Hyperuricemia - Gout

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

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

Indications for Testing

  • Swollen, erythematous joint(s)

Criteria for Diagnosis

  • Diagnosis based on the American College of Radiology/European League against Rheumatism (ACR/EULAR) 2015 guidelines
    • Step 1: sufficient criterion (if met, can classify as gout)
      • Presence of tophus – monosodium urate (MSU) crystals in a symptomatic joint or bursa (ie, in synovial fluid)
    • Step 2: ACR/EULAR gout classification criteria
      • Entry criterion – ≥1 episode of swelling, pain, or tenderness in a peripheral joint or bursa
      • Score of 8 confirms gout

Laboratory Testing

  • 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
      • If normal value found during an attack, repeat when joint normalizes
    • Ideal method – uricase (ACR/EULAR, 2015)
  • 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 white blood cell (WBC) 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
  • CBC – modest leukocytosis may be present
    • Significant leukocytosis suggests septic joint
  • Blood urea nitrogen (BUN) and creatinine – to evaluate renal function
    • Drugs used to treat acute and chronic gout may be affected by renal function
      • Uricosuric drugs less effective; other drugs need dosing modifications
  • HLA-B*5801 testing (not currently available at ARUP Laboratories)
    • Prior to initiation of allopurinol, consider polymerase chain reaction (PCR) based testing for HLA-B*5801 in high-risk populations due to increased risk for life-threatening hypersensitivity reaction with allopurinol (ACR, 2012)
      • Koreans with stage 3 or worse chronic kidney disease (CKD)
      •  All those of Han Chinese and Thai descent

Imaging Studies

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

Differential Diagnosis

  • Calcium pyrophosphate dihydrate disease (pseudogout)
  • Reactive arthritis (eg, Campylobacter jejuni)
  • Septic arthritis
  • Cellulitis
  • Osteoarthritis
  • Rheumatoid arthritis, other arthritides
  • Internal ligament derangement
  • Hemarthropathy
  • Traumatic arthritis
  • Serum urate should  be lowered to improve signs and symptoms of gout, with a minimum target of 6 mg/dL, and often <5 mg/dL (American College of Radiology [ACR], 2012; European League against Rheumatism [EULAR], 2016)
  • Current evidence is not sufficient to recommend a goal serum uric acid level in terms of the benefits of higher dosing versus the harms of higher doses (American College of Physicians [ACP],  2017)
  • Evidence does support a decreased number of gout flares with preventative dosing below a serum urate level of 7 mg/dL, although the benefits are not seen for 6 months (ACP,  2017)
  • Serum uric acid level ≤3 mg/dL not recommended for long-term treatment (EULAR, 2016)

Epidemiology

  • Prevalence – 3.9% in U.S. (American College of Radiology/European League against Rheumatism [ACR/EULAR], 2015)
  • Age – unusual <30 years; peaks at 12% >80 years
  • Sex – M>F; 4-9:1

Risk Factors

  • Obesity (body mass index [BMI] ≥30 kg/m2)
  • Medications – thiazide and loop diuretics, niacin, and calcineurin inhibitors
  • 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 do not seem to increase risk
  • Alcohol consumption (particularly beer)
  • Male sex
  • Poor kidney function
  • 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, MSU crystals precipitate in joints, kidneys, and soft tissues
      • Crystal deposition triggers immune activation with release of inflammatory cytokines and neutrophils
      • Tophi – MSU 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.

Uric Acid, Serum or Plasma 0020026
Method: Quantitative Spectrophotometry

Limitations 

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

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

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.

Qaseem A, McLean RM, Starkey M, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017; 166(1): 52-57. PubMed

Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castañeda-Sanabria J, Coyfish M, Guillo S, Jansen TL, Janssens H, Lioté F, Mallen C, Nuki G, Perez-Ruiz F, Pimentão J, Punzi L, Pywell T, So A, Tausche AK, Uhlig T, Zavada J, Zhang W, Tubach F, Bardin T. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017; 76(1): 29-42. PubMed

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

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

Content Reviewed: 
May 2017

Last Update: October 2017