Diagnosis
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
ACR/EULAR gout classification criteria and scoring
ACR/EULAR Gout Classification Criteriaa
Criteria
Categories
Score
Clinical
Clinical
Ankle or midfoot
1
Pattern of joint/bursa involvement during symptomatic episode(s) everb
Involvement of the first metatarsophalangeal joint
2
Characteristics of symptomatic episode(s) ever
Erythema overlying affected joint (patient reported or physician observed)
Can't bear touch or pressure to affected joint
Great difficulty with walking or inability to use affected joint
One characteristic
1
Two characteristics
2
Three characteristics
3
Time course of episode(s) ever
Presence (ever) of ≥2, irrespective of anti-inflammatory treatment
Time to maximal pain <24 hours
Resolution of symptoms in ≤14 days
Complete resolution (to baseline level) between symptomatic episodes
One typical episode
1
Recurrent typical episodes
2
Tophus
Clinical evidence of tophus
Present
4
Laboratory
Serum urate
<4 mg/dL (<0.24 mmol/L)c
-4
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
Monosodium urate (MSU) negative
-2
Imagingd
Imaging evidence of urate deposition in symptomatic (ever) joint or bursa
Present
4
Imaging evidence of gout-related joint damage
Present
4
a A web-based calculator can be accessed at: https://goutclassificationcalculator.auckland.ac.nz , and through the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) web sites.
b Symptomatic episodes are periods of symptoms that include any swelling, pain, and/or tenderness in a peripheral joint or bursa.
c If serum urate level is <4 mg/dL (<0.24 mmol/L), subtract 4 points; if serum urate level is ≥4−<6 mg/dL (≥0.24−<0.36 mmoles/L), score this item as 0.
d If imaging is not available, score these items as 0.
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 genotyping – recommended prior to initiation of allopurinol therapy (Saito, Clinical Pharmacogenetics Implementation Consortium, 2016)
To identify patients at increased risk for developing severe cutaneous adverse reactions to allopurinol (allopurinol hypersensitivity reaction)
Highest HLA-B*58:01 allele frequencies are found in Asian populations – up to 20% in Taiwan, Singapore, and among Han Chinese
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
Monitoring
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)
Background
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