Hyperuricemia in patients with chronic plaque psoriasis Paolo Gisondi, MD,a Giovanni Targher, MD,b Anna Cagalli, MD,a and Giampiero Girolomoni, MDa Verona, Italy Background: Few studies have examined the association between elevated serum uric acid (SUA) levels and psoriasis, and their results have been inconclusive because most of these studies did not take into account the confounding effects of coexisting features of the metabolic syndrome. Objective: We compared the prevalence of hyperuricemia and SUA levels between psoriatic patients and control individuals. Methods: Levels of SUA were measured in 119 consecutive psoriatic patients and 119 control individuals matched for age, sex, and body mass index. Results: Compared with control subjects, psoriatic patients had higher SUA levels (5.61 6 1.6 vs 4.87 6 1.4 mg/dL; P \ .001) and a remarkably greater prevalence of asymptomatic hyperuricemia (19% vs 7%; P \ .001). Multivariate logistic regression analysis revealed that psoriasis was the strongest predictor of hyperuricemia (odds ratio 3.20; 95% confidence interval 1.32-7.58; P \.01) after adjusting for age, sex, and metabolic syndrome features. Limitations: The cross-sectional design of this study does not allow us to draw any conclusion about a causal relation between psoriasis and hyperuricemia. Conclusions: Hyperuricemia is a common finding in psoriatic patients. Its treatment might be clinically useful for the global treatment of patients. ( J Am Acad Dermatol 2014;70:127-30.) Key words: body mass index; cardiovascular risk; hyperuricemia; psoriasis; psoriatic arthritis; uric acid.
P
soriasis is a chronic inflammatory disease that is often associated with features of the metabolic syndrome, including obesity, dyslipidemia, and type 2 diabetes.1-3 Psoriasis is also linked to an increased risk of incident cardiovascular disease (CVD).4,5 Similarly to psoriasis, growing epidemiologic evidence suggests that elevated levels of serum uric acid (SUA) are strongly associated with features of the metabolic syndrome and predict increased risk of CVD mortality and morbidity.6,7 Few studies have examined the relationship between psoriasis and hyperuricemia and their results have been inconclusive as most of these studies did not take into account the confounding effects of coexisting features of the metabolic syndrome.8-11 The aim of this study was to compare circulating levels of SUA and the prevalence of
From the Department of Medicine, Section of Dermatology,a and Section of Endocrinology, Diabetes, and Metabolism,b University of Verona. Supported by the Ministero della Salute, and the Ministero dell’Istruzione, Universita e Ricerca Scientifica (Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale), and by the Association for Dermatological Research. Conflicts of interest: None declared. Accepted for publication September 6, 2013. Reprints not available from the authors.
Abbreviations used: BMI: CVD: PASI: PsA: SUA:
body mass index cardiovascular disease Psoriasis Area and Severity Index psoriatic arthritis serum uric acid
hyperuricemia between psoriatic patients and control subjects.
METHODS Participants We enrolled 119 psoriatic patients, who consecutively attended our joined dermatology and rheumatology outpatient clinic, specifically dedicated to Correspondence to: Paolo Gisondi, MD, Department of Medicine, Section of Dermatology and Venereology, University of Verona, Piazzale Stefani 1, I-37126 Verona, Italy. E-mail: paolo.gisondi@ univr.it. Published online November 1, 2013. 0190-9622/$36.00 Ó 2013 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2013.09.005
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psoriasis and psoriatic arthritis (PsA), during the 126 mg/dL, hypoglycemic treatment, or both. period from January to June 2012. We included all Hypertriglyceridemia and hypercholesterolemia patients with a clinical diagnosis of psoriasis (ie, were defined as serum triglycerides 150 mg/dL or lasting at least 6 months) who either were never greater and total cholesterol 240 mg/dL or greater, or treated or stopped their systemic antipsoriatic treatlipid-lowering treatment. Metabolic syndrome was ments at least 3 months before the investigation. defined according to the widely used criteria proPatients with excessive alcohol consumption, adposed by the Adult Treatment Panel-III definition.14 vanced chronic kidney disHyperuricemia was defined ease, and those who were as a SUA level 7 mg/dL or CAPSULE SUMMARY taking any medications higher in men and 6 mg/dL known to affect SUA level or higher in women or alloPsoriasis is closely associated with (except for allopurinol), inpurinol use. features of the metabolic syndrome, cluding diuretics, salicylates, which may favor the development of ketoconazole, theophylline, Statistical analysis hyperuricemia. pyrazinamide, and ethambuData