What is the management approach for elevated C-Reactive Protein (CRP) and hyperuricemia?

Management Approach for Elevated CRP and Hyperuricemia

The management of elevated C-reactive protein (CRP) and hyperuricemia should focus on identifying underlying causes, implementing appropriate lifestyle modifications, and initiating pharmacologic therapy targeting urate-lowering when indicated, with the goal of reducing inflammation and preventing complications such as gout and cardiovascular disease.

Diagnostic Evaluation

• Consider potential causes of hyperuricemia and elevated CRP for all patients, including assessment of comorbidities such as hypertension, heart failure, hyperlipidemia, and organ transplant status 1
• Evaluate for medications that may elevate serum urate levels, including thiazide and loop diuretics, niacin, and calcineurin inhibitors 1
• For patients with hyperuricemia and elevated CRP, perform a thorough clinical evaluation including history and physical examination for symptoms of arthritis and signs such as tophi and synovitis 1
• Consider screening for uric acid overproduction (via urine uric acid evaluation) in patients with early-onset hyperuricemia (before age 25) or history of urolithiasis 1

Non-Pharmacologic Management

• Implement diet and lifestyle modifications as foundational treatment for all patients with hyperuricemia and elevated CRP 1:

  • Limit consumption of purine-rich meat and seafood 1
  • Reduce consumption of high fructose corn syrup-sweetened beverages 1
  • Encourage consumption of low-fat or non-fat dairy products 1
  • Reduce alcohol consumption, particularly beer 1
  • Complete abstinence from alcohol during periods of active arthritis 1

• Recognize that diet and lifestyle measures alone typically provide insufficient serum urate-lowering effects (only ~10-18% decrease in serum urate) for many patients 1

Pharmacologic Management

For Hyperuricemia:

• Initiate urate-lowering therapy (ULT) when clinically indicated, with the goal of achieving serum urate below 6 mg/dL at minimum 1

• For patients with greater disease severity (tophi or chronic tophaceous gouty arthropathy), target serum urate below 5 mg/dL 1

• First-line ULT options:

  • Allopurinol: Start at 100 mg daily (50 mg daily in patients with stage 4 or worse CKD) and titrate upward to achieve target serum urate 1, 2
  • Febuxostat: An alternative first-line XOI therapy 1
  • Probenecid: Consider as alternative first-line therapy if XOI drugs are contraindicated, but not recommended as first-line in patients with creatinine clearance <50 mL/min 1

• For refractory cases:

  • Consider combination therapy with XOI plus uricosuric agents (probenecid, fenofibrate, or losartan) 1
  • Pegloticase may be considered as a third-line agent in cases of refractory disease with failure of appropriately dosed oral ULT 1

For Elevated CRP:

• Address the underlying cause of inflammation 1
• For CRP levels ≥2 mg/L with concomitant hyperuricemia, consider more aggressive urate-lowering therapy due to increased cardiovascular risk 3
• For highly elevated CRP (>10 mg/L), evaluate for non-cardiovascular causes of inflammation 1

Special Considerations

• Patients with both elevated CRP (≥2 mg/L) and hyperuricemia have increased risk of major adverse cardiovascular events, suggesting potential benefit from combined ULT and anti-inflammatory therapy 3
• Hyperuricemia appears to be independently associated with hypertension, even when CRP is not elevated, suggesting the importance of urate control regardless of inflammatory status 4
• In patients with gout, both serum ferritin and high-sensitivity CRP levels are significantly elevated and may be involved in the pathogenesis 5
• Monitor both CRP and uric acid levels in patients with conditions associated with both markers, such as psoriasis 6

Referral Considerations

• Consider referral to a specialist in cases with 1:
  • Unclear etiology of hyperuricemia
  • Refractory signs or symptoms of gout
  • Difficulty achieving target serum urate level, particularly with renal impairment
  • Multiple or serious adverse events from pharmacologic ULT

Monitoring

• Regularly assess serum urate levels to ensure target levels are achieved 1
• Monitor for resolution of inflammatory markers (CRP) with treatment 7
• Evaluate for clinical improvement in symptoms and signs of inflammation 1