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Gout is a form of inflammatory arthritis caused by uric acid precipitation in and around joints. This painful condition was first identified in ancient times by Egyptians around 2640 BC. Hippocrates first wrote about this disorder in 400 BC.1,2 Prolonged hyperuricemia is the main risk factor for gout.Hyperuricemia can be caused by either excessive intake of a purine rich diet or inadequate excretion of uric acid by the kidneys. Human beings lack the enzyme uricase which converts uric acid into water soluble allantoin which is more readily excreted.3 Genetic studies have identified association between polymorphism in the GLUT9 (SLC2A9) gene and URAT1 (SLC22CA12) gene to be key regulators and transporters of uric acid.Genetic variations in these enzymes are identified as risk factors for hyperuricemia and gout.4,5 Other well recognised associations for hyperuricemia and gout include age, diabetes mellitus, hypertension, metabolic syndrome, renal disease, cardiovascular diseases and medications like diuretics.Gout is predominantly a disease of males, but in recent times, there has been an increase in prevalence in women. The reported male to female ratio is approximately 7:1 to 9:1 but in people over the age of 65 this ratio is reduced to 3:1.6-8 Gout is considered rare in premenopausal women as the estrogenic hormones have a mild uricosuric effect and therefore protective against hyperuricemia and gout. During menopause the estrogen levels drop and women with risk factors become more likely to develop hyperuricemia and gout.9However, in our clinical practice we have noticed an increasing frequency of young women presenting with acute flares of gout.The objective of this study was to describe the clinical characteristics of female patients with gout, assess risk factors for gout in this cohort and identify any differences between pre- and postmenopausal women with this diagnosis who present to secondary care in South Auckland.Methods We retrospectively reviewed the records of female patients with a diagnosis of gout using the International Classification of Diseases-9 (ICD-9 codes 274.0, 274.8, 274.9), who were seen at Counties Manukau District Health Board (CMDHB), South Auckland, New Zealand, between July 2007 and July 2008. Demographic data, information on relevant comorbidities and diuretic use were collected. Comorbidities of interest were obesity, hypertension, congestive heart failure, dyslipidemia, diabetes mellitus and renal impairment. Obesity was defined as body mass index (BMI) >30kg/m2; renal impairment was defined as estimated glomerular filtration rate (eGFR) of <60mls/min using the Modification of Diet in Renal Disease (MDRD) formula.10 The menstrual status of women was not usually recorded in the hospital medical charts therefore we used an age cut-off of 50 years (average age of menopause in our population) as a surrogate marker for pre-and postmenopausal status. We collected laboratory data on lipid levels, serum urate and glomerular filtration rate. The use of urate-lowering therapy was determined from the electronic medical records. Statistical analysis—Statistical analysis was conducted using OpenEpi (version 2.3.1) software. Paired t-test (2 sided) was used to compare differences among means. Chi-squared was used to compare differences in proportions. One-way ANOVA used to compare differences in means when there were more than 2 samples. All reported p values less than 0.05 were considered statistically significant. Results Between 1 July 2007 and 31 July 2008, 509 patients presented to CMDHB for management of gout. This included inpatient as well as outpatient visits. Table 1 shows the gender and ethnic distribution of the study population. Among the 509 patients, 122 (24%) were female. Fourteen female patients (11.5%) were either 50 years or younger and 108 (88.5%) were over 50 years of age. Table 2 shows a comparison of the ethnicity, the traditional risk factors and prescribed treatment between the two age groups. Table1. Gender and ethnic distribution of patients with gout presenting to secondary care at Counties Manukau District Health Board in the period 1 July 2007 and 31 July 2008 Ethnicity Total n (%) Males n (%) Females n (%) M:F ratio Māori Pacific people Europeans Others 129 (25) 237 (47) 115 (23) 28 (6) 87 (22) 190 (49) 86 (22) 24 (6) 42(34) 47 (39) 29 (24) 4 (3) 2:1 4:1 3:1 6:1 Total n (%) 509 (100) 387 (100) 122 (100) 3:1 Table 2. Description of women with gout stratified by age Characteristics Age ≤50 years (n=14) Age >50 (n=108) P value Mean age (range) 41 (23-50) 71.5 (51-95) Ethnicity Māori n (%) 6 (43) 36 (33.3) 0.67 Pacific n (%) 8 (57) 39 (36.1) 0.22 European n (%) 0 (0) 29 (26) 0.035 Others n (%) 0 (0) 4 (3.7) 1.00 Risk factors Mean BMI Hypertension no (%) Diabetes mellitus Renal impairment CHF Dyslipidemia Ischemic heart disease Three or more comorbidities 43.5 9 (64.3) 6 (42.9) 11 (78.6) 6 (43) 5 (35.7) 1 ( 7.0) 9 (64) 33.1 83 (77) 54 (50) 76 (70) 40 (37) 60 (55) 46 (43) 70 (64.8) 0.002 0.24 0.41 0.39 0.44 0.13 0.01 0.97 SUA mean (range) 0.54 (0.4-0.8) 0.48 (0.22-0.92) 0.17 Treatment Allopurinol no (%) Uricosuric agent 3 (21.4) 2 (14.3) 45 (42) 1 (1.0) 0.12 0.03 Table 3. Risk factors for the three major ethnic groups Characteristics European Māori Pacific people P value Numbers (%) 29 (24.58) 42 (35.59) 47 (39.83) Average age (range) 78.9 (52-95) 60.5 (23-85) 60.93 (27-83) 0.10 Mean BMI (range) 31.6 (20.6-40) 34.1 (24-51.2) 37.1 (21-77) <0.001 Hypertension No. (%) 19 (65.5) 33 (78.6) 35 (74.5) 0.47 Diabetes mellitus No. (%) 7 (24.14) 21 (50) 23 (48.90) 0.06 Renal impairment No. (%) 18 (62) 27 (64.3) 39 (83) 0.07 CHF no (%) 11 (37.9) 18 (42.9) 17 (36.2) 0.80 IHD no (%) 16 (55) 17 (40.5) 13 (27.7) 0.06 Dyslipidemia No. (%) 20 (69) 19 (45.2) 25 (53.2) 0.14 Diuretic use No. (%) 16 (55) 23 (54.8) 20 (42.6) 0.42 Mean SUA (range) 0.45 (0.22-0.71) 0.51 (0.28-0.92) 0.50 (0.27-0.81) 0.42 Treatment Allopurinol No (%) 10 (34.5) 16 (38) 21 ( 44.7) 0.65 Uricosuric agent No (%) 0 (0) 0 (0) 3 ( 6.4) 0.10 In the ‘pre-menopausal’ age group (≤ 50 years), 43% were Māori and 57% were Pacific people. There was no European or people of other ethnic group represented in this age group. In the older age group (> 50 years), 26% of the population were Europeans, 33.3% were Māori, 36.1% were Pacific People and 4% were of other ethnic group (predominantly Asian). Every patient in the ‘pre-menopausal’ age group had a comorbidity that predisposed them to gout. Renal impairment (78.6%) and hypertension (64.3%) were the two most common co morbidities in the ≤50 age group. Renal impairment was attributed to hypertensive disease in 57% and glomerulonephritis in 21%. Congestive heart failure and diabetes mellitus were present in 43% of patients who were ≤50 years old. The underlying cause for congestive heart failure was either rheumatic valvular heart disease or non-ischemic cardiomyopathy. Comorbidities seen in the older age group were hypertension (77%), renal impairment (70%), dyslipidemia (55%), diabetes mellitus (42.95%) and ischemic heart disease (43%). The presence of ischemic heart disease was more common in older women (43% vs 7%, P<0.01), whereas the mean BMI was significantly higher in the younger age group (BMI 43.5 vs. 33.1, P<0.01). Diuretic use was similar between the age groups (approximately 50% in both groups). The mean serum uric acid was not statistically different between the 2 age groups. Medication to lower uric acid was prescribed in 5 (35.7%) of patients in the younger age group and 46 (42.59%) of patients in the older age group. Allopurinol was the drug of choice and only 3 (2.68%) received uricosuric agents. When risk factors for different ethnic groups were compared, statistically significant difference was noted in the mean BMI. Obesity, defined as a BMI of greater than 30 was noted in 64 % of the less than 50 age group and 39% in the older age group, with the Pacific People having highest mean BMI (37.1) followed by M&

