Criteria for Diagnosis of Acute Gouty Arthritis¹

• Presence of characteristic urate crystals in joint fluid
• A tophus proven by chemical means or polarized light microscopy to contain urate crystals
• Six of the following 12 clinical, laboratory & radiographic findings:
  • More than 1 attack of acute arthritis
  • Maximum inflammation developing within 1 day
  • Monoarticular arthritis attack
  • Redness observed over affected joints
  • First metatarsophalangeal joint pain or swelling
  • Unilateral first metatarsophalangeal joint attack
  • Unilateral tarsal joint attack
  • Tophus (proven or suspected)
  • Hyperuricemia
  • Asymptomatic swelling within a joint on x-ray
  • Subcortical cysts without erosions on x-ray
  • Joint fluid culture negative for organisms during attacks

The combination of crystals, tophi &/or 6 or more criteria is highly suggestive of gout

Classification of Hyperuricemia

• Primary hyperuricemia
  • Uric acid saturation arises without coexisting diseases or drugs that alter uric acid production or excretion

• Secondary hyperuricemia
  •  Excessive uric acid production or diminished renal clearance occurs as a result of a disease, drug, dietary product or toxin

Causes of Secondary Hyperuricemia

• Excessive uric acid production:
  • Inherited enzyme defects (eg hypoxanthine-guanine phosphoribosyltransferase deficiency)
  • Clinical disorders (eg myeloproliferative & lymphoproliferative disorders, malignancies, psoriasis, Down syndrome)
  • Induced by diet, drugs, or toxins (eg ethanol, excessive purine in diet, fructose, vitamin B12 deficiency, Nicotinic acid, cytotoxic drugs, Warfarin)

• Decreased renal clearance:
  • Chronic renal insufficiency, volume depletion (eg heart failure, volume loss), obesity, diabetic or starvation ketoacidosis, lactic acidosis, hyperparathyroidism, hypothyroidism, sarcoidosis
  • Induced by diet or drugs (eg Aspirin, diuretics, Cyclosporine, Tacrolimus, Ethambutol, Pyrazinamide, ethanol, Levodopa)

Clinical Phases of Gout 

Acute Gout

• Usually manifests as an acute, self-limiting, monoarticular inflammatory arthritis in majority of patients
• Lower extremity joints are affected more often than upper extremity joints
  • Joints most commonly affected include the 1st metatarsophalangeal joint (podagra), forefoot, ankle, knee, wrist, elbow & finger joints

• Extra-articular sites (eg olecranon bursa & Achilles tendon) may also be involved
• Attacks may occur & last from a few days to 2-3 week, with resolution of all inflammatory signs
  • Early attack: <12 hours after onset of attack
  • Well-established attack: 12-36 hours after onset of attack
  • Late attack: >36 hours after attack onset

• Severity of acute gouty arthritis attack (based on patients’ pain assessment):
  • Mild: ≤4
  • Moderate: 5-6
  • Severe: ≥7

Intercritical Gout

• Periods in between attacks when patient is free of symptoms

Chronic Gout

• After intermittent attacks (>3 acute attacks/year) & remissions, the chronic phase follows
• Polyarticular flares of gouty arthritis occur, & associated with bony erosions & deformities
• Chronic tophaceous gout:
  • Marked by polyarticular arthritis & the formation of tophi which are chalky deposits of monosodium urate
  • Tophi are usually painless, appearing as firm, nodular or fusiform masses, located subcutaneously
  • Risk factors include polyarticular presentation, serum urate level >0.54 mmol/L (9 mg/dL), age of ≥40 years old at disease onset

• Disease severity
  • Mild - simple chronic tophaceous gouty arthropathy, 1 joint affected, stable
  • Moderate - simple chronic tophaceous gouty arthropathy, 2-4 joints affected, stable
  • Severe - chronic tophaceous gouty arthropathy of >4 joints OR ≥1 unstable, complicated, severe articular tophus/tophi

