Gout

Gout is a type of inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in tissues and joints as a result of persistent hyperuricemia. The condition includes acute attacks of joint swelling and pain, followed by periods of remission. Progression to chronic gout may be accompanied by accumulation of MSU crystals, also called tophi, in joints or other soft tissue. Accurate gout diagnosis is important to ensure proper treatment and medical management; it is particularly important to differentiate gout from conditions such as rheumatoid arthritis and septic arthritis because treatment of these conditions differs. Detection of MSU crystals in synovial fluid aspirate remains the standard for definitive diagnosis; however, this technique is painful and often technically difficult. The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have developed a scoring system based on clinical and laboratory findings to aid in the diagnosis of gout.

Quick Answers for Clinicians

How does the presence of hyperuricemia inform gout diagnosis?

Hyperuricemia is a common condition and is classified by elevated serum urate concentrations. The most common complication of hyperuricemia is gout. However, many cases of hyperuricemia are asymptomatic. In patients with gout, serum urate concentrations are generally high, but can be normal at the time of an acute gout flare. The presence of hyperuricemia aids in the clinical diagnosis of gout, but it does not definitively confirm the diagnosis. Persistently low serum urate concentrations make the diagnosis of gout less likely. The Criteria for Diagnosis section has more detailed information about the definitive diagnosis of gout.

What is the role of imaging in the diagnosis of gout?

Imaging methods such as radiography and magnetic resonance imaging (MRI) may be useful in monitoring the progression of joint erosion or tophus size in chronic gout. Ultrasound and dual-energy computed tomography (DECT) are used to detect urate deposition in symptomatic joints. All of these imaging modalities are included in the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) gout classification criteria. Imaging alone is insufficient to definitively diagnose gout and should be used in addition to laboratory testing methods.

What is the difference between gout and pseudogout?

Gout is caused by deposition of monosodium urate (MSU) crystals in tissues and joints, whereas pseudogout is caused by calcium pyrophosphate crystal deposition. For this reason, pseudogout is formally called calcium pyrophosphate crystal deposition (CPPD) disease. The diagnosis of CPPD also involves synovial fluid and crystal analysis.

Indications for Testing

Laboratory testing for gout may be appropriate in people who have experienced at least one episode of peripheral joint or bursal swelling, pain, or tenderness. Definitive diagnosis of suspected gout is important to ensure proper treatment.

Criteria for Diagnosis

The ACR/EULAR gout classification criteria were developed to provide guidance for the diagnosis of gout. The entry criterion requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. If MSU crystals are present in the synovial fluid, a definitive diagnosis can be made. If the presence of MSU crystals cannot be confirmed, the scoring system below should be utilized. A threshold score of ≥8 is considered diagnostic for gout.

ACR/EULAR Gout Classification Criteria^a
Category	Criteria	Characteristic	Score
Clinical	Pattern of joint/bursa involvement during symptomatic episode(s) (ever)^b	Ankle or midfoot (as part of monoarticular or oligoarticular episode without involvement of the first metatarsophalangeal joint)	1
Clinical		Involvement of the first metatarsophalangeal joint (as part of monoarticular or oligoarticular episode)	2
Characteristics of symptomatic episode(s) (ever)	Erythema overlying affected joint (patient reported or physician observed) Inability to bear touch or pressure to affected joint Great difficulty with walking or inability to use affected joint	1 characteristic	1
		2 characteristics	2
		3 characteristics	3
Time course of symptomatic episode(s) (ever)	Symptomatic episode is defined as an event with the presence of ≥2 of the following criteria, irrespective of anti-inflammatory treatment: Time to maximal pain <24 hrs Resolution of symptoms in ≤14 days Complete resolution (to baseline level) between symptomatic episodes	1 typical episode	1
Time course of symptomatic episode(s) (ever)		Recurrent typical episodes	2
Tophus	Clinical evidence of tophus	Present	4
Laboratory	Serum urate	<4 mg/dL (<0.24 mmol/L)	-4
		4-<6 mg/dL (0.24-<0.36 mmol/L)	0
		6-<8 mg/dL (0.36-<0.48 mmol/L)	2
		8-<10 mg/dL (0.48-<0.60 mmol/L)	3
		≥10 mg/dL (≥0.60 mmol/L)	2
	Synovial fluid analysis of a symptomatic (ever) joint or bursa for MSU crystals	MSU crystal negative	-2
Imaging^c	Imaging evidence of urate deposition in symptomatic (ever) joint or bursa	Present	4
Imaging^c	Imaging evidence of gout-related joint damage	Present	4
^aA web-based calculator can be accessed at https://goutclassificationcalculator.auckland.ac.nz, and through the ACR and EULAR websites. ^bSymptomatic episodes are periods that include any swelling, pain, and/or tenderness in a peripheral joint or bursa. ^cIf imaging is not available, score these items as 0. Source: Neogi, 2015

Laboratory Testing

Diagnosis

Polarized Light Microscopy

The detection of MSU crystals in synovial fluid using polarizing microscopy is diagnostic of gout and the preferred approach for diagnosis. MSU crystals are needle shaped and negatively birefringent. Absence of these crystals does not necessarily eliminate the possibility of gout, but it makes gout less likely (as reflected by a negative value in the ACR/EULAR classification criteria scoring system). Although this method is preferred for diagnosis, it is not always feasible. Joint aspiration may be difficult in small joints, and polarized light microscopy is not available in all clinical settings. As such, MSU crystal detection is an unfeasible universal diagnostic standard, but this method of evaluation should be used when possible.

Serum Uric Acid

The serum urate concentration is considered a mandatory element of the classification criteria scoring system; in other words, the score cannot be calculated without it. In patients with gout, serum urate concentrations are generally elevated; however, serum urate levels are not always elevated at the time of an acute gout flare. Ideally, serum urate is measured >4 weeks after an acute attack. Treatment with urate-lowering therapy interferes with serum urate measurement.

Synovial Fluid Examination

Additional synovial fluid examination is sometimes required after MSU crystal analysis and is generally useful to differentiate between gout and septic arthritis. Helpful tests include absolute white blood cell (WBC) count, gram stain, and culture.

Monitoring

For patients receiving urate-lowering medication, serum urate concentrations should be monitored and maintained at <6 mg/dL (360 mmol/L), given that urate is generally soluble up to that level. A lower serum urate level (<5 mg/dL; 300 mmol/L) may facilitate faster dissolution of crystals in patients with severe gout (tophi, chronic arthropathy, frequent attacks) until crystal dissolution is total and gout has resolved. Serum urate concentrations of <3 mg/dL are not recommended for the long term because some studies suggest that uric acid might protect against various neurodegenerative diseases.

Additional Testing

HLA-B*5801 Genotyping

HLA-B*5801 genotyping may be indicated in certain patient populations before initiation of allopurinol therapy to identify patients who are at increased risk for developing severe cutaneous adverse reactions to allopurinol (allopurinol hypersensitivity reaction).