Summary

Abstract

Aim

To describe the clinical characteristics of female patients with gout, assess risk factors in this group and to identify any differences between pre- and postmenopausal women with this diagnosis.

Method

We retrospectively reviewed the case records of all women who were seen with gout in a secondary care setting (inpatient and outpatient) at Counties Manukau District Health Board between July 2007 and July 2008. Demographic data, risk factors for gout and information on urate-lowering therapy was collected. A cut-off of less than and equal to 50 years was used to estimate pre-menopausal status.

Results

122/509 (24%) of patients seen with gout were female. Fourteen female patients were less than and equal to 50 years of age; all of these patients were either Maori (43%) or of Pacific Island ethnicity (57%). Comorbidities in those less than and equale to 50 years old were renal impairment (78.6%), hypertension (64.3%), congestive heart failure (43%) and diabetes mellitus (42.9%). Comorbidities in women >50 years old were similar: hypertension (77%), renal impairment (70%), dyslipidemia (53%) and diabetes mellitus (50%). Ischemic heart disease was more common in older women (43% vs 7%), P

Conclusion

Women who develop gout are more likely to be over the age of 50, have other comorbidities and be on diuretics. In comparison, younger women who develop gout have similar risk factors but tended to have a higher body mass index and are more likely to be of Maori or Pacific Island ethnicity.

