective remedies. However, in some tropical developing populations, gout is a cause of increasing morbidity. Studies in these populations continue to provide tantalizing insights into the environmental and hereditary factors associated with hyperuricaemia and gout.
EPIDEMIOLOGY Caution should be exercised in the interpretation and comparison of point prevalence rates of gout in different populations, surveyed by various study designs, diagnosed by different criteria, influenced by diurnal and seasonal variations in serum urate concentration, and affected by inter-observer variation. In addition, small sample sizes do generate wide 95% confidence intervals, crystal identification in epidemiology surveys is practically impossible and cases of non-urate arthropathy may be included in such studies. Despite these drawbacks, available data point to some striking and real differences in the prevalence rates of gout (Table 1) and hyperuricaemia (Table 2) in various populations. Gout was not recorded in Polynesians of the South Pacific islands and New Zealand before 1914 (Wohlmann, 1914). Yet, nowadays, some of the highest rates of gout and hyperuricaemia in the world are to be found in these populations. The Maoris of New Zealand have a predisposition to hyperuricaemia and the overall frequency of gout in men, recorded at around 10% in studies in the 1960s (Prior et al, 1966) is still today at this level with around one in three males over the age of 40 years affected, i.e. more than eight times that of age counterparts in Europe and North America (Gibson et al, 1984) and New Zealanders of European stock (Lennane et al, 1960). Elsewhere in the Pacific Island of Nauru 64% of men and 60% of women aged 20 years and over have hyperuricaemia, the highest prevalence rates yet reported for any population (Zimmet et al, 1978). The prevalence BailliOre's Clinical Rheumatology--
Vol. 9, No. I, February1995 ISBN0-7020-1946-1
83 Copyright9 1995,by Bailli6reTindall All rights of reproductionin any formreserved
J. D A R M A W A N A N D S. K. L U T A L O
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J. DARMAWAN AND S. K. LUTALO
rate of gout in men is 7%. The authors suggest that the high prevalence of gout is related to environmental changes from the traditional island style of living to one of almost complete Westernization, a point dramatically reinforced in a 14 year incidence study of Tokelauans (Prior et al, 1987). From a base-line of around 20:1000, the prevalence rose to 51:1000 in migrated Tokelauan males (to New Zealand) compared to a slight fall to 15:1000 in non-migrated males over the same period. The relative risk of gout was nine times higher in the migrant Tokelauans, placing them in the same risk class as the New Zealand Maoris. Age-specific incidence studies also revealed that gout occurs at an earlier age in migrant men. These prevalence and incidence changes in clinical gout were matched by significantly higher serum uric acid concentrations in migrants compared with non-migrants. Kellgren (1964) has suggested that the indigenous Polynesian inhabitants of the Pacific basin form one large, potentially gouty family, an observation which may extend to the Malayo-Polynesians of Java. Darmawan et al (1992) have found rates of gout and hyperuricaemia in rural Javanese to be similar to that of non-migrant Tokelauans and higher than most Caucasian populations in the absence of alcohol consumption and a very low meat consumption. There was no association either with wealth, social class or body mass index. These observations imply that other, probably genetic, factors operate in these indigenous populations. In a study of Maori men, Gibson et al (1984) found the urate clearance to be lower in gouty subjects, suggesting that the susceptibility to hyperuricaemia has a renal mechanism. Even in Maoris with a normal serum uric acid the renal clearance of urate was similar to the values obtained in gouty British males. Similar observations have been made in Filipinos (Decker et al, 1968). This trait might explain the fundamental tendency of Polynesians, Melanesians, MalayoPolynesians and Malayo-Mongoloids to hyperuricaemia. The overall prevalence rates of gout in these populations in males varies from 1 to 10% depending on affluence, Westernized lifestyle and longer life-expectancy. The risk of gout in these peoples is significantly increased with a move to a Western diet and lifestyle, leading to obesity which aggravates their natural tendency to hyperuricaemia. Simmonds et al (1994) have documented that Polynesian women are also at greater risk for hyperuricaemia and gout than their Caucasian counterparts, due to reduced renal clearance of uric acid. In Africa, sporadic case reports before the 1980s appeared to indicate that gout was a rare disease (Kibukamusoke, 1968; Fleischmann