Hyperuricemia - Gout

  • Diagnosis
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Swollen, erythematous joint(s)

Criteria for Diagnosis

  • Diagnosis based on new guidelines (ACR/EULAR, 2015)
    • Step 1: Sufficient criterion (if met, can classify as gout)
      • Presence of MSU crystals in a symptomatic joint or bursa (i.e., in synovial fluid) or tophus
    • Step 2: The ACR/EULAR gout classification criteria
      • Entry criterion – at least 1 episode of swelling, pain, or tenderness in a peripheral joint or bursa
      • Score of 8 confirms gout

Laboratory Testing

  • Synovial fluid examination
    • Essential if main differential diagnosis is between gout and septic joint – otherwise not used very often
    • Cell count – predominance of polymorphonuclear cells
      • Absolute WBC cell count usually <50,000
    • Crystals – presence of uric acid crystals in fluid as viewed by polarized light microscopy is diagnostic
    • Gram stain and culture to rule out septic arthritis
  • Serum uric acid
    • Elevated in only 50% of patients during an acute attack
      • Lack of elevation does not rule out gout
    • Ideally measured >4 weeks after an acute attack
      • Repeat when joint normalizes if normal value found during an attack
    • Ideal method – uricase (ACR/EULAR, 2015)
  • CBC – modest leukocytosis may be present
    • Significant leukocytosis suggests septic joint
  • BUN and creatinine – to evaluate renal function
    • Drugs used to treat acute and chronic gout may affect renal function

Imaging Studies

  •  Acute gout – not useful
  • Chronic gout – may demonstrate tophi; erosive joint disease

Differential Diagnosis

  • Therapeutic goals are usually based on initial uric acid levels with attempts to normalize (<6 mg/dL)

Gout is a type of arthritis caused by hyperuricemia leading to deposits of monosodium urate crystals in tissues and joints.

Epidemiology

  • Prevalence – 3.9% in U.S. (ACR/EULAR, 2015)
  • Age – unusual <30 years; peaks at 12% >80 years
  • Sex – M>F; 4-9:1

Risk Factors

  • Obesity (BMI ≥30 kg/m2)
  • Diuretic therapy (loop diuretics have highest risk)
  • Diet high in fructose corn syrup (eg, sweetened beverages)
  • High purine diet (red meat, wild game, or organ meats)
    • Nuts, oats, asparagus, legumes are high in purine but don’t seem to increase risk
  • Alcohol consumption  (particularly beer)
  • Male sex
  • Common acute attack triggers in patients with preestablished gout
    • Trauma
    • Surgery
    • Psoriasis exacerbation
    • Diuresis
    • Starting or stopping allopurinol
    • Infections

Pathophysiology

  • Uric acid – final byproduct of purine metabolism; poorly soluble
  • Hyperuricemia – often caused by altered purine metabolism, leads to increased levels of uratic acid
    • Decreased excretion, increased production, or a combination of factors may be involved as etiology of hyperuricemia
    • When solubility limits are exceeded, monosodium urate crystals precipitate in joints, kidneys, and soft tissues
      • Crystal deposition triggers immune activation with release of inflammatory cytokines and neutrophils
      • Tophi – monosodium urate crystals in a matrix of lipids, protein, and mucopolysaccharides

Clinical Presentation

  • Typically a clinical diagnosis
  • Nonspecific – fever
  • Monoarticular arthritis
    • More common in lower extremities – typical joints include first metatarsophalangeal, midfoot, ankle
  • Pain, erythema, and swelling of joint
    • Abrupt onset
    • Usually takes <24 hours to go from asymptomatic to maximum pain
    • Complete remission between episodes
    • Resolution of symptoms usually ≤14 days
  • May cause fever, leukocytosis, and/or cellulitis over joint
  • Chronic gout
    • Tophi – subcutaneous nodules
      • Typical locations – joints, ears, finger pads, olecranon bursa
    • Joint erosion and destruction
      • Typically visible on x-ray of affected joint
    • Increased susceptibility to septic joints – knee and olecranon bursa most common
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Cell Count, Body Fluid 0095019
Method: Cell Count/Differential

Gram Stain 0060101
Method: Stain/Microscopy

Body Fluid Culture and Gram Stain 0060108
Method: Stain/Culture/Identification

Limitations 

Anaerobe culture is NOT included with this order

Uric Acid, Serum or Plasma 0020026
Method: Quantitative Spectrophotometry

Limitations 

Lack of elevation does not rule out gout (may also be normal during acute attack)

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite) but only when concentrations are at or above those expected during acetaminophen overdose

Follow-up 

If normal when performed during acute attack, repeat testing when joint normalizes

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Guidelines

Neogi T, Jansen TL, Dalbeth N, Fransen J, Schumacher HR, Berendsen D, Brown M, Choi H, Edwards NL, Janssens HJ, Lioté F, Naden RP, Nuki G, Ogdie A, Perez-Ruiz F, Saag K, Singh JA, Sundy JS, Tausche AK, Vaquez-Mellado J, Yarows SA, Taylor WJ. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2015 Oct;74(10):1789-98.

Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yü TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977; 20(3): 895-900. PubMed

Zhang W, Doherty M, Pascual E, Bardin T, Barskova V, Conaghan P, Gerster J, Jacobs J, Leeb B, Lioté F, McCarthy G, Netter P, Nuki G, Perez-Ruiz F, Pignone A, Pimentão J, Punzi L, Roddy E, Uhlig T, Zimmermann-Gòrska I, EULAR Standing Committee for International Clinical Studies Including Therapeutics. 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(10): 1301-11. PubMed

General References

Courtney P, Doherty M. Joint aspiration and injection and synovial fluid analysis. Best Pract Res Clin Rheumatol. 2009; 23(2): 161-92. PubMed

Eggebeen AT. Gout: an update. Am Fam Physician. 2007; 76(6): 801-8. PubMed

Hainer BL, Matheson E, Wilkes T. Diagnosis, treatment, and prevention of gout. Am Fam Physician. 2014; 90(12): 831-6. PubMed

Lillicrap M. Crystal arthritis: contemporary approaches to diseases of antiquity. Clin Med. 2007; 7(1): 60-4. PubMed

Mandell BF. Clinical manifestations of hyperuricemia and gout. Cleve Clin J Med. 2008; 75 Suppl 5: S5-8. PubMed

Minisola S, Pepe J, Piemonte S, Cipriani C. The diagnosis and management of hypercalcaemia. BMJ. 2015; 350: h2723. PubMed

Pascual E, Sivera F, Andrés M. Synovial fluid analysis for crystals. Curr Opin Rheumatol. 2011; 23(2): 161-9. PubMed

Underwood M. Diagnosis and management of gout. BMJ. 2006; 332(7553): 1315-9. PubMed

Medical Reviewers

Last Update: August 2016