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Are serum uric acid levels always elevated in acute gout?
NO. Many patients with acute gout (11%-49%) have normal serum uric acid (SUA) levels (strength of recommendation [SOR]: A, prospective cohort studies). Patients taking allopurinol are significantly more likely to have normal uric acid levels during acute gout attacks (SOR: B, extrapolated from prospective cohorts).
Evidence summary
Six studies have evaluated SUA levels in patients with acute gout. Despite variations in diagnostic approach (clinical criteria vs synovial crystal analysis) and definitions of normal SUA (based on laboratory methods and sex), all 6 studies found normal levels in 11% to 49% of patients with acute gout (TABLE 1).
TABLE 1
Serum uric acid and acute gout: The evidence
| Type of cohort (n) | LOE* | Setting | Method of diagnosis | % with normal serum uric acid |
|---|---|---|---|---|
| Prospective1 (28) | 1b | Veterans Administration rheumatology clinic | Crystal positivity | 11% |
| Prospective2 (38) | 1b | Multiple settings (eg, inpatient, clinic, ED) | Clinical criteria or crystal positivity | 43% |
| Retrospective3 (226) | 2b | Hospitalized patients | Clinical criteria or crystal positivity | 12% |
| Retrospective4 (339) | 2b | Multiple settings | Crystal positivity | 32% |
| Retrospective5 (41) | 2b | Rheumatology clinic | Clinical criteria | 49% |
| Retrospective6 (69) | 2b | Multiple settings | Clinical criteria | 33%† |
| ED, emergency department; LOE, level of evidence. *1b, prospective cohort study with good follow-up (>80%); 2b, retrospective cohort study or prospective study with poor follow-up. †Not necessarily during acute gout. | ||||
Elevated SUA can be an indicator of gout—or not
A prospective cohort study of 82 patients at a Veterans Administration rheumatology clinic found elevated SUA to be the most sensitive indicator among various clinical criteria for diagnosing acute gout. However, 3 (11%) of the 28 patients who had crystal-proven gout also had a normal SUA.1
A second prospective cohort study that evaluated 38 patients during 42 episodes of acute gout in various clinical settings reported a normal SUA in 43% of patients diagnosed on clinical grounds or by joint aspiration.2
Some patients become hyperuricemic after diagnosis
The largest retrospective cohort study evaluated 226 Korean inpatients with acute gout diagnosed either by synovial crystals or American College of Rheumatology (ACR) criteria (TABLE 2). It found that 12% (27) had a normal SUA at diagnosis. Interestingly, 81% became hyperuricemic some time after diagnosis.3
TABLE 2
American College of Rheumatology criteria for classifying acute gouty arthritis
|
| Source: Wallace SL et al. Arthritis Rheum. 1977.7 |
What is a normal SUA value?
Another study reviewed SUA levels in a cohort derived from 2 large prospective RCTs of etoricoxib in patients diagnosed with acute gout by crystal analysis. The proportion of patients with a normal SUA varied substantially according to the definition of a normal value: 32% were normal using a value of 0.48 mmol/L; 11% had normal SUA levels when 0.36 mmol/L was used as the cutoff.4
A secondary analysis evaluated the effect of allopurinol on SUA. The proportion of patients on allopurinol with a normal SUA level compared with patients not taking allopurinol was 49% vs 29% using the higher normal cutoff value, and 29% vs 11% using the lower normal value (P<.001).4
Two studies find many gout patients with a normal SUA
A Japanese retrospective cohort study using ACR criteria found that nearly half of patients diagnosed with acute gout had a normal SUA level.5 A 1967 retrospective examination of Framingham Heart Study data found that one-third of patients clinically diagnosed with gout had a normal level. Some of the patients hadn’t been diagnosed at the time their SUA was measured, however.6
Recommendations
The ACR’s 1977 criteria for diagnosing gout include hyperuricemia as one potential indicator.7 The European League Against Rheumatism advises that normal SUA levels may accompany crystal-proven gout because uric acid either acts as a negative acute-phase reactant or increases in renal excretion during acute episodes. They conclude that SUA has “limited diagnostic value,” especially during acute gout.8
1. Malik A, Schumacher HR, Dinnella JE, et al. Clinical diagnostic criteria for gout: comparison with the gold standard of synovial fluid crystal analysis. J Clin Rheumatol. 2009;15:22-24.