and Adadevoh, 1973; Beighton et al, 1977) although unawareness and under-diagnosis are likely explanations for the low recording rates before the 1980s (Lutalo, 1985). Social and economic stratification appears to be irrelevant (Kanyerezi and Greenwood, 1984; Mody and Naidoo, 1984; Lutalo, 1985; Bileckot et al, 1991). There have been very few population surveys for gout in Africa and even these may not indicate its true prevalence. A survey in South Africa failed to identify any black patient with gout (Beighton et al, 1977). However, the hospital-based report from the same urban area picked up 11 patients over 38 months (Lowenthal and Dymond, 1977). Studies from Africain the 1980s show that gout is increasingly observed in hospitals and clinics, for example,
GOUT AND HYPERURICAEMIA
87
7-9% of patients attending specialized rheumatology clinics in Uganda and Zimbabwe, respectively, have gout (Kanyerezi and Greenwood, 1984; Stein and Davies, 1990). Among the chronic rheumatic diseases, excluding osteoarthritis, gout is second only to rheumatoid arthritis in prevalence in Zimbabwe (Lutalo, 1985). The disease was diagnosed in 71 of 1821 patients attending a medical outpatient clinic over a period of 2 years in Togo (Mijiyawa et al, 1992). A large series of 118 patients has been reported from Durban, South Africa (Cassim et al, 1991). In Africa, gout is associated with alcohol consumption across the entire social and economic stratum. All patients in Zimbabwe were average to heavy drinkers (Lutalo and Mabonga, 1992; Lutalo, 1993). This strong association with alcohol has been noted by several workers in Uganda (Kibukamusoke, 1968), the Congo (Bileckot et al, 1991) and Togo (Mijiyawa et al, 1992). This is in contrast to the finding in the UK where only 37% were regular drinkers (Graham and Scott, 1970) and to the situation in rural Java where alcohol is rarely consumed in significant quantities. Pre-menopausal women rarely exhibit clinical gout and the disease was less commonly observed in Polynesian and Javanese females. Male predominance is observed also in Africa, where the frequency of gout is 11 times greater in Nigerian males than females (Fleischmann and Adadevoh, 1973), 19 times in Congolese (Bileckot et al, 1991) and 6.7 times in Zimbabweans (Lutalo, 1993); in Togo the disease has been reported in men only (Mijiyawa et al, 1992). In Caucasian females polyarticular gout is not uncommonly precipitated by diuretics (Scott and Higgens, 1992). Chronic use of diuretics is rare in rural populations in the tropics, but in urban areas diuretics are widely used in the treatment of hypertension. URIC ACID The uric acid level of adult ethnic males in Oceania (Polynesians, Melanesians Malayo-Polynesians and Malayo-Mongoloids) is higher than most other populations studied (Table 2). All three ethnic groups in Malaysia, Malays, Tamil and Chinese show higher mean serum uric acid (SUA) levels compared with most Caucasian populations whereas black Africans, Japanese and American Indians have generally lower values than Caucasian populations. Acculturation has led to higher SUA levels in Filipinos and Malayo-Mongoloids (Decker et al, 1968), Tokelauans and Polynesians (Stanhope and Prior, 1979) and Chinese (Mongoloids). Recent Indonesian data has shown 2.9% of men to have SUA levels of 535.5 ~mol/1 (9 mg%) or greater and 30% of these had clinical gout (Darmawan et al, 1992). In a study from the USA about 2.3% had SUA levels of 535.5 txmol/1 (9 mg%) or greater but none had clinical gout (Glynn et al, 1983). Different levels of pathological SUA have been considered for different localities in Africa. In the Sudan 358.4 ixmol/1 (6 mg%) was considered to be the upper limit of normal in men (Ibrahim, 1975). In Uganda 10% of those tested had had values above this mean (Kanyerezi and Greenwood, 1984).
88
J. D A R M A W A N A N D S. K. L U T A L O
The SUA level in patients with clinical gout may also vary among different localities. In Nigeria 11.6% of patients who had an SUA of 358.4 txmol/1 (6 mg%) and above had clinical gout (Fleischmann and Adadevoh, 1973), while the mean SUA in gout patients in Zimbabwe was 588 + 138 txmol/1 (Lutalo 1993). CLINICAL FEATURES Gout is a disease which results from a sustained state of hyperuricaemia leading in some cases to monosodium urate monohydrate (sodium urate) crystal deposition resulting in acute arthritis, tophi and renal calculi. The diagnosis of gout based on the demonstration of birefringent sodium urate crystals from an effusion of an affected joint or tissue lesion is desirable but not always possible in the tropics where facilities may be inadequate. It is therefore important to have a simplified criteria for diagnosis of gout as shown below: (A)
Demonstration of sodium urate crystals in an effusion of the affected joint or tissue.