• Presence of urate nephropathy or urate renal calculi

Gout Classification Criteria¹

• Developed by the American College of Rheumatology (ACR) & the European League Against Rheumatism (EULAR) in 2015
• The new criteria is based on the presence of MSU crystals, imaging modalities, & clinical parameters
• Provides a scoring system for a patient’s symptomatic episode, regardless of the clinical phase
• A total score of >8 confirms the diagnosis of gout
• Entry criterion is defined as at least 1 episode of swelling, pain, or tenderness in a peripheral joint or bursa
• Sufficient criterion should be considered with the presence of urate crystals in a symptomatic joint or bursa, or a positively-identified tophus
• The classification criteria should be used if sufficient criterion is not met

Risk factors for gout & associated comorbidity should be assessed

Risk factors associated with gout:

• Hyperuricemia
  • Single most important risk factor for developing gout

• Male sex
• Purine-rich diet (eg meat, seafood)
• Alcohol intake
• Diuretics

Metabolic abnormalities associated with gout:

• Hypertension
• Obesity
• Dyslipidemia
• Hyperglycemia & insulin resistance

Comorbidities associated with gout:

• Coronary artery disease
• Type 2 diabetes mellitus
• Renal insufficiency
• Metabolic syndrome
• Kidney stone

Additional laboratory exams to detect the presence of associated comorbidities in patients with gout:

• Upon detection of associated risk factors & comorbidities, these should be addressed as an important part of the management of gout
  • Complete blood count to exclude infection, lymphoproliferative or myeloproliferative disorders
  • Serum creatinine/urea to exclude renal disease leading to hyperuricemia or to detect renal disease secondary to urate nephropathy or nephrolithiasis
  • Blood glucose to detect the presence of diabetes/insulin resistance
  • Lipid profile to detect hypertriglyceridemia & low HDL cholesterol
  • Urinalysis showing presence of blood &/or protein may suggest renal disorders
  • Rapid polymerase chain reaction-based HLA-B*5801 screening detects patients at high risk for severe Allopurinol hypersensitivity reaction (eg Koreans with > stage 3 CKD, Han Chinese, Thai)

Specific investigations for confirmation of gouty arthritis

Synovial fluid analysis

• Demonstration of MSU crystals in synovial fluid or tophus aspirates gives a definitive diagnosis of gout
  • MSU crystals are needle-shaped & they exhibit strong birefringence under polarized light

• It is recommended to search for MSU crystals in all synovial fluid samples obtained from undiagnosed inflamed joints
• Identification of MSU crystals from asymptomatic joints may allow definite diagnosis in intercritical periods wherein patients are free of symptoms

Serum urate levels

• Hyperuricemia defined as serum urate level >6.8-7 mg/dl
• Although hyperuricemia is the most important risk factor for gout, this does not confirm or exclude gout
  • Many patients with hyperuricemia do not develop gout
  • During acute attacks, serum urate levels may be normal in about 10% of cases

• It will be best to measure serum urate levels 2-3 week after an attack
• Upper limit of serum urate level:
  • Male & postmenopausal women: 0.42 mmol/L or 7 mg/dL
  • Premenopausal women: 0.36 mmol/L or 6 mg/dL

Plain Radiography/Skeletal X-ray

• Usually normal in acute gouty arthritis, although there may be reversible soft tissue swelling around the involved joint
• In chronic tophaceous gout, typical radiographic findings include erosions with sclerotic margins & overhanging edges of bones, or calcification in some tophi
  • Presence of a thin, overhanging calcified edge is highly suggestive of gout
  • Joint space is usually preserved until late stages of the disease

Ultrasonography (US)

• Can detect crystals deposited on cartilaginous surfaces as well as tophaceous material & typical erosions

Computed Tomography (CT)

• Allows excellent visualization of tophi
• May assist in differentiating tophi from other subcutaneous nodules

Magnetic Resonance Imaging (MRI)

• Findings are not specific for the diagnosis of gout but allow early detection of tophi & bone erosion
• Method of determining the extent of disease in tophaceous gout & may provide information regarding the patterns of deposition & spread of MSU crystals