What is the diagnosis and treatment for a patient presenting with acute gout?

Gout: Complete History, Physical Examination, Diagnosis, and Treatment

History and Physical Examination

Key Historical Features to Elicit

Classic presentation includes:

• Podagra (first metatarsophalangeal joint involvement) with rapid onset of severe pain, swelling, and erythema is the hallmark presentation 1
• Rapid response to colchicine in previous episodes supports the diagnosis 1
• History of tophi (subcutaneous urate crystal deposits) 1
• Timing: symptoms typically reach maximum intensity within 12-24 hours 1
• Pattern: monoarticular involvement initially, though polyarticular attacks can occur 1

Risk factors and comorbidities to assess:

• Renal function impairment (fourfold increase in mortality from kidney disease in gout patients) 1
• Cardiovascular risk factors and metabolic syndrome (hyperuricemia and gout are red flags for these conditions) 1
• Diabetes and hypertension screening 1
• Medication history: thiazide diuretics, loop diuretics, low-dose aspirin, and niacin elevate serum urate 2
• Dietary factors: alcohol consumption (especially beer and spirits), high-fructose corn syrup beverages, purine-rich foods 1, 3
• Family history of young-onset gout (onset before age 25) or renal calculi 2

Physical Examination Findings

Joint examination should document:

• Severity of inflammation: erythema, warmth, swelling, and tenderness 1
• Number and location of affected joints (monoarticular vs. polyarticular) 1
• Presence of tophi on ears, fingers, elbows, or other locations 1
• Range of motion limitation due to pain 1

Diagnostic Approach

Gold Standard Diagnosis

Synovial fluid analysis is the definitive diagnostic test 1, 2:

• Arthrocentesis with polarized light microscopy to identify needle-shaped, negatively birefringent monosodium urate (MSU) crystals 1, 2
• Gram stain and culture must be performed even when MSU crystals are identified, as gout and septic arthritis can coexist 2

When Crystal Identification Is Not Possible

Clinical diagnosis can be supported by 1:

• Classical features: podagra, tophi, rapid response to colchicine 1
• Characteristic imaging findings (dual-energy CT showing urate deposits, ultrasound showing double contour sign) 1
• Rapid onset of severe pain with swelling and erythema, especially in the first MTP joint 2

Laboratory Testing

Essential baseline tests:

• Serum uric acid (SUA): essential for management but insufficient alone for diagnosis, as levels may be normal during acute attacks 2
• Renal function (creatinine, BUN, eGFR): critical for medication selection and dosing 2
• Liver function tests: baseline assessment before initiating urate-lowering therapy 2
• Urinalysis: evaluate for crystalluria and renal involvement 2

Specialized testing in select patients:

• 24-hour urine uric acid collection: indicated for family history of young-onset gout, onset before age 25, or history of renal stones 2

Common pitfall: Do not rely solely on serum uric acid for diagnosis—many patients with hyperuricemia never develop gout, and SUA may be normal during acute flares 2

Treatment of Acute Gout

First-Line Pharmacologic Options

All three options are equally effective; choice depends on contraindications and patient factors 1:

Corticosteroids (preferred as first-line in most patients):

• Oral prednisolone 30-35 mg daily for 5 days is the simplest and most practical regimen 1, 4
• Alternative: prednisone 0.5 mg/kg/day for 5-10 days at full dose then stop, or taper over 7-10 days 4
• Intra-articular corticosteroid injection for 1-2 affected joints 1, 4
• Preferred in patients with severe renal impairment (eGFR <30 mL/min), cardiovascular disease, or contraindications to NSAIDs/colchicine 4
• Safer than NSAIDs with fewer adverse effects 1
• Monitor for dysphoria, mood disorders, elevated blood glucose, and fluid retention 1, 4
• Contraindicated in systemic fungal infections 1

NSAIDs at full FDA-approved doses:

• No single NSAID is superior to another; indomethacin has no advantage over naproxen or ibuprofen 1
• Contraindicated in renal disease, heart failure, cirrhosis, or significant cardiovascular risk 1
• Adverse effects: dyspepsia, GI bleeding, ulcers, perforations 1

Low-dose colchicine (most effective within 12 hours of symptom onset):

• Loading dose: 1.2 mg followed by 0.6 mg one hour later on day 1 1, 4
• Maintenance: 0.5-0.6 mg once or twice daily 4
• Low-dose regimen as effective as high-dose with significantly better safety profile 1
• Contraindicated in severe renal impairment (eGFR <30 mL/min) or with strong CYP3A4/P-glycoprotein inhibitors (cyclosporine, clarithromycin) 4
• Adverse effects: diarrhea, nausea, vomiting, abdominal pain 1

Treatment Timing

Initiate pharmacologic therapy within 24 hours of acute attack onset for optimal effectiveness 1, 4

Combination Therapy for Severe Attacks

For polyarticular gout or involvement of multiple large joints, consider initial combination therapy 1, 4:

• Oral corticosteroids plus colchicine 1, 4
• Intra-articular steroids with any other modality 1
• Colchicine plus NSAIDs 1
• Do not combine NSAIDs with systemic corticosteroids due to synergistic GI toxicity 1