(B)
Presence of any two of the following: 1. history or observation of podagra; 2. history or observation of one abrupt attack of monoarthritis; 3. tophus; 4. response to colchicine within 48 h.
or
Sodium urate crystals are best demonstrated by polarized light microscopy where the needle-shaped crystals show birefringence. Where this special microscope is unavailable, a less sensitive test of viewing a drop of unanticoagulated synovial fluid on a slide under a cover slip using an ordinary light microscope will detect needle-shaped crystals. The uric acid level, if elevated, may be an additional help but the local prevailing levels in men and women have to be known to be interpreted correctly. The uric acid, of course, may be normal during acute attacks but is always raised in the inter-critical period. The level is known to be higher ordinarily in Polynesians than Caucasians and blacks in tropical Africa. Radiologically, bony defects with sclerotic sharply defined circular margins may be seen in chronic gout. Tophi are usually radiolucent unless there is superadded calcium deposition. X-ray facilities are usually available even in district hospitals in tropical Africa. One should, however, distinguish the lesions from those of tuberculosis of bone and rheumatoid arthritis. ACUTE GOUT The clinical presentation of gout in the tropics is much the same as in the developed countries with a few subtle differences (Bwanali et al, 1991; Mijiyawa et al, 1992; Lutalo, 1993). This is a disease diagnosed predominantly in men in their fifth decade of life with hyperuricaemia and who give a
GOUT AND HYPERURICAEMIA
89
history of alcohol excess. The Zimbabwe study showed that the male to female ratio was 6.7:1, the mean age at diagnosis was 44 + 8 years old, men have a mean serum uric acid at diagnosis of 558 + 138 ~xmol/1and all patients were moderate to heavy alcohol drinkers (Lutalo, 1993). A sudden attack of pain in the first metatarsal phalangeal joint, swollen, excruciatingly tender with distended veins without reddening in a hyperpigmented person (podagra) was seen in 78.2% of patients. The knee was afflicted in 73.6% of patients. It is important to distinguish this presentation from septic arthritis and cellulitis. Incision and drainage has been attempted inadvertantly in the hope of draining pus. Scarce resources have also been wasted on antibiotics in the false belief of treating pyogenic cellulitis. The frequency of individual joint attacks was as follows: ankle/foot 52.2%, wrist/hand joint 34.8% and elbows 30.8%. The shoulder joint was affected in a few cases in those patients whose occupation involved heavy manual labour. Polyarticular attacks of gout have also been noted in other studies (Mody and Naidoo, 1984; Bileckot et al, 1991). CHRONIC GOUT If gout is untreated, urates are deposited to produce chalky tophi over the joints, in bursae and in the pinnae of the ears. Whereas advanced tophaceous gout is now relatively uncommon in developed countries due to established usage of effective anti-hyperuricaemia drugs early in the disease, it is still common in the tropics. 30.4% of patients in Zimbabwe (Lutalo, 1993), 47% in South African blacks (Mody and Naidoo, 1984) and 28% in Togo (Mijiyawa et al, 1992) had tophi at diagnosis (Figure 1). After 20-30 years of untreated gout tophi may be so big that initial surgical excision of the lumps, in addition to uricosuric drug therapy, may be indicated.
Figure 1. Tophi in an Africanmale.
90
J. DARMAWAN AND S. K. LUTALO
Ulceration and secondary infection are common. The Indonesian data show gouty arthritis to be a disease of males over 45 years of age. Polyarticular disease is more common than monoarticular (3/1), probably due to lack of recognition of early disease. Big (Figure 2) or multiple tophi (Figure 3) are more common in remote rural areas. In urban areas tophi are less common
Figure 2. Big tophi in a Javanese male.
Figure 3. Multiple tophi in an Indonesian male.
GOUT AND HYPERURICAEMIA
91
and smaller due to earlier recognition and effective treatment. One author (J.D.) has observed in rural Java, in a random sample of 25 of 180 communities and health centres in the province of North Selawesi (formerly Celebes), Indonesia, 125 men with polyarticular gout and multiple tophi were identified and it is estimated that there are over 1400 males with multiple tophi affecting elbows, fingers, knees, ankles and toes in this region. MORTALITY IN GOUT Increased mortality of patients with chronic gout is known to be due to complications resulting from sodium urate nephropathy, urolithiasis, renal failure and associated conditions such as hypertension, hyperlipidaemia (type IV/obesity) coronary heart disease and diabetes mellitus (Abbott et al, 1988). Hypertension was an associated condition in 73.9% of gout patients in Zimbabwe (Lutalo, 1993) and in 42% of the South African blacks (Mody and Naidoo, 1984). In Zimbabwean patients 69.9% were also obese. Ischaemic heart disease in tropical Africans, however, is still relatively uncommon except in those who have adopted a Western lifestyle and diet. Renal impairment is seen in about one-third of gouty patients in South Africa and the Congo (Mody and Naidoo, 1984; Bileckot et al, 1991). End stage chronic renal failure was present in 4.4% of the patients in Zimbabwe (Lutalo, 1993). With point prevalence rates of gout ranging from 10 to 100/1000 adult males, the detection and control of gout is of urgent relevance for the almost 400 million Malayo-Polynesians and Malayo-Mongoloids in South-East Asia and the Polynesians and Melanesians in the Pacific Islands, especially those who have adjusted to the lifestyle of the West or have migrated to industrialized countries. TREATMENT Treatment of gout should be along the usual lines with an anti-inflammatory agent for the acute attack, followed by appropriate uricosuric therapy (Groff et al, 1990). We do not advocate the treatment of hyperuricaemia in the absence of clinical gout. Furthermore, the treatment of obesity and reduction of excessive alcohol consumption is a high priority public health measure designed not only to reduce hyperuricaemia and gout but make inroads into the appalling problems of hypertension, obesity and diabetes which now afflict many Pacific communities and are a future threat to communities faced with urbanization and a changing lifestyle. OTHER CRYSTALS ASSOCIATED WITH ARTHROPATHY
These include acute pseudo-gout and chronic pyrophosphate arthropathy, acute calcific periarthritis and chronic hydroxyapatite arthritis (Fam, 1992). There is little information on these entities in the tropical setting but there is
92
J. DARMAWAN AND S. K. LUTALO
Figure 4. Chronic pylophosphate arthropathy disease in knees and wrists of a 65-year-old Tanzanian male.