2. Logan JA, Morrison E, McGill PE. Serum uric acid in acute gout. Ann Rheum Dis. 1997;56:696-697.
3. Park YB, Park YS, Lee SC, et al. Clinical analysis of gouty patients with normouricaemia at diagnosis. Ann Rheum Dis. 2003;62:90-92.
4. Schlesinger N, Norquist JM, Watson DJ. Serum urate during acute gout. J Rheumatol. 2009;36:1287-1289.
5. Urano W, Yamanaka H, Tsutani H, et al. The inflammatory process in the mechanism of decreased serum uric acid concentrations during acute gouty arthritis. J Rheumatol. 2002;29:1950-1953.
6. Hall AP, Barry PE, Dawber TR, et al. Epidemiology of gout and hyperuricemia. A long-term population study. Am J Med. 1967;42:27-37.
7. Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977;20:895-900.
8. Zhang W, Doherty M, Pascual E, et al. EULAR evidence based recommendations for gout. Part I: diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006;65:1301-1311.
NO. Many patients with acute gout (11%-49%) have normal serum uric acid (SUA) levels (strength of recommendation [SOR]: A, prospective cohort studies). Patients taking allopurinol are significantly more likely to have normal uric acid levels during acute gout attacks (SOR: B, extrapolated from prospective cohorts).
Evidence summary
Six studies have evaluated SUA levels in patients with acute gout. Despite variations in diagnostic approach (clinical criteria vs synovial crystal analysis) and definitions of normal SUA (based on laboratory methods and sex), all 6 studies found normal levels in 11% to 49% of patients with acute gout (TABLE 1).
TABLE 1
Serum uric acid and acute gout: The evidence
| Type of cohort (n) | LOE* | Setting | Method of diagnosis | % with normal serum uric acid |
|---|---|---|---|---|
| Prospective1 (28) | 1b | Veterans Administration rheumatology clinic | Crystal positivity | 11% |
| Prospective2 (38) | 1b | Multiple settings (eg, inpatient, clinic, ED) | Clinical criteria or crystal positivity | 43% |
| Retrospective3 (226) | 2b | Hospitalized patients | Clinical criteria or crystal positivity | 12% |
| Retrospective4 (339) | 2b | Multiple settings | Crystal positivity | 32% |
| Retrospective5 (41) | 2b | Rheumatology clinic | Clinical criteria | 49% |
| Retrospective6 (69) | 2b | Multiple settings | Clinical criteria | 33%† |
| ED, emergency department; LOE, level of evidence. *1b, prospective cohort study with good follow-up (>80%); 2b, retrospective cohort study or prospective study with poor follow-up. †Not necessarily during acute gout. | ||||
Elevated SUA can be an indicator of gout—or not
A prospective cohort study of 82 patients at a Veterans Administration rheumatology clinic found elevated SUA to be the most sensitive indicator among various clinical criteria for diagnosing acute gout. However, 3 (11%) of the 28 patients who had crystal-proven gout also had a normal SUA.1
A second prospective cohort study that evaluated 38 patients during 42 episodes of acute gout in various clinical settings reported a normal SUA in 43% of patients diagnosed on clinical grounds or by joint aspiration.2
Some patients become hyperuricemic after diagnosis
The largest retrospective cohort study evaluated 226 Korean inpatients with acute gout diagnosed either by synovial crystals or American College of Rheumatology (ACR) criteria (TABLE 2). It found that 12% (27) had a normal SUA at diagnosis. Interestingly, 81% became hyperuricemic some time after diagnosis.3
TABLE 2
American College of Rheumatology criteria for classifying acute gouty arthritis
|
| Source: Wallace SL et al. Arthritis Rheum. 1977.7 |
What is a normal SUA value?