are presented as Hyperuricemia predisposes patients to tol, were not included in the means 6 SD or percentages. gouty arthritis and is now considered as study, as per study protocol. Statistical analyses included an emerging risk factor for Information on daily alcohol the paired t test for means cardiovascular mortality and morbidity. consumption was obtained and McNemar test for profrom all participants by a portions because the 2 The prevalence of hyperuricemia is standardized questiongroups were matched. A mulremarkably greater in psoriatic patients naire.12 In particular, alcohol tivariable logistic regression than in age-, sex-, and weight-matched consumption was assessed analysis was performed to control subjects, and is independent of on the basis of the selfidentify the factors that were coexisting metabolic disorders. reported number of drinks independently associated consumed per day. The folwith hyperuricemia. Two lowing amounts of alcoholic beverages were considforced-entry multivariable regression models were ered 1 drink: 330 mL of beer (containing ;5% performed: a model adjusted for age, sex, psoriasis, alcohol), 150 mL of wine (containing ;12% alcohol), and metabolic syndrome (model 1); and a model and 40 mL of strong spirits (containing ;50% alcoadjusted for age, sex, psoriasis, and individual comhol). Overall, most of our psoriatic patients were ponents of metabolic syndrome (model 2). All analabstainers or drank only minimally ( # 2 drinks per yses were performed using a statistical package (SPSS day; n = 83; 69.8%), whereas 30.2% of them drank 3 to 19.0, IBM Corp, Armonk, NY) and statistical signifi4 drinks per day. No participants drank more than 4 cance was assessed at the 2-tailed .05 thresholds. drinks per day. Each patient was visited either by a dermatologist and a rheumatologist who assessed the RESULTS presence/absence of PsA using Classification Criteria Clinical characteristics of participants are shown in for Psoriatic Arthritis (CASPAR) criteria13 and/or gout. Table I. By study design, age, sex, and BMI were Diagnosis of psoriasis was clinical, and disease almost identical between psoriatic patients and conseverity was scored using the Psoriasis Area and trol subjects. Psoriatic patients were more likely to Severity Index (PASI). The control group consisted of have metabolic syndrome, hypertension, type 2 dia119 adult individuals, who were randomly selected in betes, and hypertriglyceridemia whereas smoking and a 1:1 ratio among a historical cohort of 756 nonhypercholesterolemia were not significantly different psoriatic subjects to be matched for age, sex, and between the 2 groups. Notably, psoriatic patients had body mass index (BMI) to psoriatic patients. significantly higher levels of SUA than control subjects. As shown in Fig 1, the prevalence of hyperuricemia was remarkably greater in psoriatic patients than in Clinical and laboratory variables control subjects. Results remained essentially unVenous blood was withdrawn in the morning changed even when those with established diabetes after an overnight fast. SUA and other biochemical (n = 26), PsA (n = 75), or both were excluded from blood measurements were determined by standard analysis or when participants were stratified by sex. laboratory procedures. Obesity was defined as BMI Also in this case, men and women with psoriasis had 30 kg/m2 or higher. Hypertension was defined as significantly higher SUA than their counterparts withblood pressure greater than or equal to 140/90 mm out the skin disease (6.01 6 1.6 vs 5.20 6 1.4 mg/dL in Hg or hypertension treatment. Diabetes was men and 4.47 6 1.4 vs 3.85 6 1.0 mg/dL in women). defined as fasting glycemia greater than or equal to d
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Table I. Main clinical characteristics of the study participants
Clinical characteristics
Sex, M/F Age, y BMI, kg/m2 Obesity, n (%) Current smokers, n (%) Hypertension, n (%) Type 2 diabetes, n (%) Hypercholesterolemia, n (%) Hypertriglyceridemia, n (%) Metabolic syndrome, n (%) Serum uric acid, mg/dL Serum creatinine, mg/dL Psoriasis duration, y PASI score No. of previous treatments for psoriasis, n PsA, n (%)
Psoriatic patients (n = 119)
Control subjects (n = 119)
P value
88/31 54.1 6 12 27.8 6 4.6 36 (30.2) 20 (16.8) 61 (51.3) 21 (17.6) 15 (12.6)
88/31 54.3 6 8 27.8 6 3.1 35 (29.4) 18 (15.1) 45 (37.8) 5 (4.2) 17 (14.3)
Matched Matched Matched Matched .81 \.01 \.001 .76
27 (22.7)
21 (17.6)
.06
40 (33.6)
26 (21.8)
\.01
5.61 6 1.6 4.87 6 1.4 \.001 0.92 6 0.2 0.89 6 0.2 .86 21.3 6 13 NA 11.2 6 9 NA 1.7 6 0.7 NA
75 (63.0)
NA
Data are presented as means 6 SD or percentages. Differences are tested by the unpaired t test or the x 2 test (for categorical variables). BMI, Body mass index; F, female; M, male; NA, not applicable; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis.