Figure 5. Left shoulder calcific periarthritis in a 65-year-old Tanzanian diabetic.
no doubt that they do occur and examples of African patients with chronic pyrophosphate arthropathy and acute periarthritic arthritis are shown in Figures 4 and 5, respectively. SUMMARY
We have recounted the remarkable story of gout and hyperuricaemia in the indigenous populations of the Pacific and noted the recent identification of
GOUT AND HYPERURICAEMIA
93
the same problem in communities in rural Indonesia. Gout is increasingly recognized in African populations, especially in urban centres. There is no doubt that gout is 'alive and well' and presents a continuing challenge to future generations in developing countries.
REFERENCES Abbott RD, Brand FD, Kannel WB et al (1988) Gout and coronary heart disease: the Framingham study. Journal of Clinical Epidemiology 41: 23%242. Beaudet F, de Medici R, Magny P e t al (1993) Acute apatite podagra with negative birefringent spherulites in the synovial fluid. (Journal) 20: 1975-1978. Beighton P, Solomon L, Soskoine CL & Sweet MB (1977) Rheumatic disorders in the South African Negro. Part IV. Gout and hyperuricaemia. South African Medical Journal 51" 969-972. Bileckot R, Ntsiba H, Mbongo JA et al (1991) Epidemiological and clinical aspects of gout in equatorial Africa. Revue Du Rheumatisme et De Maladies Osteo-Articulaires 58:863-867 (in French). Bwanali K, Mbuyi M & Kapita B (1991) Osteoarthrosis, gout and arthritis rheumatoid in internal medicine in Kinshasa. Revue Du Rheumatisme et de Maladies Osteo-Articulaires 58" 105-111 (in French). Cassim B, Mody GM, Deendayalu VG & Hammond MG (1991) Gout in African Blacks--A Clinical and Genetic Study. Abstract: First AFLAR Congress of Rheumatology, 23-27 September 1991, Cairo, Egypt. Darmawan J, Valkenburg HA, Muirden KD & Wigley RD (1992) The epidemiology of gout and hyperuricemia in a rural population of Java. Journal of Rheumatology 19: 1595-1599. Decker JL, Healey LA & Skeith MD (1968) Ethnic variations in serum uric acid: Filipino hyperuricaemia, the result of hereditary and environmental factors. In Bennet PH & Wood PHN (eds) Population Studies of the Rheumatic Diseases, pp 336-342. Amsterdam: Excerpta Medica. Faro A G (1992) Calcium pyrophosphate crystal deposition diseases. Current Opinion in Rheumatology 4: 574-582. Fleischmann V & Adadevoh BK (1973) Hyperuricaemia and gout in Nigerians. Tropical and Geographical Medicine 25: 255-261. Gibson T, Waterworth R, Hatfield P e t al (1984) Hyperuricaemia, gout and kidney function in New Zealand Maori men. British Journal of Rheumatology 23" 276-282. Glynn RJ, Campion EW & Silbert RJ (1983) Trends in serum uric acid levels, 1961-1980. Arthritis and Rheumatology 26" 87-93. Graham R & Scott JT (1970) Clinical survey of 354 patients with gout. Annals of Rheumatic Diseases 29: 461-468. Groff GD, Franck WA & Raddatz D A (1990) Systemic therapy for acute gout: A clinical trial and review of the literature. Seminars in Arthritis and Rheumatism 19: 329-336. Ibrahim SA (1975) Hyperuricaemia in Sudanese. Journal of Tropical Medicine and Hygiene 78: 47-48. Kanyerezi BR & Greenwood BM (1984) Diseases of joints, connective tissue and mtlscle. In Parry EHO (ed.) Principles of Medicine in Africa (2rid edn), p 939. Oxford: Oxford University Press. Kellgren JH (1964) The epidemiology of rheumatic diseases. Annals of Rheumatic Diseases 23: 109-122. Kibukamusoke JW (1968) Gout in Africans. East African Medical Journal 45z 378-382. Lennane GAQ, Rose BS & Isdale IC (1960) Gout in the Maori. Annals of Rheumatic Diseases 19: 120-125. Lowenthal MN & Dymond ID (1977) Gout and hyperuricaemia in blacks (letter). South African Medical Journal 52: 832. Lutalo SK (1985) Chronic inflammatory rheumatic diseases in black Zimbabweans. Annals of Rheumatic Diseases 44: 121-125.