Author Information

Sunil Kumar, Rheumatologist, Department of Rheumatology, Counties Manukau District Health Board, Auckland; Rajiv Gupta, Rheumatologist, Department of Rheumatology, Counties Manukau District Health Board, Auckland; Ravi Suppiah, Rheumatologist, Department of Rheumatology, Auckland City Hospital and Middlemore Hospital, Auckland

Acknowledgements

Correspondence

Dr Sunil Kumar, Department of Rheumatology, Counties Manukau District Health Board, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand.

Correspondence Email

skumar@middlemore.co.nz

Competing Interests

None known.

Benedek TG, Rodnan GP. A brief history of the rheumatic disease. Bull Rheum Dis 1982;32(6):59-68.Nuki G, Simkin PA. A concise history of gout and hyperuricemia and their treatment. Arthritis Res Ther 2006;8(suppl 1):S1.Vogt B. Urate oxidase (rasburicase) for treatment of severe tophaceous gout. Nephrol Dial Transplant 2005;20:431-433.Brandstatter A, Kiechl S, Kollerits, et al. Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI. Diabetes care: Aug 2008;31(8):1662-1667.Richette, Pascal; Bardin, Thomas. Gout. Lancet 2010;375(9711):318-328.Mahajan A, Tandon VR, Sharma S, Jandial C. Gout and menopause. J K Science 2007;9(1):50-51.Souza AWS, Fernandes V, Ferrari AJL. Female gout: Clinical and laboratory features. J. Rheumatol 2005; 32 (11):2186-2188.Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in US women - The Third National Health and Nutrition Examination Survey. Arthritis Res Ther. 2008;10(5):120.Harrold LR, Yood RA, Mikuls TR, et al. Sex differences in gout epidemiology: evaluation and treatment. Ann Rheum Dis 2006;65:1368-1372.Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Int Med 1999;130(6):461-70.Wong K, Jackson G. The changing demography of Counties Manukau District health.http://www.cmdhb.org.nz/About_CMDHB/Planning/Health-Status/Population/2008/changing-demography-report.pdfKlemp P, Stansfield SA, Castle B, Robertson MC. Gout is on the increase in New Zealand. Ann Rheum Dis. 1997;56(1):22-6.Hollis-Moffatt JE, Xu X, Dalbeth N, et al. A role for the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Maori, Pacific Island and Caucasian case-control cohorts. Arthritis Rheum 2009;60:3485-92.Choi H, Curhan G. Adiposity, hypertension, diuretic use and risk of incident gout in women- The Nurses Health Study. ACR Annual scientific meeting 2005; Abstract 1977.Lally EV, Ho G Jr, Kaplan SR. The clinical spectrum of gouty arthritis in women. Arch Intern Med. 1986 Nov;146(11):2221-5.Suppiah R, Dissanayake A, Dalbeth N. High prevalence of gout in patients with Type 2 diabetes: male sex, renal impairment, and diuretic use are major risk factors N Z Med J. 2008;121 (1283). http://journal.nzma.org.nz/journal/121-1283/3293/