Fig 2. Serum uric acid levels in psoriatic patients and control subjects stratified by status of the metabolic syndrome (MetS ). * and **P \.001 for difference between the 2 groups. *Refers to the difference between psoriatic patients and controls among the group with the metabolic syndrome. **Refers to the difference between psoriatic patients and controls among the group without the metabolic syndrome.
categorical variable), independently of each other, were significant predictors of hyperuricemia. Interestingly, among psoriatic patients, SUA levels were significantly higher in patients with PASI score 10 or greater than in those with PASI score less than 10 (SUA: 5.9 6 1.6 vs 5.2 6 1.5 mg/dL; P \ .05). In addition, SUA was positively associated with BMI (r = 0.34; P \.001), serum triglyceride (r = 0.24; P \.01), and creatinine levels (r = 0.33; P \ .001), but it was not significantly associated with age, sex, and psoriasis duration (data not shown). Finally, no significant difference was found in SUA levels between patients with PsA and those with psoriasis alone (SUA: 5.6 6 1.6 vs 5.5 6 1.5 mg/dL; P = .60).
DISCUSSION
Fig 1. Prevalence of hyperuricemia in psoriatic patients and in age-, sex-, and body mass indexematched control subjects. *P \ .001 for difference between the 2 groups.
Similarly, results remained unchanged when participants were stratified by the presence of metabolic syndrome; psoriatic patients, irrespective of the presence of metabolic syndrome, had significantly higher SUA levels than control subjects (Fig 2). Notably, as shown in Table II, multivariable logistic regression analysis revealed that both psoriasis and metabolic syndrome (included as
In this case-control study, we found that the prevalence of asymptomatic hyperuricemia was approximately 3-fold higher in psoriatic patients than in matched control subjects (19% vs 7%). Interestingly, and more importantly, the multivariable regression analysis showed that psoriasis was the strongest predictor of hyperuricemia after adjusting for potential confounders, such as age, sex, BMI, and other features of metabolic syndrome. Although hyperuricemia in psoriatic patients could be simply a consequence of obesity and other coexisting metabolic disorders,1,6,7 our findings suggest that psoriasis itself might, at least in part, contribute directly to hyperuricemia. Kwon et al8 recently proposed that an increased epidermal cell turnover could be an important cause of raised SUA levels among psoriatic patients. Our findings of a significant, graded relationship between SUA levels
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Table II. Predictors of hyperuricemia in the whole sample of participants: multivariable logistic regression models Clinical characteristics
Age, y Sex, M vs F Psoriasis, yes vs no Metabolic syndrome, yes vs no BMI, kg/m2 Type 2 diabetes, yes vs no Hypertension, yes vs no Hypertriglyceridemia, yes vs no
Multivariable model 1
P value
Multivariable model 2
P value
1.04 (0.98-1.08) 2.16 (0.77-6.84) 3.15 (1.28-7.61) 2.24 (1.14-4.96) Not included Not included Not included Not included
.20 .18 \.01 \.05 -
1.03 (0.98-1.07) 2.19 (0.74-6.82) 3.20 (1.31-7.58) Not included 1.10 (0.98-1.22) 0.87 (0.33-2.75) 1.54 (0.66-3.70) 1.73 (0.94-2.86)
.26 .17 \.01 .14 .73 .36 .19
Sample size, n = 238. Results are expressed as odds ratio and 95% confidence intervals. Covariates included in the 2 multivariable regression models were as follows: model 1 = age, sex, presence of psoriasis, and metabolic syndrome; model 2 = age, sex, presence of psoriasis, BMI, type 2 diabetes mellitus, hypertension, and hypertriglyceridemia. BMI, Body mass index; F, female; M, male.