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Lutalo SK (1993) Gout: an experience from Zimbabwe. Central African Journal of Medicine 39: 60-62. Lutalo SK & Mabonga N (1992) A clinical assessment of the consequences of alcohol consumption in 'communal' drinkers in the Zimbabwean Midlands. Central African Journal of Medicine 38: 380-384. Mijiyawa M, Djagnikpo K, Dagbovie K & Agbetra A (1992) Gout in Togolese patients. Revue Du Rheumatism Et De Maladies Osteo-Articulaires 59:473-477 (in French). Mody GM & Naidoo PD (1984) Gout in South African blacks. Annals o f the Rheumatic Diseases 43: 394-397. Prior IAM, Rose BS, Harvey HPB & Davidson F (1966) Hyperuricaemia, gout and diabetic abnormalities in Polynesian people. Lancet 1: 333-338. Prior IAM, Welby TJ, Ostbye T et al (1987) Migration and gout: the Tokelau Island migrant study. British Medical Journal 295: 457-461. Scott JT & Higgens CS (1992) Diuretic induced gout: a multifactorial condition. Annals o f the Rheumatic Diseases 51: 259-261. Simmonds HA, McBride MB, Hatfield PJ et al (1994) Polynesian women are also at risk for hyperuricaemia and gout because of a genetic defect in renal urate handling. British Journal o f Rheumatology 33: 932-937. Stanhope JM & Prior IAM (1979) The Tokelau Island migrant study: Alcohol consumption in two environments. New Zealand Medical Journal 90: 419-421. Stein M & Davies P (1990) Rheumatic disorders in Zimbabwe: a prospective analysis of patients attending a rheumatic diseases clinic. Annals o f the Rheumatic Diseases 49: 400-402. Wohlmann AS (1914) The Mineral Water and Spas of New Zealand. New Zealand: Government Printer. Zimmet PZ, Whitehouse S, Jackson L & Thoma K (1978) High prevalence of hyperuricaemia and gout in an urbanised Micronesian population. British Medical Journal 1: 1237-1239.
Nowadays in industrialized countries gout is perhaps treated with a certain degree of complacency. Recognized from ancient times, this articular scourge has relinquished its dominant place in medicine, partly through the recognition of early disease and the availability of safe, effective remedies. However, in some tropical developing populations, gout is a cause of increasing morbidity. Studies in these populations continue to provide tantalizing insights into the environmental and hereditary factors associated with hyperuricaemia and gout.