Another study reviewed SUA levels in a cohort derived from 2 large prospective RCTs of etoricoxib in patients diagnosed with acute gout by crystal analysis. The proportion of patients with a normal SUA varied substantially according to the definition of a normal value: 32% were normal using a value of 0.48 mmol/L; 11% had normal SUA levels when 0.36 mmol/L was used as the cutoff.4
A secondary analysis evaluated the effect of allopurinol on SUA. The proportion of patients on allopurinol with a normal SUA level compared with patients not taking allopurinol was 49% vs 29% using the higher normal cutoff value, and 29% vs 11% using the lower normal value (P<.001).4
Two studies find many gout patients with a normal SUA
A Japanese retrospective cohort study using ACR criteria found that nearly half of patients diagnosed with acute gout had a normal SUA level.5 A 1967 retrospective examination of Framingham Heart Study data found that one-third of patients clinically diagnosed with gout had a normal level. Some of the patients hadn’t been diagnosed at the time their SUA was measured, however.6
Recommendations
The ACR’s 1977 criteria for diagnosing gout include hyperuricemia as one potential indicator.7 The European League Against Rheumatism advises that normal SUA levels may accompany crystal-proven gout because uric acid either acts as a negative acute-phase reactant or increases in renal excretion during acute episodes. They conclude that SUA has “limited diagnostic value,” especially during acute gout.8
NO. Many patients with acute gout (11%-49%) have normal serum uric acid (SUA) levels (strength of recommendation [SOR]: A, prospective cohort studies). Patients taking allopurinol are significantly more likely to have normal uric acid levels during acute gout attacks (SOR: B, extrapolated from prospective cohorts).
Evidence summary
Six studies have evaluated SUA levels in patients with acute gout. Despite variations in diagnostic approach (clinical criteria vs synovial crystal analysis) and definitions of normal SUA (based on laboratory methods and sex), all 6 studies found normal levels in 11% to 49% of patients with acute gout (TABLE 1).
TABLE 1
Serum uric acid and acute gout: The evidence
| Type of cohort (n) | LOE* | Setting | Method of diagnosis | % with normal serum uric acid |
|---|---|---|---|---|
| Prospective1 (28) | 1b | Veterans Administration rheumatology clinic | Crystal positivity | 11% |
| Prospective2 (38) | 1b | Multiple settings (eg, inpatient, clinic, ED) | Clinical criteria or crystal positivity | 43% |
| Retrospective3 (226) | 2b | Hospitalized patients | Clinical criteria or crystal positivity | 12% |
| Retrospective4 (339) | 2b | Multiple settings | Crystal positivity | 32% |
| Retrospective5 (41) | 2b | Rheumatology clinic | Clinical criteria | 49% |
| Retrospective6 (69) | 2b | Multiple settings | Clinical criteria | 33%† |
| ED, emergency department; LOE, level of evidence. *1b, prospective cohort study with good follow-up (>80%); 2b, retrospective cohort study or prospective study with poor follow-up. †Not necessarily during acute gout. | ||||
Elevated SUA can be an indicator of gout—or not
A prospective cohort study of 82 patients at a Veterans Administration rheumatology clinic found elevated SUA to be the most sensitive indicator among various clinical criteria for diagnosing acute gout. However, 3 (11%) of the 28 patients who had crystal-proven gout also had a normal SUA.1
A second prospective cohort study that evaluated 38 patients during 42 episodes of acute gout in various clinical settings reported a normal SUA in 43% of patients diagnosed on clinical grounds or by joint aspiration.2
Some patients become hyperuricemic after diagnosis
The largest retrospective cohort study evaluated 226 Korean inpatients with acute gout diagnosed either by synovial crystals or American College of Rheumatology (ACR) criteria (TABLE 2). It found that 12% (27) had a normal SUA at diagnosis. Interestingly, 81% became hyperuricemic some time after diagnosis.3
TABLE 2
American College of Rheumatology criteria for classifying acute gouty arthritis
|
| Source: Wallace SL et al. Arthritis Rheum. 1977.7 |
What is a normal SUA value?