and PASI further support this conclusion. However, additional research is required to uncover other specific mechanisms by which psoriasis might contribute to the development of hyperuricemia (possibly through increased uric acid production, decreased urinary uric acid excretion, or both). Our findings may have important clinical implications. Elevated SUA causes gouty arthritis, which needs to be differentiated from PsA in clinical practice.15 In addition, elevated SUA is associated with increased carotid-artery intima-media thickness in patients with PsA,16 and independently predicts the development of both CVD events and mortality in nonpsoriatic populations.6,7 Although the crosssectional design of this study does not allow us to draw any conclusion about a causal relationship between psoriasis and hyperuricemia, we believe that SUA levels should be routinely measured in psoriatic patients, and that the pharmacologic treatment of asymptomatic hyperuricemia might also be clinically relevant to the global treatment of patients. In a cohort study of approximately 7000 individuals aged 60 years or older, the treatment of hyperuricemia with higher doses of allopurinol was significantly associated with lower risks of both CVD events and mortality.17 However, whether this could be also applied to psoriatic patients needs to be investigated in future large intervention clinical trials. REFERENCES 1. Sterry W, Strober BE, Menter A. Obesity in psoriasis: the metabolic, clinical and therapeutic implications: report of an interdisciplinary conference and review. Br J Dermatol 2007; 157:649-55. 2. Gisondi P, Tessari G, Conti A, Piaserico S, Schianchi S, Peserico A, et al. Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based case-control study. Br J Dermatol 2007;157:68-73. 3. Gisondi P, Targher G, Zoppini G, Girolomoni G. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol 2009;51:758-64.
4. Mehta NN, Yu Y, Pinnelas R, Krishnamoorthy P, Shin DB, Troxel AB, et al. Attributable risk estimate of severe psoriasis on major cardiovascular events. Am J Med 2011;124:775.e1-6. 5. Ahlehoff O, Gislason GH, Charlot M, Jørgensen CH, Lindhardsen J, Olesen JB, et al. Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. J Intern Med 2011;270:147-57. 6. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008;359:1811-21. 7. Zoppini G, Targher G, Bonora E. The role of serum uric acid in cardiovascular disease in type 2 diabetic and non-diabetic subjects: a narrative review. J Endocrinol Invest 2011;34: 881-6. 8. Kwon HH, Kwon IH, Choi JW, Youn JI. Cross-sectional study on the correlation of serum uric acid with disease severity in Korean patients with psoriasis. Clin Exp Dermatol 2011;36:473-8. 9. Isha, Jain VK, Lal H. C-reactive protein and uric acid levels in patients with psoriasis. Indian J Clin Biochem 2011;26:309-11. 10. Lea WA Jr, Curtis AC, Bernstein IA. Serum uric acid levels in psoriasis. J Invest Dermatol 1958;31:269-71. 11. Scott JT, Stodell MA. Serum uric acid levels in psoriasis. Adv Exp Med Biol 1984;165:283-5. 12. Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30:1212-8. 13. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006;54:2665-73. 14. National Cholesterol Education Program. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001;285:2486-97. 15. L opez-Reyes A, Hernandez-Dıaz C, Hofmann F, Pineda C. Gout mimicking psoriatic arthritis flare. J Clin Rheumatol 2012;18: 220. 16. Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Gomez-Acebo I, Miranda-Filloy JA, Paz-Carreira J, et al. Asymptomatic hyperuricemia and serum uric acid concentration correlate with subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease. Semin Arthritis Rheum 2009;39:157-62. 17. Wei L, Mackenzie IS, Chen Y, Struthers AD, MacDonald TM. Impact of allopurinol use on urate concentration and cardiovascular outcome. Br J Clin Pharmacol 2011;71:600-7.