EPIDEMIOLOGY Caution should be exercised in the interpretation and comparison of point prevalence rates of gout in different populations, surveyed by various study designs, diagnosed by different criteria, influenced by diurnal and seasonal variations in serum urate concentration, and affected by inter-observer variation. In addition, small sample sizes do generate wide 95% confidence intervals, crystal identification in epidemiology surveys is practically impossible and cases of non-urate arthropathy may be included in such studies. Despite these drawbacks, available data point to some striking and real differences in the prevalence rates of gout (Table 1) and hyperuricaemia (Table 2) in various populations. Gout was not recorded in Polynesians of the South Pacific islands and New Zealand before 1914 (Wohlmann, 1914). Yet, nowadays, some of the highest rates of gout and hyperuricaemia in the world are to be found in these populations. The Maoris of New Zealand have a predisposition to hyperuricaemia and the overall frequency of gout in men, recorded at around 10% in studies in the 1960s (Prior et al, 1966) is still today at this level with around one in three males over the age of 40 years affected, i.e. more than eight times that of age counterparts in Europe and North America (Gibson et al, 1984) and New Zealanders of European stock (Lennane et al, 1960). Elsewhere in the Pacific Island of Nauru 64% of men and 60% of women aged 20 years and over have hyperuricaemia, the highest prevalence rates yet reported for any population (Zimmet et al, 1978). The prevalence BailliOre's Clinical Rheumatology--
Vol. 9, No. I, February1995 ISBN0-7020-1946-1
83 Copyright9 1995,by Bailli6reTindall All rights of reproductionin any formreserved
J. D A R M A W A N A N D S. K. L U T A L O
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rate of gout in men is 7%. The authors suggest that the high prevalence of gout is related to environmental changes from the traditional island style of living to one of almost complete Westernization, a point dramatically reinforced in a 14 year incidence study of Tokelauans (Prior et al, 1987). From a base-line of around 20:1000, the prevalence rose to 51:1000 in migrated Tokelauan males (to New Zealand) compared to a slight fall to 15:1000 in non-migrated males over the same period. The relative risk of gout was nine times higher in the migrant Tokelauans, placing them in the same risk class as the New Zealand Maoris. Age-specific incidence studies also revealed that gout occurs at an earlier age in migrant men. These prevalence and incidence changes in clinical gout were matched by significantly higher serum uric acid concentrations in migrants compared with non-migrants. Kellgren (1964) has suggested that the indigenous Polynesian inhabitants of the Pacific basin form one large, potentially gouty family, an observation which may extend to the Malayo-Polynesians of Java. Darmawan et al (1992) have found rates of gout and hyperuricaemia in rural Javanese to be similar to that of non-migrant Tokelauans and higher than most Caucasian populations in the absence of alcohol consumption and a very low meat consumption. There was no association either with wealth, social class or body mass index. These observations imply that other, probably genetic, factors operate in these indigenous populations. In a study of Maori men, Gibson et al (1984) found the urate clearance to be lower in gouty subjects, suggesting that the susceptibility to hyperuricaemia has a renal mechanism. Even in Maoris with a normal serum uric acid the renal clearance of urate was similar to the values obtained in gouty British males. Similar observations have been made in Filipinos (Decker et al, 1968). This trait might explain the fundamental tendency of Polynesians, Melanesians, MalayoPolynesians and Malayo-Mongoloids to hyperuricaemia. The overall prevalence rates of gout in these populations in males varies from 1 to 10% depending on affluence, Westernized lifestyle and longer life-expectancy. The risk of gout in these peoples is significantly increased with a move to a Western diet and lifestyle, leading to obesity which aggravates their natural tendency to hyperuricaemia. Simmonds et al (1994) have documented that Polynesian women are also at greater risk for hyperuricaemia and gout than their Caucasian counterparts, due to reduced renal clearance of uric acid. In Africa, sporadic case reports before the 1980s appeared to indicate that gout was a rare disease (Kibukamusoke, 1968; Fleischmann and Adadevoh, 1973; Beighton et al, 1977) although unawareness and under-diagnosis are likely explanations for the low recording rates before the 1980s (Lutalo, 1985). Social and economic stratification appears to be irrelevant (Kanyerezi and Greenwood, 1984; Mody and Naidoo, 1984; Lutalo, 1985; Bileckot et al, 1991). There have been very few population surveys for gout in Africa and even these may not indicate its true prevalence. A survey in South Africa failed to identify any black patient with gout (Beighton et al, 1977). However, the hospital-based report from the same urban area picked up 11 patients over 38 months (Lowenthal and Dymond, 1977). Studies from Africain the 1980s show that gout is increasingly observed in hospitals and clinics, for example,
GOUT AND HYPERURICAEMIA
87
7-9% of patients attending specialized rheumatology clinics in Uganda and Zimbabwe, respectively, have gout (Kanyerezi and Greenwood, 1984; Stein and Davies, 1990). Among the chronic rheumatic diseases, excluding osteoarthritis, gout is second only to rheumatoid arthritis in prevalence in Zimbabwe (Lutalo, 1985). The disease was diagnosed in 71 of 1821 patients attending a medical outpatient clinic over a period of 2 years in Togo (Mijiyawa et al, 1992). A large series of 118 patients has been reported from Durban, South Africa (Cassim et al, 1991). In Africa, gout is associated with alcohol consumption across the entire social and economic stratum. All patients in Zimbabwe were average to heavy drinkers (Lutalo and Mabonga, 1992; Lutalo, 1993). This strong association with alcohol has been noted by several workers in Uganda (Kibukamusoke, 1968), the Congo (Bileckot et al, 1991) and Togo (Mijiyawa et al, 1992). This is in contrast to the finding in the UK where only 37% were regular drinkers (Graham and Scott, 1970) and to the situation in rural Java where alcohol is