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Gout is a form of inflammatory arthritis caused by uric acid precipitation in and around joints. This painful condition was first identified in ancient times by Egyptians around 2640 BC. Hippocrates first wrote about this disorder in 400 BC.1,2 Prolonged hyperuricemia is the main risk factor for gout.Hyperuricemia can be caused by either excessive intake of a purine rich diet or inadequate excretion of uric acid by the kidneys. Human beings lack the enzyme uricase which converts uric acid into water soluble allantoin which is more readily excreted.3 Genetic studies have identified association between polymorphism in the GLUT9 (SLC2A9) gene and URAT1 (SLC22CA12) gene to be key regulators and transporters of uric acid.Genetic variations in these enzymes are identified as risk factors for hyperuricemia and gout.4,5 Other well recognised associations for hyperuricemia and gout include age, diabetes mellitus, hypertension, metabolic syndrome, renal disease, cardiovascular diseases and medications like diuretics.Gout is predominantly a disease of males, but in recent times, there has been an increase in prevalence in women. The reported male to female ratio is approximately 7:1 to 9:1 but in people over the age of 65 this ratio is reduced to 3:1.6-8 Gout is considered rare in premenopausal women as the estrogenic hormones have a mild uricosuric effect and therefore protective against hyperuricemia and gout. During menopause the estrogen levels drop and women with risk factors become more likely to develop hyperuricemia and gout.9However, in our clinical practice we have noticed an increasing frequency of young women presenting with acute flares of gout.The objective of this study was to describe the clinical characteristics of female patients with gout, assess risk factors for gout in this cohort and identify any differences between pre- and postmenopausal women with this diagnosis who present to secondary care in South Auckland.Methods We retrospectively reviewed the records of female patients with a diagnosis of gout using the International Classification of Diseases-9 (ICD-9 codes 274.0, 274.8, 274.9), who were seen at Counties Manukau District Health Board (CMDHB), South Auckland, New Zealand, between July 2007 and July 2008. Demographic data, information on relevant comorbidities and diuretic use were collected. Comorbidities of interest were obesity, hypertension, congestive heart failure, dyslipidemia, diabetes mellitus and renal impairment. Obesity was defined as body mass index (BMI) >30kg/m2; renal impairment was defined as estimated glomerular filtration rate (eGFR) of <60mls/min using the Modification of Diet in Renal Disease (MDRD) formula.10 The menstrual status of women was not usually recorded in the hospital medical charts therefore we used an age cut-off of 50 years (average age of menopause in our population) as a surrogate marker for pre-and postmenopausal status. We collected laboratory data on lipid levels, serum urate and glomerular filtration rate. The use of urate-lowering therapy was determined from the electronic medical records. Statistical analysis—Statistical analysis was conducted using OpenEpi (version 2.3.1) software. Paired t-test (2 sided) was used to compare differences among means. Chi-squared was used to compare differences in proportions. One-way ANOVA used to compare differences in means when there were more than 2 samples. All reported p values less than 0.05 were considered statistically significant. Results Between 1 July 2007 and 31 July 2008, 509 patients presented to CMDHB for management of gout. This included inpatient as well as outpatient visits. Table 1 shows the gender and ethnic distribution of the study population. Among the 509 patients, 122 (24%) were female. Fourteen female patients (11.5%) were either 50 years or younger and 108 (88.5%) were over 50 years of age. Table 2 shows a comparison of the ethnicity, the traditional risk factors and prescribed treatment between the two age groups. Table1. Gender and ethnic distribution of patients with gout presenting to secondary care at Counties Manukau District Health Board in the period 1 July 2007 and 31 July 2008 Ethnicity Total n (%) Males n (%) Females n (%) M:F ratio Māori Pacific people Europeans Others 129 (25) 237 (47) 115 (23) 28 (6) 87 (22) 190 (49) 86 (22) 24 (6) 42(34) 47 (39) 29 (24) 4 (3) 2:1 4:1 3:1 6:1 Total n (%) 509 (100) 387 (100) 122 (100) 3:1 Table 2. Description of women with gout stratified by age Characteristics Age ≤50 years (n=14) Age >50 (n=108) P value Mean age (range) 41 (23-50) 71.5 (51-95) Ethnicity Māori n (%) 6 (43) 36 (33.3) 0.67 Pacific n (%) 8 (57) 39 (36.1) 0.22 European n (%) 0 (0) 29 (26) 0.035 Others n (%) 0 (0) 4 (3.7) 1.00 Risk factors Mean BMI Hypertension no (%) Diabetes mellitus Renal impairment CHF Dyslipidemia Ischemic heart disease Three or more comorbidities 43.5 9 (64.3) 6 (42.9) 11 (78.6) 6 (43) 5 (35.7) 1 ( 7.0) 9 (64) 33.1 83 (77) 54 (50) 76 (70) 40 (37) 60 (55) 46 (43) 70 (64.8) 0.002 0.24 0.41 0.39 0.44 0.13 0.01 0.97 SUA mean (range) 0.54 (0.4-0.8) 0.48 (0.22-0.92) 0.17 Treatment Allopurinol no (%) Uricosuric agent 3 (21.4) 2 (14.3) 45 (42) 1 (1.0) 0.12 0.03 Table 3. Risk factors for the three major ethnic groups Characteristics European Māori Pacific people P value Numbers (%) 29 (24.58) 42 (35.59) 47 (39.83) Average age (range) 78.9 (52-95) 60.5 (23-85) 60.93 (27-83) 0.10 Mean BMI (range) 31.6 (20.6-40) 34.1 (24-51.2) 37.1 (21-77) <0.001 Hypertension No. (%) 19 (65.5) 33 (78.6) 35 (74.5) 0.47 Diabetes mellitus No. (%) 7 (24.14) 21 (50) 23 (48.90) 0.06 Renal impairment No. (%) 18 (62) 27 (64.3) 39 (83) 0.07 CHF no (%) 11 (37.9) 18 (42.9) 17 (36.2) 0.80 IHD no (%) 16 (55) 17 (40.5) 13 (27.7) 0.06 Dyslipidemia No. (%) 20 (69) 19 (45.2) 25 (53.2) 0.14 Diuretic use No. (%) 16 (55) 23 (54.8) 20 (42.6) 0.42 Mean SUA (range) 0.45 (0.22-0.71) 0.51 (0.28-0.92) 0.50 (0.27-0.81) 0.42 Treatment Allopurinol No (%) 10 (34.5) 16 (38) 21 ( 44.7) 0.65 Uricosuric agent No (%) 0 (0) 0 (0) 3 ( 6.4) 0.10 In the ‘pre-menopausal’ age group (≤ 50 years), 43% were Māori and 57% were Pacific people. There was no European or people of other ethnic group represented in this age group. In the older age group (> 50 years), 26% of the population were Europeans, 33.3% were Māori, 36.1% were Pacific People and 4% were of other ethnic group (predominantly Asian). Every patient in the ‘pre-menopausal’ age group had a comorbidity that predisposed them to gout. Renal impairment (78.6%) and hypertension (64.3%) were the two most common co morbidities in the ≤50 age group. Renal impairment was attributed to hypertensive disease in 57% and glomerulonephritis in 21%. Congestive heart failure and diabetes mellitus were present in 43% of patients who were ≤50 years old. The underlying cause for congestive heart failure was either rheumatic valvular heart disease or non-ischemic cardiomyopathy. Comorbidities seen in the older age group were hypertension (77%), renal impairment (70%), dyslipidemia (55%), diabetes mellitus (42.95%) and ischemic heart disease (43%). The presence of ischemic heart disease was more common in older women (43% vs 7%, P<0.01), whereas the mean BMI was significantly higher in the younger age group (BMI 43.5 vs. 33.1, P<0.01). Diuretic use was similar between the age groups (approximately 50% in both groups). The mean serum uric acid was not statistically different between the 2 age groups. Medication to lower uric acid was prescribed in 5 (35.7%) of patients in the younger age group and 46 (42.59%) of patients in the older age group. Allopurinol was the drug of choice and only 3 (2.68%) received uricosuric agents. When risk factors for different ethnic groups were compared, statistically significant difference was noted in the mean BMI. Obesity, defined as a BMI of greater than 30 was noted in 64 % of the less than 50 age group and 39% in the older age group, with the Pacific People having highest mean BMI (37.1) followed by M&