P
soriasis is a chronic inflammatory disease that is often associated with features of the metabolic syndrome, including obesity, dyslipidemia, and type 2 diabetes.1-3 Psoriasis is also linked to an increased risk of incident cardiovascular disease (CVD).4,5 Similarly to psoriasis, growing epidemiologic evidence suggests that elevated levels of serum uric acid (SUA) are strongly associated with features of the metabolic syndrome and predict increased risk of CVD mortality and morbidity.6,7 Few studies have examined the relationship between psoriasis and hyperuricemia and their results have been inconclusive as most of these studies did not take into account the confounding effects of coexisting features of the metabolic syndrome.8-11 The aim of this study was to compare circulating levels of SUA and the prevalence of
From the Department of Medicine, Section of Dermatology,a and Section of Endocrinology, Diabetes, and Metabolism,b University of Verona. Supported by the Ministero della Salute, and the Ministero dell’Istruzione, Universita e Ricerca Scientifica (Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale), and by the Association for Dermatological Research. Conflicts of interest: None declared. Accepted for publication September 6, 2013. Reprints not available from the authors.
Abbreviations used: BMI: CVD: PASI: PsA: SUA:
body mass index cardiovascular disease Psoriasis Area and Severity Index psoriatic arthritis serum uric acid
hyperuricemia between psoriatic patients and control subjects.
METHODS Participants We enrolled 119 psoriatic patients, who consecutively attended our joined dermatology and rheumatology outpatient clinic, specifically dedicated to Correspondence to: Paolo Gisondi, MD, Department of Medicine, Section of Dermatology and Venereology, University of Verona, Piazzale Stefani 1, I-37126 Verona, Italy. E-mail: paolo.gisondi@ univr.it. Published online November 1, 2013. 0190-9622/$36.00 Ó 2013 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2013.09.005
127
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psoriasis and psoriatic arthritis (PsA), during the 126 mg/dL, hypoglycemic treatment, or both. period from January to June 2012. We included all Hypertriglyceridemia and hypercholesterolemia patients with a clinical diagnosis of psoriasis (ie, were defined as serum triglycerides 150 mg/dL or lasting at least 6 months) who either were never greater and total cholesterol 240 mg/dL or greater, or treated or stopped their systemic antipsoriatic treatlipid-lowering treatment. Metabolic syndrome was ments at least 3 months before the investigation. defined according to the widely used criteria proPatients with excessive alcohol consumption, adposed by the Adult Treatment Panel-III definition.14 vanced chronic kidney disHyperuricemia was defined ease, and those who were as a SUA level 7 mg/dL or CAPSULE SUMMARY taking any medications higher in men and 6 mg/dL known to affect SUA level or higher in women or alloPsoriasis is closely associated with (except for allopurinol), inpurinol use. features of the metabolic syndrome, cluding diuretics, salicylates, which may favor the development of ketoconazole, theophylline, Statistical analysis hyperuricemia. pyrazinamide, and ethambuData are presented as Hyperuricemia predisposes patients to tol, were not included in the means 6 SD or percentages. gouty arthritis and is now considered as study, as per study protocol. Statistical analyses included an emerging risk factor for Information on daily alcohol the paired t test for means cardiovascular mortality and morbidity. consumption was obtained and McNemar test for profrom all participants by a portions because the 2 The prevalence of hyperuricemia is standardized questiongroups were matched. A mulremarkably greater in psoriatic patients naire.12 In particular, alcohol tivariable logistic regression than in age-, sex-, and weight-matched consumption was assessed analysis was performed to control subjects, and is independent of on the basis of the selfidentify the factors that were coexisting metabolic disorders. reported number of drinks independently associated consumed per day. The folwith hyperuricemia. Two lowing amounts of alcoholic beverages were considforced-entry multivariable regression models were ered 1 drink: 330 mL of beer (containing ;5% performed: a model adjusted for age, sex, psoriasis, alcohol), 150 mL of wine (containing ;12% alcohol), and metabolic syndrome (model 1); and a model and 40 mL of strong spirits (containing ;50% alcoadjusted for age, sex, psoriasis, and individual comhol). Overall, most of our psoriatic