rarely consumed in significant quantities. Pre-menopausal women rarely exhibit clinical gout and the disease was less commonly observed in Polynesian and Javanese females. Male predominance is observed also in Africa, where the frequency of gout is 11 times greater in Nigerian males than females (Fleischmann and Adadevoh, 1973), 19 times in Congolese (Bileckot et al, 1991) and 6.7 times in Zimbabweans (Lutalo, 1993); in Togo the disease has been reported in men only (Mijiyawa et al, 1992). In Caucasian females polyarticular gout is not uncommonly precipitated by diuretics (Scott and Higgens, 1992). Chronic use of diuretics is rare in rural populations in the tropics, but in urban areas diuretics are widely used in the treatment of hypertension. URIC ACID The uric acid level of adult ethnic males in Oceania (Polynesians, Melanesians Malayo-Polynesians and Malayo-Mongoloids) is higher than most other populations studied (Table 2). All three ethnic groups in Malaysia, Malays, Tamil and Chinese show higher mean serum uric acid (SUA) levels compared with most Caucasian populations whereas black Africans, Japanese and American Indians have generally lower values than Caucasian populations. Acculturation has led to higher SUA levels in Filipinos and Malayo-Mongoloids (Decker et al, 1968), Tokelauans and Polynesians (Stanhope and Prior, 1979) and Chinese (Mongoloids). Recent Indonesian data has shown 2.9% of men to have SUA levels of 535.5 ~mol/1 (9 mg%) or greater and 30% of these had clinical gout (Darmawan et al, 1992). In a study from the USA about 2.3% had SUA levels of 535.5 txmol/1 (9 mg%) or greater but none had clinical gout (Glynn et al, 1983). Different levels of pathological SUA have been considered for different localities in Africa. In the Sudan 358.4 ixmol/1 (6 mg%) was considered to be the upper limit of normal in men (Ibrahim, 1975). In Uganda 10% of those tested had had values above this mean (Kanyerezi and Greenwood, 1984).
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The SUA level in patients with clinical gout may also vary among different localities. In Nigeria 11.6% of patients who had an SUA of 358.4 txmol/1 (6 mg%) and above had clinical gout (Fleischmann and Adadevoh, 1973), while the mean SUA in gout patients in Zimbabwe was 588 + 138 txmol/1 (Lutalo 1993). CLINICAL FEATURES Gout is a disease which results from a sustained state of hyperuricaemia leading in some cases to monosodium urate monohydrate (sodium urate) crystal deposition resulting in acute arthritis, tophi and renal calculi. The diagnosis of gout based on the demonstration of birefringent sodium urate crystals from an effusion of an affected joint or tissue lesion is desirable but not always possible in the tropics where facilities may be inadequate. It is therefore important to have a simplified criteria for diagnosis of gout as shown below: (A)
Demonstration of sodium urate crystals in an effusion of the affected joint or tissue.
(B)
Presence of any two of the following: 1. history or observation of podagra; 2. history or observation of one abrupt attack of monoarthritis; 3. tophus; 4. response to colchicine within 48 h.
or
Sodium urate crystals are best demonstrated by polarized light microscopy where the needle-shaped crystals show birefringence. Where this special microscope is unavailable, a less sensitive test of viewing a drop of unanticoagulated synovial fluid on a slide under a cover slip using an ordinary light microscope will detect needle-shaped crystals. The uric acid level, if elevated, may be an additional help but the local prevailing levels in men and women have to be known to be interpreted correctly. The uric acid, of course, may be normal during acute attacks but is always raised in the inter-critical period. The level is known to be higher ordinarily in Polynesians than Caucasians and blacks in tropical Africa. Radiologically, bony defects with sclerotic sharply defined circular margins may be seen in chronic gout. Tophi are usually radiolucent unless there is superadded calcium deposition. X-ray facilities are usually available even in district hospitals in tropical Africa. One should, however, distinguish the lesions from those of tuberculosis of bone and rheumatoid arthritis. ACUTE GOUT The clinical presentation of gout in the tropics is much the same as in the developed countries with a few subtle differences (Bwanali et al, 1991; Mijiyawa et al, 1992; Lutalo, 1993). This is a disease diagnosed predominantly in men in their fifth decade of life with hyperuricaemia and who give a
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history of alcohol excess. The Zimbabwe study showed that the male to female ratio was 6.7:1, the mean age at diagnosis was 44 + 8 years old, men have a mean serum uric acid at diagnosis of 558 + 138 ~xmol/1and all patients were moderate to heavy alcohol drinkers (Lutalo, 1993). A sudden attack of pain in the first metatarsal phalangeal joint, swollen, excruciatingly tender with distended veins without reddening in a hyperpigmented person (podagra) was seen in 78.2% of patients. The knee was afflicted in 73.6% of patients. It is important to distinguish this presentation from septic arthritis and cellulitis. Incision and drainage has been attempted inadvertantly in the hope of draining pus. Scarce resources have also been wasted on antibiotics in the false belief of treating pyogenic cellulitis. The frequency of individual joint attacks was as follows: ankle/foot 52.2%, wrist/hand joint 34.8% and elbows 30.8%. The shoulder joint was affected in a few cases in those patients whose occupation involved heavy manual labour. Polyarticular attacks of gout have also been noted in other studies (Mody and Naidoo, 1984; Bileckot et al, 1991). CHRONIC GOUT If gout is untreated, urates are deposited to produce chalky tophi over the joints, in bursae and in the pinnae of the ears. Whereas advanced tophaceous gout is now relatively uncommon in developed countries due to established usage of effective anti-hyperuricaemia drugs early in the disease, it is still common in the tropics. 30.4% of patients in Zimbabwe (Lutalo, 1993), 47% in South African blacks (Mody and Naidoo, 1984) and 28% in Togo (Mijiyawa et al, 1992) had tophi at diagnosis (Figure 1). After 20-30 years of untreated gout tophi may be so big that initial surgical excision of the lumps, in addition to uricosuric drug therapy, may be indicated.
