How do I differentiate gout from pseudogout in an older adult with acute monoarthritis and what are the recommended acute and long‑term treatment strategies?

Differentiating Gout from Pseudogout in Older Adults with Acute Monoarthritis

Joint aspiration with synovial fluid analysis under compensated polarized light microscopy is mandatory to definitively distinguish gout from pseudogout, as clinical features alone cannot reliably differentiate these conditions. 1, 2, 3

Definitive Diagnostic Approach

When Joint Aspiration is Required

• Arthrocentesis must be performed whenever septic arthritis cannot be clinically excluded, when this is the first suspected crystal arthropathy attack, or when the diagnosis remains uncertain after clinical assessment. 1
• Gram stain and culture must be performed on all synovial fluid samples even when crystals are identified, because crystal arthritis and septic arthritis can coexist. 1

Crystal Identification Under Polarized Microscopy

• Monosodium urate (MSU) crystals in gout appear as needle-shaped, negatively birefringent crystals with 84% sensitivity and 100% specificity. 1
• Calcium pyrophosphate dihydrate (CPPD) crystals in pseudogout appear as rhomboid-shaped, weakly positively birefringent crystals. 2, 4
• Compensated polarized light microscopy is the gold standard technique for differentiating these crystal types. 2, 3, 4

Clinical Features That Suggest Gout vs Pseudogout

Features More Suggestive of Gout

• First metatarsophalangeal joint involvement (podagra) has 96% sensitivity and 97% specificity for gout, with a likelihood ratio of 30.64. 1
• Rapid onset with maximum pain intensity within 6-12 hours strongly favors gout. 1
• Male gender, though gout in older adults increasingly affects women, particularly those on diuretics. 5
• History of hyperuricemia, though approximately 10% of acute gout patients have normal serum uric acid during an attack. 1
• Associated risk factors: chronic kidney disease (RR 4.95), obesity (RR 3.81), hypertension (RR 3.93), diuretic use (RR 1.72). 1

Features More Suggestive of Pseudogout

• Larger joint involvement (knees, wrists, shoulders) is more typical of pseudogout than gout. 5, 4
• Pseudogout often follows trauma, surgery, or acute medical illness such as ischemic heart disease. 4
• Chronic polyarticular presentation resembling osteoarthritis or rheumatoid arthritis is more common with pseudogout. 5
• Radiographic evidence of chondrocalcinosis supports pseudogout diagnosis. 2

Overlapping Features (Cannot Reliably Differentiate)

• Both conditions can present as acute monoarthritis with severe pain, swelling, and erythema. 2, 5
• Both can be polyarticular, especially in older adults. 2, 5
• Both can mimic septic arthritis clinically. 2
• In 20% of cases, gout affects the knees, making joint distribution alone unreliable for differentiation. 2

Imaging Strategies When Aspiration is Not Feasible

First-Line Imaging: Ultrasound

• Ultrasound should be the initial imaging modality when joint aspiration cannot be performed, with the "double contour sign" having 74% sensitivity and 88% specificity for gout. 1
• Always include bilateral first metatarsophalangeal joints in ultrasound examination, even if asymptomatic. 1
• Ultrasound can detect tophi with 65% sensitivity and 80% specificity. 1

Second-Line Imaging: Dual-Energy CT

• DECT should be considered when ultrasound is negative but clinical suspicion remains high, particularly in patients with disease duration >2 years, with 85-100% sensitivity and 83-92% specificity for MSU crystal deposition. 1
• DECT is less sensitive in early disease (<2 years duration). 1

Limited Role of Plain Radiography

• Plain radiographs are useful only for assessing chronic structural damage or excluding alternative diagnoses and should not be used as the primary diagnostic modality. 1, 2
• Radiographic chondrocalcinosis supports pseudogout but does not confirm acute CPPD arthritis. 2

Acute Treatment Strategies

First-Line Anti-Inflammatory Therapy (Same for Both Conditions)

• Initiate treatment immediately with corticosteroids, NSAIDs, or colchicine—choice depends on comorbidities rather than crystal type. 6, 7
• In older adults with multiple comorbidities, oral corticosteroids (prednisone 0.5 mg/kg/day for 5-10 days) are often preferred over NSAIDs due to renal and cardiovascular risks. 7, 8
• Low-dose colchicine (1.2 mg loading dose, then 0.6 mg one hour later) is equally effective as high-dose with fewer adverse effects. 6, 8
• NSAIDs should be avoided in patients with significant renal impairment, cardiovascular disease, or gastrointestinal risk. 7, 8

Colchicine Dose Adjustment in Renal Impairment

• Reduce colchicine to 0.5 mg daily or every other day if creatinine clearance is 30-50 mL/min. 8
• Colchicine should be avoided until renal function is assessed in older adults. 7

Long-Term Management Strategies

Gout-Specific Long-Term Management

• Urate-lowering therapy (ULT) is the cornerstone of gout management and should be initiated in patients with ≥2 gout flares per year, presence of tophi, or radiographic gouty arthropathy. 6, 8
• Start allopurinol at 100 mg daily, increasing by 100 mg every 2-4 weeks until serum uric acid <6 mg/dL (or <5 mg/dL for severe gout with tophi). 6, 8
• Prophylactic anti-inflammatory therapy (colchicine 0.5-1 mg daily) is mandatory for at least 6 months when initiating ULT to prevent mobilization flares. 8
• Never stop ULT during an acute attack, as this perpetuates the cycle of recurrent flares. 8

Pseudogout Long-Term Management

• No disease-modifying therapy exists for pseudogout comparable to ULT for gout. 5
• Management focuses on treating acute flares and addressing underlying metabolic conditions (hyperparathyroidism, hemochromatosis, hypomagnesemia). 3, 5

Lifestyle Modifications for Gout

• Weight loss if obese, avoid alcohol (especially beer and spirits), eliminate sugar-sweetened drinks and high-fructose foods, reduce red meat and seafood intake, encourage low-fat dairy products. 8
• Regular exercise reduces mortality associated with hyperuricemia. 8

Medication Adjustments for Gout

• Thiazide and loop diuretics should be substituted if possible, switching to losartan (which has modest uricosuric effects) or calcium channel blockers for hypertension. 8
• Diuretics are the most common iatrogenic cause of gout in older adults with hypertension. 8

Critical Pitfalls to Avoid

• Never diagnose gout or pseudogout based on hyperuricemia or clinical features alone without crystal confirmation—up to 80% of patients with hyperuricemia never develop gout. 1
• Never assume a single crystal type—aspirate multiple joints if polyarticular, as simultaneous gout and pseudogout can affect different joints in the same patient. 9
• Never exclude septic arthritis based on crystal identification alone—perform Gram stain and culture on all synovial fluid samples. 1, 2
• Never stop aspirin for cardiovascular indications despite mild uric acid-elevating effects. 8
• Inadequate patient education about dietary triggers and self-management reduces treatment success. 8