patients were ponents of metabolic syndrome (model 2). All analabstainers or drank only minimally ( # 2 drinks per yses were performed using a statistical package (SPSS day; n = 83; 69.8%), whereas 30.2% of them drank 3 to 19.0, IBM Corp, Armonk, NY) and statistical signifi4 drinks per day. No participants drank more than 4 cance was assessed at the 2-tailed .05 thresholds. drinks per day. Each patient was visited either by a dermatologist and a rheumatologist who assessed the RESULTS presence/absence of PsA using Classification Criteria Clinical characteristics of participants are shown in for Psoriatic Arthritis (CASPAR) criteria13 and/or gout. Table I. By study design, age, sex, and BMI were Diagnosis of psoriasis was clinical, and disease almost identical between psoriatic patients and conseverity was scored using the Psoriasis Area and trol subjects. Psoriatic patients were more likely to Severity Index (PASI). The control group consisted of have metabolic syndrome, hypertension, type 2 dia119 adult individuals, who were randomly selected in betes, and hypertriglyceridemia whereas smoking and a 1:1 ratio among a historical cohort of 756 nonhypercholesterolemia were not significantly different psoriatic subjects to be matched for age, sex, and between the 2 groups. Notably, psoriatic patients had body mass index (BMI) to psoriatic patients. significantly higher levels of SUA than control subjects. As shown in Fig 1, the prevalence of hyperuricemia was remarkably greater in psoriatic patients than in Clinical and laboratory variables control subjects. Results remained essentially unVenous blood was withdrawn in the morning changed even when those with established diabetes after an overnight fast. SUA and other biochemical (n = 26), PsA (n = 75), or both were excluded from blood measurements were determined by standard analysis or when participants were stratified by sex. laboratory procedures. Obesity was defined as BMI Also in this case, men and women with psoriasis had 30 kg/m2 or higher. Hypertension was defined as significantly higher SUA than their counterparts withblood pressure greater than or equal to 140/90 mm out the skin disease (6.01 6 1.6 vs 5.20 6 1.4 mg/dL in Hg or hypertension treatment. Diabetes was men and 4.47 6 1.4 vs 3.85 6 1.0 mg/dL in women). defined as fasting glycemia greater than or equal to d
d
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Table I. Main clinical characteristics of the study participants
Clinical characteristics
Sex, M/F Age, y BMI, kg/m2 Obesity, n (%) Current smokers, n (%) Hypertension, n (%) Type 2 diabetes, n (%) Hypercholesterolemia, n (%) Hypertriglyceridemia, n (%) Metabolic syndrome, n (%) Serum uric acid, mg/dL Serum creatinine, mg/dL Psoriasis duration, y PASI score No. of previous treatments for psoriasis, n PsA, n (%)
Psoriatic patients (n = 119)
Control subjects (n = 119)
P value
88/31 54.1 6 12 27.8 6 4.6 36 (30.2) 20 (16.8) 61 (51.3) 21 (17.6) 15 (12.6)
88/31 54.3 6 8 27.8 6 3.1 35 (29.4) 18 (15.1) 45 (37.8) 5 (4.2) 17 (14.3)
Matched Matched Matched Matched .81 \.01 \.001 .76
27 (22.7)
21 (17.6)
.06
40 (33.6)
26 (21.8)
\.01
5.61 6 1.6 4.87 6 1.4 \.001 0.92 6 0.2 0.89 6 0.2 .86 21.3 6 13 NA 11.2 6 9 NA 1.7 6 0.7 NA
75 (63.0)
NA
Data are presented as means 6 SD or percentages. Differences are tested by the unpaired t test or the x 2 test (for categorical variables). BMI, Body mass index; F, female; M, male; NA, not applicable; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis.
Fig 2. Serum uric acid levels in psoriatic patients and control subjects stratified by status of the metabolic syndrome (MetS ). * and **P \.001 for difference between the 2 groups. *Refers to the difference between psoriatic patients and controls among the group with the metabolic syndrome. **Refers to the difference between psoriatic patients and controls among the group without the metabolic syndrome.
categorical variable), independently of each other, were significant predictors of hyperuricemia. Interestingly, among psoriatic patients, SUA levels were significantly higher in patients with PASI score 10 or greater than in those with PASI score less than 10 (SUA: 5.9 6 1.6 vs 5.2 6 1.5 mg/dL; P \ .05). In addition, SUA was positively associated with BMI (r = 0.34; P \.001), serum triglyceride (r = 0.24; P \.01), and creatinine levels (r = 0.33; P \ .001), but it was not significantly associated with age, sex, and psoriasis duration (data not shown). Finally, no significant difference was found in SUA levels between patients with PsA and those with psoriasis alone (SUA: 5.6 6 1.6 vs 5.5 6 1.5 mg/dL; P = .60).