Summary

Abstract

Aim

To describe the clinical characteristics of female patients with gout, assess risk factors in this group and to identify any differences between pre- and postmenopausal women with this diagnosis.

Method

We retrospectively reviewed the case records of all women who were seen with gout in a secondary care setting (inpatient and outpatient) at Counties Manukau District Health Board between July 2007 and July 2008. Demographic data, risk factors for gout and information on urate-lowering therapy was collected. A cut-off of less than and equal to 50 years was used to estimate pre-menopausal status.

Results

122/509 (24%) of patients seen with gout were female. Fourteen female patients were less than and equal to 50 years of age; all of these patients were either Maori (43%) or of Pacific Island ethnicity (57%). Comorbidities in those less than and equale to 50 years old were renal impairment (78.6%), hypertension (64.3%), congestive heart failure (43%) and diabetes mellitus (42.9%). Comorbidities in women >50 years old were similar: hypertension (77%), renal impairment (70%), dyslipidemia (53%) and diabetes mellitus (50%). Ischemic heart disease was more common in older women (43% vs 7%), P

Conclusion

Women who develop gout are more likely to be over the age of 50, have other comorbidities and be on diuretics. In comparison, younger women who develop gout have similar risk factors but tended to have a higher body mass index and are more likely to be of Maori or Pacific Island ethnicity.

Author Information

Sunil Kumar, Rheumatologist, Department of Rheumatology, Counties Manukau District Health Board, Auckland; Rajiv Gupta, Rheumatologist, Department of Rheumatology, Counties Manukau District Health Board, Auckland; Ravi Suppiah, Rheumatologist, Department of Rheumatology, Auckland City Hospital and Middlemore Hospital, Auckland

Acknowledgements

Correspondence

Dr Sunil Kumar, Department of Rheumatology, Counties Manukau District Health Board, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand.

Correspondence Email

skumar@middlemore.co.nz

Competing Interests

None known.