Another study reviewed SUA levels in a cohort derived from 2 large prospective RCTs of etoricoxib in patients diagnosed with acute gout by crystal analysis. The proportion of patients with a normal SUA varied substantially according to the definition of a normal value: 32% were normal using a value of 0.48 mmol/L; 11% had normal SUA levels when 0.36 mmol/L was used as the cutoff.4
A secondary analysis evaluated the effect of allopurinol on SUA. The proportion of patients on allopurinol with a normal SUA level compared with patients not taking allopurinol was 49% vs 29% using the higher normal cutoff value, and 29% vs 11% using the lower normal value (P<.001).4
Two studies find many gout patients with a normal SUA
A Japanese retrospective cohort study using ACR criteria found that nearly half of patients diagnosed with acute gout had a normal SUA level.5 A 1967 retrospective examination of Framingham Heart Study data found that one-third of patients clinically diagnosed with gout had a normal level. Some of the patients hadn’t been diagnosed at the time their SUA was measured, however.6
Recommendations
The ACR’s 1977 criteria for diagnosing gout include hyperuricemia as one potential indicator.7 The European League Against Rheumatism advises that normal SUA levels may accompany crystal-proven gout because uric acid either acts as a negative acute-phase reactant or increases in renal excretion during acute episodes. They conclude that SUA has “limited diagnostic value,” especially during acute gout.8
1. Malik A, Schumacher HR, Dinnella JE, et al. Clinical diagnostic criteria for gout: comparison with the gold standard of synovial fluid crystal analysis. J Clin Rheumatol. 2009;15:22-24.
2. Logan JA, Morrison E, McGill PE. Serum uric acid in acute gout. Ann Rheum Dis. 1997;56:696-697.
3. Park YB, Park YS, Lee SC, et al. Clinical analysis of gouty patients with normouricaemia at diagnosis. Ann Rheum Dis. 2003;62:90-92.
4. Schlesinger N, Norquist JM, Watson DJ. Serum urate during acute gout. J Rheumatol. 2009;36:1287-1289.
5. Urano W, Yamanaka H, Tsutani H, et al. The inflammatory process in the mechanism of decreased serum uric acid concentrations during acute gouty arthritis. J Rheumatol. 2002;29:1950-1953.
6. Hall AP, Barry PE, Dawber TR, et al. Epidemiology of gout and hyperuricemia. A long-term population study. Am J Med. 1967;42:27-37.
7. Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977;20:895-900.
8. Zhang W, Doherty M, Pascual E, et al. EULAR evidence based recommendations for gout. Part I: diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006;65:1301-1311.
1. Malik A, Schumacher HR, Dinnella JE, et al. Clinical diagnostic criteria for gout: comparison with the gold standard of synovial fluid crystal analysis. J Clin Rheumatol. 2009;15:22-24.
2. Logan JA, Morrison E, McGill PE. Serum uric acid in acute gout. Ann Rheum Dis. 1997;56:696-697.
3. Park YB, Park YS, Lee SC, et al. Clinical analysis of gouty patients with normouricaemia at diagnosis. Ann Rheum Dis. 2003;62:90-92.
4. Schlesinger N, Norquist JM, Watson DJ. Serum urate during acute gout. J Rheumatol. 2009;36:1287-1289.
5. Urano W, Yamanaka H, Tsutani H, et al. The inflammatory process in the mechanism of decreased serum uric acid concentrations during acute gouty arthritis. J Rheumatol. 2002;29:1950-1953.
6. Hall AP, Barry PE, Dawber TR, et al. Epidemiology of gout and hyperuricemia. A long-term population study. Am J Med. 1967;42:27-37.
7. Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977;20:895-900.
8. Zhang W, Doherty M, Pascual E, et al. EULAR evidence based recommendations for gout. Part I: diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006;65:1301-1311.
Evidence-based answers from the Family Physicians Inquiries Network