DISCUSSION
Fig 1. Prevalence of hyperuricemia in psoriatic patients and in age-, sex-, and body mass indexematched control subjects. *P \ .001 for difference between the 2 groups.
Similarly, results remained unchanged when participants were stratified by the presence of metabolic syndrome; psoriatic patients, irrespective of the presence of metabolic syndrome, had significantly higher SUA levels than control subjects (Fig 2). Notably, as shown in Table II, multivariable logistic regression analysis revealed that both psoriasis and metabolic syndrome (included as
In this case-control study, we found that the prevalence of asymptomatic hyperuricemia was approximately 3-fold higher in psoriatic patients than in matched control subjects (19% vs 7%). Interestingly, and more importantly, the multivariable regression analysis showed that psoriasis was the strongest predictor of hyperuricemia after adjusting for potential confounders, such as age, sex, BMI, and other features of metabolic syndrome. Although hyperuricemia in psoriatic patients could be simply a consequence of obesity and other coexisting metabolic disorders,1,6,7 our findings suggest that psoriasis itself might, at least in part, contribute directly to hyperuricemia. Kwon et al8 recently proposed that an increased epidermal cell turnover could be an important cause of raised SUA levels among psoriatic patients. Our findings of a significant, graded relationship between SUA levels
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Table II. Predictors of hyperuricemia in the whole sample of participants: multivariable logistic regression models Clinical characteristics
Age, y Sex, M vs F Psoriasis, yes vs no Metabolic syndrome, yes vs no BMI, kg/m2 Type 2 diabetes, yes vs no Hypertension, yes vs no Hypertriglyceridemia, yes vs no
Multivariable model 1
P value
Multivariable model 2
P value
1.04 (0.98-1.08) 2.16 (0.77-6.84) 3.15 (1.28-7.61) 2.24 (1.14-4.96) Not included Not included Not included Not included
.20 .18 \.01 \.05 -
1.03 (0.98-1.07) 2.19 (0.74-6.82) 3.20 (1.31-7.58) Not included 1.10 (0.98-1.22) 0.87 (0.33-2.75) 1.54 (0.66-3.70) 1.73 (0.94-2.86)
.26 .17 \.01 .14 .73 .36 .19
Sample size, n = 238. Results are expressed as odds ratio and 95% confidence intervals. Covariates included in the 2 multivariable regression models were as follows: model 1 = age, sex, presence of psoriasis, and metabolic syndrome; model 2 = age, sex, presence of psoriasis, BMI, type 2 diabetes mellitus, hypertension, and hypertriglyceridemia. BMI, Body mass index; F, female; M, male.
and PASI further support this conclusion. However, additional research is required to uncover other specific mechanisms by which psoriasis might contribute to the development of hyperuricemia (possibly through increased uric acid production, decreased urinary uric acid excretion, or both). Our findings may have important clinical implications. Elevated SUA causes gouty arthritis, which needs to be differentiated from PsA in clinical practice.15 In addition, elevated SUA is associated with increased carotid-artery intima-media thickness in patients with PsA,16 and independently predicts the development of both CVD events and mortality in nonpsoriatic populations.6,7 Although the crosssectional design of this study does not allow us to draw any conclusion about a causal relationship between psoriasis and hyperuricemia, we believe that SUA levels should be routinely measured in psoriatic patients, and that the pharmacologic treatment of asymptomatic hyperuricemia might also be clinically relevant to the global treatment of patients. In a cohort study of approximately 7000 individuals aged 60 years or older, the treatment of hyperuricemia with higher doses of allopurinol was significantly associated with lower risks of both CVD events and mortality.17 However, whether this could be also applied to psoriatic patients needs to be investigated in future large intervention clinical trials. REFERENCES 1. Sterry W, Strober BE, Menter A. Obesity in psoriasis: the metabolic, clinical and therapeutic implications: report of an interdisciplinary conference and review. Br J Dermatol 2007; 157:649-55. 2. Gisondi P, Tessari G, Conti A, Piaserico S, Schianchi S, Peserico A, et al. Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based case-control study. Br J Dermatol 2007;157:68-73. 3. Gisondi P, Targher G, Zoppini G, Girolomoni G. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol 2009;51:758-64.
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