Benedek TG, Rodnan GP. A brief history of the rheumatic disease. Bull Rheum Dis 1982;32(6):59-68.Nuki G, Simkin PA. A concise history of gout and hyperuricemia and their treatment. Arthritis Res Ther 2006;8(suppl 1):S1.Vogt B. Urate oxidase (rasburicase) for treatment of severe tophaceous gout. Nephrol Dial Transplant 2005;20:431-433.Brandstatter A, Kiechl S, Kollerits, et al. Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI. Diabetes care: Aug 2008;31(8):1662-1667.Richette, Pascal; Bardin, Thomas. Gout. Lancet 2010;375(9711):318-328.Mahajan A, Tandon VR, Sharma S, Jandial C. Gout and menopause. J K Science 2007;9(1):50-51.Souza AWS, Fernandes V, Ferrari AJL. Female gout: Clinical and laboratory features. J. Rheumatol 2005; 32 (11):2186-2188.Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in US women - The Third National Health and Nutrition Examination Survey. Arthritis Res Ther. 2008;10(5):120.Harrold LR, Yood RA, Mikuls TR, et al. Sex differences in gout epidemiology: evaluation and treatment. Ann Rheum Dis 2006;65:1368-1372.Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Int Med 1999;130(6):461-70.Wong K, Jackson G. The changing demography of Counties Manukau District health.http://www.cmdhb.org.nz/About_CMDHB/Planning/Health-Status/Population/2008/changing-demography-report.pdfKlemp P, Stansfield SA, Castle B, Robertson MC. Gout is on the increase in New Zealand. Ann Rheum Dis. 1997;56(1):22-6.Hollis-Moffatt JE, Xu X, Dalbeth N, et al. A role for the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Maori, Pacific Island and Caucasian case-control cohorts. Arthritis Rheum 2009;60:3485-92.Choi H, Curhan G. Adiposity, hypertension, diuretic use and risk of incident gout in women- The Nurses Health Study. ACR Annual scientific meeting 2005; Abstract 1977.Lally EV, Ho G Jr, Kaplan SR. The clinical spectrum of gouty arthritis in women. Arch Intern Med. 1986 Nov;146(11):2221-5.Suppiah R, Dissanayake A, Dalbeth N. High prevalence of gout in patients with Type 2 diabetes: male sex, renal impairment, and diuretic use are major risk factors N Z Med J. 2008;121 (1283). http://journal.nzma.org.nz/journal/121-1283/3293/