NPO (Nothing by Mouth) Patients

For hospitalized patients unable to take oral medications 1:

• Intra-articular corticosteroid injection for 1-2 joints (dose depends on joint size) 1
• IV or IM methylprednisolone 0.5-2.0 mg/kg 1
• Subcutaneous synthetic ACTH 25-40 IU with repeat doses as needed 1

Management of Inadequate Response

Inadequate response defined as <20% pain improvement within 24 hours or <50% improvement ≥24 hours after initiating therapy 1:

• Consider alternative diagnoses 1
• Switch to another monotherapy or add a second agent 1
• IL-1 inhibitors (canakinumab 150 mg subcutaneously) for severe refractory cases, though risk-benefit ratio remains uncertain 1, 4

Critical Management Principle

Continue established urate-lowering therapy without interruption during acute attacks 1

Long-Term Management: Urate-Lowering Therapy (ULT)

Indications for ULT

Discuss benefits, harms, costs, and preferences before initiating ULT in patients with recurrent gout 1:

• Patients with higher serum urate levels (especially >8 mg/dL) are at greater risk for recurrent attacks 1
• ULT reduces acute gout attacks after 1 year but not within the first 6 months 1

First-Line ULT: Allopurinol

Allopurinol is the first-line urate-lowering therapy 1:

• Start with 100 mg daily and increase by 100 mg weekly until SUA <6 mg/dL is achieved, without exceeding 800 mg daily 5
• Target SUA <6 mg/dL (360 μmol/L) for most patients, or <5 mg/dL for severe gout with tophi or frequent attacks 2
• Dose adjustment required for renal impairment: 200 mg daily for creatinine clearance 10-20 mL/min; ≤100 mg daily for creatinine clearance <10 mL/min 5
• Monitor SUA every 2-4 weeks during dose titration 2
• Normal serum urate levels typically achieved in 1-3 weeks 5
• Adverse effects: rash (most common), requiring discontinuation 1

Alternative ULT Options

Febuxostat:

• Equally effective as allopurinol 300 mg daily at reducing serum urate 1
• Dosing: 40-80 mg daily 1
• Adverse effects: abdominal pain, diarrhea, musculoskeletal pain 1
• More expensive than allopurinol 1
• Requires baseline and periodic liver function monitoring 2

Uricosuric agents (probenecid, benzbromarone):

• Consider for allopurinol-allergic patients or underexcretors with normal renal function and no urolithiasis history 6
• Requires baseline renal function assessment 2

Pegloticase:

• Reserved for severe refractory gout when other agents fail 1, 7
• Highly efficacious but requires IV administration every 2 weeks 7
• Co-administration with methotrexate improves response rates: 71% at Month 6 vs. 39% with pegloticase alone 7

Prophylaxis Against Flares During ULT Initiation

Mandatory prophylaxis when starting ULT to prevent treatment-induced flares 1, 4:

First-line prophylaxis:

• Low-dose colchicine 0.5-0.6 mg daily 1, 4
• Low-dose NSAIDs 1

Second-line prophylaxis:

• Low-dose prednisone <10 mg daily if colchicine and NSAIDs contraindicated 4

Duration:

• Continue for at least 3 months after initiating ULT, or for 3-6 months after reaching target uric acid 1, 2, 4
• Moderate-quality evidence supports continuing prophylaxis for more than 8 weeks 1

Monitoring During ULT

Check SUA every 2-4 weeks during dose titration 2:

• Maintain lifelong ULT once target achieved 2
• Monitor renal function periodically, especially with allopurinol 2
• Discontinuation leads to recurrence in approximately 40% of patients 2

Lifestyle Modifications

General healthy lifestyle habits are recommended, though evidence for specific interventions in gout is limited 1:

• Reduce excess body weight and perform regular exercise 1
• Smoking cessation 1
• Limit alcohol consumption, especially beer and spirits over wine 1
• Avoid sugar-sweetened drinks and high-fructose corn syrup beverages 1, 3
• Reduce purine-rich foods (organ meats, shellfish) 3
• Encourage consumption of vegetables and low-fat or nonfat dairy products 3
• Maintain fluid intake sufficient to yield daily urinary output of at least 2 liters 5

Common Pitfalls to Avoid

• Failing to perform synovial fluid analysis in atypical presentations leads to diagnostic uncertainty 2
• Relying solely on serum uric acid for diagnosis—SUA may be normal during acute attacks 2
• Delaying treatment initiation significantly reduces effectiveness 4
• Stopping urate-lowering therapy during acute flares (should be continued without interruption) 1
• Failing to provide prophylaxis when initiating ULT, leading to treatment-induced flares 4
• Using colchicine in severe renal impairment (eGFR <30 mL/min) or with strong CYP3A4 inhibitors—can cause fatal toxicity 4
• Overlooking cardiovascular risk assessment in patients with gout 2
• Not checking for drug interactions, particularly allopurinol with azathioprine, mercaptopurine, or anticoagulants 2