What is the appropriate approach to diagnosing gout?

Diagnosis of Gout

Synovial fluid analysis demonstrating needle-shaped, negatively birefringent monosodium urate (MSU) crystals under polarized light microscopy is the definitive diagnostic test for gout, but when aspiration is not feasible, validated clinical algorithms combined with ultrasound imaging achieve diagnostic accuracy exceeding 80%. 1

When Joint Aspiration Is Mandatory

Arthrocentesis with synovial fluid analysis must be performed in the following situations:

• Septic arthritis cannot be clinically excluded—gout and bacterial infection coexist in up to 4% of cases, with reported mortality and limb loss when infection is missed 1, 2
• First suspected gout attack in a patient with no prior crystal-proven diagnosis 1, 3
• Atypical presentations including polyarticular involvement, unusual joint distribution, or systemic symptoms such as fever 1, 2
• Gram stain and culture must be performed on all aspirated fluid even when MSU crystals are identified, because coexistence of gout and septic arthritis carries substantial morbidity 1, 2

Joint aspiration should only be performed when an experienced clinician can minimize infection risk, a polarizing microscope with trained operator is available, and the joint can be accessed without substantial patient discomfort 1

Clinical Diagnosis Without Aspiration

Clinical diagnosis is appropriate when the presentation is unambiguous and infection is unlikely. 1

High-Value Clinical Features Supporting Gout:

• Podagra (first metatarsophalangeal joint involvement)—sensitivity 96%, specificity 97%, likelihood ratio 30.64 2, 4
• Rapid pain onset reaching maximum intensity within 6–24 hours 1, 2, 4
• Erythema over the affected joint 1, 3
• History of prior similar acute arthritis episodes 1, 3, 5
• Male gender 1, 3
• Cardiovascular comorbidities (hypertension, ischemic heart disease) 1, 3

ACR/EULAR Clinical Algorithm:

The 2015 ACR/EULAR classification criteria achieve 92% sensitivity and 89% specificity with imaging (or 85% sensitivity and 78% specificity without imaging) when a score ≥8 points is reached 1, 6. Several validated algorithms demonstrate sensitivities and specificities >80% for diagnosing gout 1

Example of straightforward clinical diagnosis: A middle-aged man with podagra, rapid pain onset, no fever or systemic signs, hyperuricemia, and multiple risk factors (obesity, hypertension, diuretic use) can be diagnosed clinically without aspiration 1

Imaging Modalities

First-Line: Ultrasound

• Ultrasound should be the initial imaging study when clinical diagnosis is uncertain and aspiration is not feasible 2, 3, 6
• Always scan bilateral first metatarsophalangeal joints, even if asymptomatic, as this is the disease-specific target site 2, 3
• "Double contour sign" on cartilage surfaces: sensitivity 74%, specificity 88% 1, 2, 6
• Tophi detection: sensitivity 65%, specificity 80%, appearing as hyperechoic masses with "wet clumps of sugar" appearance 2, 7
• Ultrasound performs better in late disease (>2 years duration, 63% sensitivity) versus early disease (<2 years, 50% sensitivity) 2
• Ultrasound can guide aspiration of joint fluid or tophus material when direct joint access is difficult 7

Second-Line: Dual-Energy CT (DECT)

• DECT should be considered when ultrasound is negative but clinical suspicion remains high, particularly in patients with disease duration >2 years 2, 3, 6
• Sensitivity 85–100%, specificity 83–92% for detecting MSU crystal deposition 1, 2, 8
• DECT provides color-coded images showing MSU deposits, distinguishing them from other soft tissue pathology 2, 8
• Less sensitive in early disease (<2 years) or patients with shorter flare history 2, 6
• More expensive and involves radiation exposure compared to ultrasound 2

Limited Role: Plain Radiography

• Plain radiographs are useful only for assessing chronic structural damage or excluding alternative diagnoses—they should not be the primary diagnostic modality for acute gout 1, 2, 6
• Radiographs are frequently normal in early or acute gout, showing at most nonspecific soft-tissue swelling 2, 9

Laboratory Testing

Serum Uric Acid

• Hyperuricemia alone cannot diagnose gout—specificity is only 53–61% 2, 3
• Approximately 10% of patients with acute gout have normal serum uric acid levels during an attack because uric acid behaves as a negative acute phase reactant during inflammation 2, 3
• Only 22% of asymptomatic individuals with serum uric acid >9 mg/dL develop gout within 5 years 2, 3
• Conversely, absence of hyperuricemia has a markedly low likelihood ratio for gout, essentially ruling it out in the context of recurrent monoarticular knee pain 2, 3
• Serum uric acid should be measured for long-term management decisions but has limited diagnostic value during acute attacks 2

24-Hour Urinary Uric Acid

• Measure in selected patients with family history of young-onset gout, onset under age 25, or history of renal calculi to identify urate overproducers versus underexcretors 2

Risk Factor and Comorbidity Assessment

Systematically evaluate the following risk factors and comorbidities:

Risk Factor/Comorbidity	Relative Risk
Chronic kidney disease	4.95 [2]
Hypertension	3.93 [2]
Obesity	3.81 [2]
Diuretic use	1.72 [2]

• Medications: thiazide diuretics, loop diuretics, low-dose aspirin, cyclosporine, tacrolimus 1, 2, 3
• Alcohol consumption, particularly beer and spirits 2, 5
• Diet high in meat, shellfish, and high-fructose corn syrup 1, 2, 5
• Associated comorbidities: renal impairment, ischemic heart disease, heart failure, diabetes mellitus, dyslipidemia 1, 2, 3, 4

Practical Diagnostic Algorithm

Step 1: If septic arthritis cannot be excluded, fever is present, or this is the first suspected gout attack → perform joint aspiration with crystal analysis, Gram stain, and culture 1, 2, 3

Step 2: If classic podagra with typical features (rapid onset, erythema, male sex, prior attacks, no fever, multiple risk factors) and infection is unlikely → diagnose gout clinically using validated criteria 1, 3

Step 3: If clinical diagnosis is uncertain and aspiration is not feasible → obtain ultrasound of symptomatic joint(s) plus bilateral first MTP joints 2, 3, 6

Step 4: If ultrasound is negative but suspicion remains high, especially in disease >2 years → consider DECT to detect MSU crystal deposition 2, 3, 6

Step 5: If all testing is inconclusive → refer to rheumatology for expert evaluation 6

Critical Pitfalls to Avoid

• Never diagnose gout based on hyperuricemia alone—up to 80% of patients with hyperuricemia never develop gout 2, 3
• Never exclude septic arthritis based solely on clinical appearance—if infection cannot be ruled out, aspiration with Gram stain and culture is mandatory regardless of crystal identification 1, 2
• Do not rely on imaging alone—patient history, physical examination, and laboratory findings must be integrated 2
• Ultrasound sensitivity is significantly lower in early disease (<2 years: 50% vs. >2 years: 63%), so negative ultrasound does not exclude gout in recent-onset cases 2
• All imaging must be performed and interpreted by trained operators to ensure accuracy 2