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Gout is a form of inflammatory arthritis caused by uric acid precipitation in and around joints. This painful condition was first identified in ancient times by Egyptians around 2640 BC. Hippocrates first wrote about this disorder in 400 BC.1,2 Prolonged hyperuricemia is the main risk factor for gout.Hyperuricemia can be caused by either excessive intake of a purine rich diet or inadequate excretion of uric acid by the kidneys. Human beings lack the enzyme uricase which converts uric acid into water soluble allantoin which is more readily excreted.3 Genetic studies have identified association between polymorphism in the GLUT9 (SLC2A9) gene and URAT1 (SLC22CA12) gene to be key regulators and transporters of uric acid.Genetic variations in these enzymes are identified as risk factors for hyperuricemia and gout.4,5 Other well recognised associations for hyperuricemia and gout include age, diabetes mellitus, hypertension, metabolic syndrome, renal disease, cardiovascular diseases and medications like diuretics.Gout is predominantly a disease of males, but in recent times, there has been an increase in prevalence in women. The reported male to female ratio is approximately 7:1 to 9:1 but in people over the age of 65 this ratio is reduced to 3:1.6-8 Gout is considered rare in premenopausal women as the estrogenic hormones have a mild uricosuric effect and therefore protective against hyperuricemia and gout. During menopause the estrogen levels drop and women with risk factors become more likely to develop hyperuricemia and gout.9However, in our clinical practice we have noticed an increasing frequency of young women presenting with acute flares of gout.The objective of this study was to describe the clinical characteristics of female patients with gout, assess risk factors for gout in this cohort and identify any differences between pre- and postmenopausal women with this diagnosis who present to secondary care in South Auckland.Methods We retrospectively reviewed the records of female patients with a diagnosis of gout using the International Classification of Diseases-9 (ICD-9 codes 274.0, 274.8, 274.9), who were seen at Counties Manukau District Health Board (CMDHB), South Auckland, New Zealand, between July 2007 and July 2008. Demographic data, information on relevant comorbidities and diuretic use were collected. Comorbidities of interest were obesity, hypertension, congestive heart failure, dyslipidemia, diabetes mellitus and renal impairment. Obesity was defined as body mass index (BMI) >30kg/m2; renal impairment was defined as estimated glomerular filtration rate (eGFR) of <60mls/min using the Modification of Diet in Renal Disease (MDRD) formula.10 The menstrual status of women was not usually recorded in the hospital medical charts therefore we used an age cut-off of 50 years (average age of menopause in our population) as a surrogate marker for pre-and postmenopausal status. We collected laboratory data on lipid levels, serum urate and glomerular filtration rate. The use of urate-lowering therapy was determined from the electronic medical records. Statistical analysis—Statistical analysis was conducted using OpenEpi (version 2.3.1) software. Paired t-test (2 sided) was used to compare differences among means. Chi-squared was used to compare differences in proportions. One-way ANOVA used to compare differences in means when there were more than 2 samples. All reported p values less than 0.05 were considered statistically significant. Results Between 1 July 2007 and 31 July 2008, 509 patients presented to CMDHB for management of gout. This included inpatient as well as outpatient visits. Table 1 shows the gender and ethnic distribution of the study population. Among the 509 patients, 122 (24%) were female. Fourteen female patients (11.5%) were either 50 years or younger and 108 (88.5%) were over 50 years of age. Table 2 shows a comparison of the ethnicity, the traditional risk factors and prescribed treatment between the two age groups. Table1. Gender and ethnic distribution of patients with gout presenting to secondary care at Counties Manukau District Health Board in the period 1 July 2007 and 31 July 2008 Ethnicity Total n (%) Males n (%) Females n (%) M:F ratio Māori Pacific people Europeans Others 129 (25) 237 (47) 115 (23) 28 (6) 87 (22) 190 (49) 86 (22) 24 (6) 42(34) 47 (39) 29 (24) 4 (3) 2:1 4:1 3:1 6:1 Total n (%) 509 (100) 387 (100) 122 (100) 3:1 Table 2. Description of women with gout stratified by age Characteristics Age ≤50 years (n=14) Age >50 (n=108) P value Mean age (range) 41 (23-50) 71.5 (51-95) Ethnicity Māori n (%) 6 (43) 36 (33.3) 0.67 Pacific n (%) 8 (57) 39 (36.1) 0.22 European n (%) 0 (0) 29 (26) 0.035 Others n (%) 0 (0) 4 (3.7) 1.00 Risk factors Mean BMI Hypertension no (%) Diabetes mellitus Renal impairment CHF Dyslipidemia Ischemic heart disease Three or more comorbidities 43.5 9 (64.3) 6 (42.9) 11 (78.6) 6 (43) 5 (35.7) 1 ( 7.0) 9 (64) 33.1 83 (77) 54 (50) 76 (70) 40 (37) 60 (55) 46 (43) 70 (64.8) 0.002 0.24 0.41 0.39 0.44 0.13 0.01 0.97 SUA mean (range) 0.54 (0.4-0.8) 0.48 (0.22-0.92) 0.17 Treatment Allopurinol no (%) Uricosuric agent 3 (21.4) 2 (14.3) 45 (42) 1 (1.0) 0.12 0.03 Table 3. Risk factors for the three major ethnic groups Characteristics European Māori Pacific people P value Numbers (%) 29 (24.58) 42 (35.59) 47 (39.83) Average age (range) 78.9 (52-95) 60.5 (23-85) 60.93 (27-83) 0.10 Mean BMI (range) 31.6 (20.6-40) 34.1 (24-51.2) 37.1 (21-77) <0.001 Hypertension No. (%) 19 (65.5) 33 (78.6) 35 (74.5) 0.47 Diabetes mellitus No. (%) 7 (24.14) 21 (50) 23 (48.90) 0.06 Renal impairment No. (%) 18 (62) 27 (64.3) 39 (83) 0.07 CHF no (%) 11 (37.9) 18 (42.9) 17 (36.2) 0.80 IHD no (%) 16 (55) 17 (40.5) 13 (27.7) 0.06 Dyslipidemia No. (%) 20 (69) 19 (45.2) 25 (53.2) 0.14 Diuretic use No. (%) 16 (55) 23 (54.8) 20 (42.6) 0.42 Mean SUA (range) 0.45 (0.22-0.71) 0.51 (0.28-0.92) 0.50 (0.27-0.81) 0.42 Treatment Allopurinol No (%) 10 (34.5) 16 (38) 21 ( 44.7) 0.65 Uricosuric agent No (%) 0 (0) 0 (0) 3 ( 6.4) 0.10 In the ‘pre-menopausal’ age group (≤ 50 years), 43% were Māori and 57% were Pacific people. There was no European or people of other ethnic group represented in this age group. In the older age group (> 50 years), 26% of the population were Europeans, 33.3% were Māori, 36.1% were Pacific People and 4% were of other ethnic group (predominantly Asian). Every patient in the ‘pre-menopausal’ age group had a comorbidity that predisposed them to gout. Renal impairment (78.6%) and hypertension (64.3%) were the two most common co morbidities in the ≤50 age group. Renal impairment was attributed to hypertensive disease in 57% and glomerulonephritis in 21%. Congestive heart failure and diabetes mellitus were present in 43% of patients who were ≤50 years old. The underlying cause for congestive heart failure was either rheumatic valvular heart disease or non-ischemic cardiomyopathy. Comorbidities seen in the older age group were hypertension (77%), renal impairment (70%), dyslipidemia (55%), diabetes mellitus (42.95%) and ischemic heart disease (43%). The presence of ischemic heart disease was more common in older women (43% vs 7%, P<0.01), whereas the mean BMI was significantly higher in the younger age group (BMI 43.5 vs. 33.1, P<0.01). Diuretic use was similar between the age groups (approximately 50% in both groups). The mean serum uric acid was not statistically different between the 2 age groups. Medication to lower uric acid was prescribed in 5 (35.7%) of patients in the younger age group and 46 (42.59%) of patients in the older age group. Allopurinol was the drug of choice and only 3 (2.68%) received uricosuric agents. When risk factors for different ethnic groups were compared, statistically significant difference was noted in the mean BMI. Obesity, defined as a BMI of greater than 30 was noted in 64 % of the less than 50 age group and 39% in the older age group, with the Pacific People having highest mean BMI (37.1) followed by M&

Summary

Abstract

Aim

To describe the clinical characteristics of female patients with gout, assess risk factors in this group and to identify any differences between pre- and postmenopausal women with this diagnosis.