Figure 1. Tophi in an Africanmale.
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Ulceration and secondary infection are common. The Indonesian data show gouty arthritis to be a disease of males over 45 years of age. Polyarticular disease is more common than monoarticular (3/1), probably due to lack of recognition of early disease. Big (Figure 2) or multiple tophi (Figure 3) are more common in remote rural areas. In urban areas tophi are less common
Figure 2. Big tophi in a Javanese male.
Figure 3. Multiple tophi in an Indonesian male.
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and smaller due to earlier recognition and effective treatment. One author (J.D.) has observed in rural Java, in a random sample of 25 of 180 communities and health centres in the province of North Selawesi (formerly Celebes), Indonesia, 125 men with polyarticular gout and multiple tophi were identified and it is estimated that there are over 1400 males with multiple tophi affecting elbows, fingers, knees, ankles and toes in this region. MORTALITY IN GOUT Increased mortality of patients with chronic gout is known to be due to complications resulting from sodium urate nephropathy, urolithiasis, renal failure and associated conditions such as hypertension, hyperlipidaemia (type IV/obesity) coronary heart disease and diabetes mellitus (Abbott et al, 1988). Hypertension was an associated condition in 73.9% of gout patients in Zimbabwe (Lutalo, 1993) and in 42% of the South African blacks (Mody and Naidoo, 1984). In Zimbabwean patients 69.9% were also obese. Ischaemic heart disease in tropical Africans, however, is still relatively uncommon except in those who have adopted a Western lifestyle and diet. Renal impairment is seen in about one-third of gouty patients in South Africa and the Congo (Mody and Naidoo, 1984; Bileckot et al, 1991). End stage chronic renal failure was present in 4.4% of the patients in Zimbabwe (Lutalo, 1993). With point prevalence rates of gout ranging from 10 to 100/1000 adult males, the detection and control of gout is of urgent relevance for the almost 400 million Malayo-Polynesians and Malayo-Mongoloids in South-East Asia and the Polynesians and Melanesians in the Pacific Islands, especially those who have adjusted to the lifestyle of the West or have migrated to industrialized countries. TREATMENT Treatment of gout should be along the usual lines with an anti-inflammatory agent for the acute attack, followed by appropriate uricosuric therapy (Groff et al, 1990). We do not advocate the treatment of hyperuricaemia in the absence of clinical gout. Furthermore, the treatment of obesity and reduction of excessive alcohol consumption is a high priority public health measure designed not only to reduce hyperuricaemia and gout but make inroads into the appalling problems of hypertension, obesity and diabetes which now afflict many Pacific communities and are a future threat to communities faced with urbanization and a changing lifestyle. OTHER CRYSTALS ASSOCIATED WITH ARTHROPATHY
These include acute pseudo-gout and chronic pyrophosphate arthropathy, acute calcific periarthritis and chronic hydroxyapatite arthritis (Fam, 1992). There is little information on these entities in the tropical setting but there is
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Figure 4. Chronic pylophosphate arthropathy disease in knees and wrists of a 65-year-old Tanzanian male.
Figure 5. Left shoulder calcific periarthritis in a 65-year-old Tanzanian diabetic.
no doubt that they do occur and examples of African patients with chronic pyrophosphate arthropathy and acute periarthritic arthritis are shown in Figures 4 and 5, respectively. SUMMARY
We have recounted the remarkable story of gout and hyperuricaemia in the indigenous populations of the Pacific and noted the recent identification of
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the same problem in communities in rural Indonesia. Gout is increasingly recognized in African populations, especially in urban centres. There is no doubt that gout is 'alive and well' and presents a continuing challenge to future generations in developing countries.
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