eMedicine Specialties > Rheumatology > Crystal-Induced Arthritis

Gout: Differential Diagnoses & Workup

Author: Anne V Miller, MD, Assistant Professor of Medicine, Division of Rheumatology, Southern Illinois University School of Medicine
Coauthor(s): Sriya K M Ranatunga, MD, MPH,, Assistant Professor, Department of Clinical Medicine, Southern Illinois University School of Medicine; Mark L Francis, MD, Chief, Associate Professor, Department of Internal Medicine, Division of Rheumatology, Southern Illinois University School of Medicine
Contributor Information and Disclosures

Updated: Feb 20, 2009

Differential Diagnoses

Other Problems to Be Considered

Hypoxanthine-guanine phosphoribosyltransferase deficiency (Lesch-Nyhan syndrome)
Phosphoribosylpyrophosphate synthetase superactivity
Congenital fructose intolerance

Workup

Laboratory Studies

• Synovial fluid: When a patient presents with acute inflammatory monoarticular arthritis, aspiration of the involved joint is critical to rule out an infectious arthritis and to attempt to confirm a diagnosis of gout or pseudogout based on identification of crystals.
  
  

  

  Gout. Fluid obtained from a tophaceous deposit in a patient with gout.

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  Gout. Fluid obtained from a tophaceous deposit in a patient with gout.

  • The critical and essential study is synovial fluid analysis to identify urate crystals. Finding intracellular urate crystals with polarizing light microscopy firmly establishes the diagnosis of gouty arthritis.
  • Urate crystals are shaped like needles or toothpicks with pointed ends.
    
    

    

    Gout. Needles of urate on polarizing microscopy.

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    Gout. Needles of urate on polarizing microscopy.

  • Urate crystals are negatively birefringent, meaning that the crystals are yellow when aligned parallel to the slow ray of the compensator and that they are blue when they are perpendicular.
    
    

    

    Gout. Strongly negative birefringent, needle-shaped crystals diagnostic of gout obtained from an acutely inflamed joint.

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    Gout. Strongly negative birefringent, needle-shaped crystals diagnostic of gout obtained from an acutely inflamed joint.

