What is the role of C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) in the diagnosis and management of orthopaedic infections?

CRP and ESR in Orthopaedic Infections

CRP and ESR are essential first-line screening tests for orthopaedic infections, but they have significant limitations with false-negative rates of 12-27%, particularly for low-virulence organisms, and should never be used alone to exclude infection. 1

Diagnostic Performance

CRP Characteristics

• Sensitivity: 73-91% and specificity: 81-86% using a cutoff of 13.5 mg/L for prosthetic joint infection 1
• Rises within 12-24 hours and peaks at 48 hours, making it superior for acute infections 2
• Returns to baseline within 2 months post-surgery under normal circumstances 1
• Critical limitation: Normal CRP occurs in 32% of culture-positive periprosthetic joint infections, especially with coagulase-negative Staphylococcus and Propionibacterium acnes 3

ESR Characteristics

• Sensitivity: 85% for chronic periprosthetic joint infection 4
• Optimal cutoff of 27 mm/h for prosthetic joint infection 1
• Longer half-life than CRP due to fibrinogen, making it better for monitoring chronic inflammatory conditions 5
• Can remain elevated for 1-2 years post-operatively even without infection 1

Combined Testing Algorithm

The AAOS strongly recommends using ESR, CRP, and interleukin-6 together for suspected periprosthetic joint infection 1, 2

When using the combination approach:

• Abnormal results in at least 2 of 3 tests (CRP >0.93 mg/L, ESR >27 mm/h, fibrinogen >432 mg/dL) yields 93% sensitivity, 100% specificity, and 97% accuracy 1
• Interleukin-6 combined with CRP shows excellent sensitivity and higher predictive value than traditional markers alone 1, 2

Organism-Specific Patterns

High-Virulence Organisms

• Staphylococcus aureus: Mean CRP 112.2 mg/L, mean ESR 81.0 mm/h 4
• Streptococcus species: Mean CRP 114.6 mg/L, mean ESR 66.1 mm/h 4
• Gram-negative organisms: Mean CRP 87.4 mg/L 4

Low-Virulence Organisms

• Coagulase-negative Staphylococcus: Mean CRP 66.0 mg/L, mean ESR 68.3 mm/h 4
• Culture-negative cases: Mean CRP 41.0 mg/L, mean ESR 57.4 mm/h 4
• 70% of infections with normal CRP are caused by low-virulence organisms 3

Clinical Application Algorithm

Step 1: Initial Screening

• Obtain baseline CRP and ESR for any suspected orthopaedic infection 2
• Do not rely on normal values to exclude infection—proceed to joint aspiration if clinical suspicion remains high 2, 3

Step 2: Interpretation Based on Clinical Context

• Pain at rest or night pain: Characteristic of infection, even with normal inflammatory markers 6
• Pain on weight-bearing only: Suggests mechanical loosening rather than infection 6
• Absence of fever, erythema, or warmth: Does not exclude chronic infection 6

Step 3: Mandatory Joint Aspiration

• Proceed with synovial fluid analysis when CRP/ESR are elevated OR when clinical suspicion is high despite normal markers 6
• Withhold antibiotics for at least 2 weeks prior to aspiration when clinically feasible 2, 6
• Synovial fluid alpha-defensin achieves 97% sensitivity and 96% specificity, increasing to 100% specificity when combined with synovial CRP 1

Step 4: Monitoring During Treatment

• Recheck CRP and ESR at 2-4 week intervals during active treatment 2
• CRP normalizes faster than ESR (21 days vs 28 days post-treatment), making it more useful for monitoring treatment response 7
• Delta change (percentage improvement) in ESR and CRP has no diagnostic value for determining timing of two-stage reimplantation 8

Critical Pitfalls to Avoid

Never Exclude Infection Based on Normal Markers Alone

• 23% of culture-positive infections have both normal ESR and normal physical examination findings 3
• Up to 32% of culture-positive infections have normal CRP levels 3
• Peripheral WBC counts are often normal in prosthetic joint infections and should not be used for screening 6

Recognize Confounding Factors

• Underlying inflammatory arthropathy makes serologic tests difficult to interpret 1
• Recent surgery: CRP can remain elevated for up to 2 months, ESR for 1-2 years 1
• Low-virulence organisms: Systematically produce lower inflammatory marker elevations 3, 4

Avoid Premature Aspiration

• Do not aspirate patients currently on antibiotics unless clinically urgent—wait at least 2 weeks off antibiotics to maximize culture yield 2, 6

Monitoring Chronic Inflammatory Conditions

For non-infectious inflammatory arthritis:

• Measure ESR at baseline, then 1-3 month intervals during active disease 2
• Once remission achieved, monitor every 3-6 months 2
• ESR incorporated into DAS28-ESR composite scores for rheumatoid arthritis disease activity 2