Method

We retrospectively reviewed the case records of all women who were seen with gout in a secondary care setting (inpatient and outpatient) at Counties Manukau District Health Board between July 2007 and July 2008. Demographic data, risk factors for gout and information on urate-lowering therapy was collected. A cut-off of less than and equal to 50 years was used to estimate pre-menopausal status.

Results

122/509 (24%) of patients seen with gout were female. Fourteen female patients were less than and equal to 50 years of age; all of these patients were either Maori (43%) or of Pacific Island ethnicity (57%). Comorbidities in those less than and equale to 50 years old were renal impairment (78.6%), hypertension (64.3%), congestive heart failure (43%) and diabetes mellitus (42.9%). Comorbidities in women >50 years old were similar: hypertension (77%), renal impairment (70%), dyslipidemia (53%) and diabetes mellitus (50%). Ischemic heart disease was more common in older women (43% vs 7%), P

Conclusion

Women who develop gout are more likely to be over the age of 50, have other comorbidities and be on diuretics. In comparison, younger women who develop gout have similar risk factors but tended to have a higher body mass index and are more likely to be of Maori or Pacific Island ethnicity.

Author Information

Sunil Kumar, Rheumatologist, Department of Rheumatology, Counties Manukau District Health Board, Auckland; Rajiv Gupta, Rheumatologist, Department of Rheumatology, Counties Manukau District Health Board, Auckland; Ravi Suppiah, Rheumatologist, Department of Rheumatology, Auckland City Hospital and Middlemore Hospital, Auckland

Acknowledgements

Correspondence

Dr Sunil Kumar, Department of Rheumatology, Counties Manukau District Health Board, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand.

Correspondence Email

skumar@middlemore.co.nz

Competing Interests

None known.

Benedek TG, Rodnan GP. A brief history of the rheumatic disease. Bull Rheum Dis 1982;32(6):59-68.Nuki G, Simkin PA. A concise history of gout and hyperuricemia and their treatment. Arthritis Res Ther 2006;8(suppl 1):S1.Vogt B. Urate oxidase (rasburicase) for treatment of severe tophaceous gout. Nephrol Dial Transplant 2005;20:431-433.Brandstatter A, Kiechl S, Kollerits, et al. Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI. Diabetes care: Aug 2008;31(8):1662-1667.Richette, Pascal; Bardin, Thomas. Gout. Lancet 2010;375(9711):318-328.Mahajan A, Tandon VR, Sharma S, Jandial C. Gout and menopause. J K Science 2007;9(1):50-51.Souza AWS, Fernandes V, Ferrari AJL. Female gout: Clinical and laboratory features. J. Rheumatol 2005; 32 (11):2186-2188.Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in US women - The Third National Health and Nutrition Examination Survey. Arthritis Res Ther. 2008;10(5):120.Harrold LR, Yood RA, Mikuls TR, et al. Sex differences in gout epidemiology: evaluation and treatment. Ann Rheum Dis 2006;65:1368-1372.Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Int Med 1999;130(6):461-70.Wong K, Jackson G. The changing demography of Counties Manukau District health.http://www.cmdhb.org.nz/About_CMDHB/Planning/Health-Status/Population/2008/changing-demography-report.pdfKlemp P, Stansfield SA, Castle B, Robertson MC. Gout is on the increase in New Zealand. Ann Rheum Dis. 1997;56(1):22-6.Hollis-Moffatt JE, Xu X, Dalbeth N, et al. A role for the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Maori, Pacific Island and Caucasian case-control cohorts. Arthritis Rheum 2009;60:3485-92.Choi H, Curhan G. Adiposity, hypertension, diuretic use and risk of incident gout in women- The Nurses Health Study. ACR Annual scientific meeting 2005; Abstract 1977.Lally EV, Ho G Jr, Kaplan SR. The clinical spectrum of gouty arthritis in women. Arch Intern Med. 1986 Nov;146(11):2221-5.Suppiah R, Dissanayake A, Dalbeth N. High prevalence of gout in patients with Type 2 diabetes: male sex, renal impairment, and diuretic use are major risk factors N Z Med J. 2008;121 (1283). http://journal.nzma.org.nz/journal/121-1283/3293/

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