  • Pseudogout crystals (calcium pyrophosphate) are rod-shaped with blunt ends.
  • Pseudogout crystals are positively birefringent. Pragmatically, this means that their colors are opposite those of gout. Thus, pseudogout crystals are blue when aligned parallel to the slow ray of the compensator and yellow when they are perpendicular.
  • Crystals need to be distinguished from birefringent cartilaginous or other debris. Debris may have fuzzy borders and may be curved, whereas crystals have sharp borders and are straight.
  • Corticosteroids injected into joints have a crystalline structure that can mimic monosodium urate crystals. They can be either positively or negatively birefringent.
  • The sensitivity of a synovial fluid analysis for crystals is 84%, with a specificity of 100%. If gout remains a clinical consideration after negative analysis findings, the procedure can be repeated in another joint or with a subsequent flare. Crystals may be absent very early in a flare.
  • While the sensitivity is inferior, urate crystals can be identified from synovial fluid aspirated from previously inflamed joints that are not currently inflamed. Such crystals are generally extracellular.
  • Minute quantities of fluid in the shaft or hub of the needle are sufficient for synovial fluid analysis.
  • Once a diagnosis of gout is established based on confirmation of crystals, joints do not need repeat aspiration with subsequent flares unless infection is suggested or the flare does not respond appropriately to therapy for acute gout.
  • In patients with acute monoarticular arthritis, send synovial fluid for Gram stain and culture and sensitivity. The culture also provides sensitivities for antibiotic management.
  • Synovial fluid should also be sent for cell count.
  • During acute attacks, the synovial fluid is inflammatory, with a WBC count greater than 2000/µL (class II fluid) and possibly greater than 50,000/µL, with a predominance of polymorphonuclear neutrophils.
  • Synovial fluid glucose levels are usually normal, whereas they may be depressed in septic arthritis and occasionally in rheumatoid arthritis. Measurement of synovial fluid protein has no clinical value.
  • Crystalline arthritis and infectious arthritis can coexist. Indeed, infectious arthritis is more common in previously damaged joints, which may occur in patients with chronic gouty arthritis.
• Serum uric acid
  • This is the most misused test in the diagnosis of gout. The presence of hyperuricemia in the absence of symptoms is not diagnostic of gout. In addition, as many as 10% of patients with symptoms due to gout may have normal serum uric acid levels at the time of their attack. Thus, the correct diagnosis of gout can be missed if the joint is not aspirated. Remember that situations that decrease uric acid levels can trigger attacks of gout. In such cases, the patient's prior medical records may reveal prior elevations of uric acid.
  • Five to eight percent of the population has elevated serum uric acid levels (>7 mg/dL), but only 5-20% of patients with hyperuricemia develop gout. Thus, an elevated serum uric acid level does not indicate or predict gout. As noted above, gout is diagnosed based on the discovery of urate crystals in the synovial fluid or soft tissues. More importantly, some patients with infectious arthritis present with a hot swollen joint and an elevated serum uric acid level and are at risk of being mismanaged if their synovial fluid is not aspirated to rule out septic arthritis.
  • Asymptomatic hyperuricemia should generally not be treated. However, patients with levels higher than 11 mg/dL and overexcretion of uric acid are at risk for renal stones and renal impairment; therefore, renal function should be monitored in these individuals.¹⁵
  • The level of serum uric acid correlates with risk for developing gout. The 5-year risk for developing gout is approximately 0.6% if the level is less than 7.9 mg/dL, 1% if 8-8.9 mg/dL, and 22% if higher than 9 mg/dL.
• Uric acid in 24-hour urine sample
  • A 24-hour urinary uric acid evaluation is generally performed if uricosuric therapy is being considered.
  • If patients excrete more than 800 mg of uric acid in 24 hours on a regular diet, they are overexcretors and thus overproducers of uric acid. These patients (approximately 10% of patients with gout) require allopurinol instead of probenecid to reduce uric acid levels.
  • Patients who excrete more than 1100 mg in 24 hours should undergo close renal function monitoring because of the risk of stones and urate nephropathy.
  • In patients in whom probenecid is contraindicated (eg, those with a history of renal stones or renal insufficiency), a 24-hour urine test of uric acid excretion does not need to be performed because the patient clearly will need allopurinol.
• Blood chemistry
  • Obtaining an accurate measure of the patient's renal function before deciding on therapy for gout is important, since the serum creatinine evaluation alone can underestimate renal dysfunction in elderly patients or in patients with low muscle mass.
  • Patients with gout are at an increased risk of developing diabetes mellitus.
  • Abnormal liver function tests need to be considered when therapy is selected.
• CBC count: The WBC count may be elevated in patients during the acute gouty attack, particularly if it is polyarticular.
• Lipids: Hypertriglyceridemia and low high-density lipoproteins are associated with gout.
• Urinalysis: Patients with gout are at an increased risk of renal stones; therefore, these patients may have a history of hematuria.

Imaging Studies

• Radiography
  • Plain radiographs may show findings consistent with gout, but these findings are not diagnostic. The most common radiographic findings early in the disease include soft-tissue swelling or an absence of abnormalities.
  • Haziness suggestive of tophi can be seen in late gout, and tophi may calcify.
  • Erosions that are not typical of rheumatoid arthritis may suggest gout.
    • Erosions with maintenance of the joint space
    • Erosions without periarticular osteopenia
    • Erosions outside the joint capsule
    • Erosions with overhanging edges
      
      

      

      Gout. Radiograph of erosions with overhanging edges.

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      Gout. Radiograph of erosions with overhanging edges.

    • Erosions with sclerotic borders, sometimes called cookie-cutter or punched-out borders
    • Erosions that are distributed asymmetrically among the joints, with strong predilection for distal joints, especially in the lower extremities
      
      

      

      Gout. Plain radiograph showing typical changes of gout in the first metatarsophalangeal joint and fourth interphalangeal joint.

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      Gout. Plain radiograph showing typical changes of gout in the first metatarsophalangeal joint and fourth interphalangeal joint.

      
      
      

      

      Gout. Plain radiograph showing chronic tophaceous gouty arthritis in the hands.

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      Gout. Plain radiograph showing chronic tophaceous gouty arthritis in the hands.

Procedures

Perform arthrocentesis to rule out an infectious arthritis and to establish a crystal-proven diagnosis of gout. Tophi also may be aspirated for crystal analysis under polarizing microscopy.

Histologic Findings

Tophi have been found in all tissues except the brain. However, monosodium urate dissolves in formalin; therefore, only the ghosts of urate crystals may be seen if formalin is used. Alcohol-fixed tissue is best for identification of urate crystals.

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