How should I diagnose and manage an acute pseudo‑gout flare in a patient over 60 years old presenting with knee pain, swelling, warmth, and limited motion?

Diagnosis and Management of Acute Pseudogout in Elderly Patients with Knee Involvement

For a patient over 60 presenting with acute knee pain, swelling, warmth, and limited motion, perform immediate arthrocentesis with synovial fluid analysis to identify positively birefringent calcium pyrophosphate dihydrate (CPPD) crystals under compensated polarized light microscopy—this is the definitive diagnostic test and simultaneously excludes septic arthritis. 1, 2

Diagnostic Approach

Immediate Joint Aspiration

• Arthrocentesis is mandatory when septic arthritis cannot be clinically excluded, as the clinical presentations of pseudogout and infection overlap significantly 3
• CPPD crystals appear as rhomboid-shaped, weakly positively birefringent crystals under compensated polarized light microscopy 1, 2
• Always perform Gram stain and culture on synovial fluid even when crystals are identified, as crystal arthropathy and septic arthritis can coexist 4

Radiographic Evaluation

• Obtain plain radiographs of the affected knee to identify chondrocalcinosis—punctate and linear radiodense areas in fibrocartilage and hyaline cartilage 1, 5
• Chondrocalcinosis prevalence is 10-15% in patients aged 65-75 years and exceeds 40% in those over 80 years 1
• The calcification pattern in pseudogout is typically linear and stippled, though it can be more diffuse in patients with renal disease 6

Screen for Metabolic Associations

• Check serum calcium, phosphate, magnesium, alkaline phosphatase, and ferritin to identify secondary causes 1
• Hyperparathyroidism, hemochromatosis, hypomagnesemia, and hypophosphatemia can promote or cause chondrocalcinosis 1
• Early-onset disease (before age 60) particularly requires screening for hemochromatosis 1
• Chronic renal failure patients have a 15.8% incidence of chondrocalcinosis in those over 60 years 6

Acute Management

First-Line Treatment Options

• Initiate NSAIDs at full anti-inflammatory doses as the primary treatment for acute pseudogout attacks 1, 5
• NSAIDs completely resolved symptoms within 1 week in documented cases of acute pseudogout 5
• Avoid NSAIDs in patients with significant renal impairment, cardiovascular disease, or gastrointestinal risk 3

Corticosteroid Therapy

• Intra-articular glucocorticoid injection is highly effective for monoarticular knee involvement and avoids systemic side effects 1, 2
• Systemic glucocorticoids (oral prednisone taper) are appropriate when intra-articular injection is not feasible or for polyarticular disease 1, 7
• Use small amounts if prolonged glucocorticoid therapy is required 1

Colchicine Use

• Colchicine can be effective for acute pseudogout attacks, though evidence is less robust than for gout 1, 2
• Low-dose colchicine (0.6 mg once or twice daily) is preferred to minimize gastrointestinal side effects 2
• Avoid colchicine in severe renal impairment and with concurrent use of strong P-glycoprotein or CYP3A4 inhibitors 8

Prophylactic Management for Recurrent Attacks

Colchicine Prophylaxis

• Low-dose colchicine is the primary prophylactic agent for patients with recurrent pseudogout attacks 1, 2
• Colchicine works by inhibiting the NALP-3 inflammasome of the innate immune system, reducing crystal-induced inflammation 2
• Magnesium supplementation can be used prophylactically in patients with documented hypomagnesemia 1

Novel Therapies for Refractory Disease

• IL-1 pathway inhibitors (anakinra, canakinumab) may be considered for severe, refractory pseudogout that fails conventional therapy 2
• Methotrexate showed effectiveness in a small uncontrolled series and can be used when other treatments fail 1

Critical Pitfalls to Avoid

• Never assume pseudogout based on radiographic chondrocalcinosis alone—up to 50% of patients with chondrocalcinosis are asymptomatic, and crystal identification is required for definitive diagnosis 1
• Do not delay joint aspiration when infection cannot be excluded, as pseudogout can mimic septic arthritis with fever, leukocytosis, and elevated inflammatory markers 7
• Recognize that unlike gout, no agents are currently available to decrease CPPD crystal load or modify disease progression—treatment is purely symptomatic 1, 2
• Be aware that pseudogout can present in atypical locations (spine, acromioclavicular joint) and may have more diffuse calcification patterns in patients with chronic renal failure 5, 7, 6
• Do not overlook the association between CPPD deposition and degenerative joint disease—crystal deposition may play a pathogenic role in osteoarthritis progression 2