What is the role of Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) in diagnosing orthopaedic infections in patients with symptoms such as pain, redness, swelling, and fever?

ESR and CRP in Orthopaedic Infections

Direct Answer

The American Academy of Orthopaedic Surgeons strongly recommends using ESR and CRP together as first-line screening tests for periprosthetic joint infection, but you must use lower cutoffs than traditionally taught (ESR >10 mm/h and CRP >5 mg/L) to achieve adequate sensitivity and avoid missing infections. 1, 2, 3

Diagnostic Performance and Optimal Cutoffs

Standard vs. Optimized Thresholds

• Traditional cutoffs (ESR >30 mm/h, CRP >10 mg/L) miss too many infections and should be abandoned for screening purposes. 4
• The optimal screening cutoffs are ESR >10 mm/h and CRP >5 mg/L, which achieve 100% sensitivity with 54.7% specificity when used together. 4
• Using at least 2 of 3 abnormal tests (CRP >0.93 mg/L, ESR >27 mm/h, and fibrinogen >432 mg/dL) provides 93% sensitivity, 100% specificity, and 97% accuracy for infection diagnosis. 1, 2

Individual Test Characteristics

• CRP demonstrates 73-91% sensitivity and 81-86% specificity for prosthetic knee infection at the 13.5 mg/L cutoff. 1, 2, 3
• ESR alone has 85% sensitivity for chronic periprosthetic joint infection, but this varies significantly by organism type. 5
• CRP is superior for acute infections, rising within 12-24 hours and peaking at 48 hours. 3, 6
• ESR is better for chronic inflammatory conditions due to fibrinogen's longer half-life. 3, 6

Temporal Patterns After Surgery

Normal Postoperative Course

• Both ESR and CRP increase rapidly after surgery, peaking around postoperative day 3. 7
• CRP returns to baseline within 2 months after uncomplicated arthroplasty. 1, 7
• ESR decreases more slowly, normalizing after 3 months postoperatively. 7
• CRP persistently elevated beyond 2 months strongly suggests infection and warrants immediate joint aspiration. 2, 3

Organism-Specific Variations

High-Virulence Organisms

• Staphylococcus aureus produces significantly higher CRP (112.2 mg/L) and ESR (81.0 mm/h) compared to low-virulence organisms. 5
• Streptococcus species generate high CRP (114.6 mg/L) and moderate ESR (66.1 mm/h). 5
• Antibiotic-resistant organisms produce elevated ESR (84.3 mm/hr) and CRP (86.0 mg/L). 5

Low-Virulence Organisms

• Coagulase-negative Staphylococcus infections show lower inflammatory markers (CRP 66.0 mg/L, ESR 68.3 mm/hr), increasing false-negative risk. 5
• Culture-negative cases have the lowest values (CRP 41.0 mg/L, ESR 57.4 mm/hr), making them particularly difficult to detect. 5
• Up to 32% of culture-positive infections have normal inflammatory markers, so never rely on normal ESR/CRP to exclude infection. 3, 5

Clinical Algorithm for Using ESR and CRP

Step 1: Initial Screening

• Obtain both ESR and CRP in all patients with suspected orthopaedic infection (pain, swelling, warmth, or fever). 1, 2
• Use screening cutoffs of ESR >10 mm/h and CRP >5 mg/L to maximize sensitivity. 4
• If both are normal, infection is unlikely but not excluded—proceed based on clinical suspicion. 3

Step 2: Interpretation Based on Timing

• For acute presentations (<2 weeks): CRP is more reliable due to rapid rise and fall. 3, 6
• For chronic presentations (>3 months): ESR may be more informative for ongoing inflammation. 3, 6
• In postoperative patients <2 months: Elevated markers are expected; compare to baseline and look for failure to decline. 1, 7

Step 3: Proceed to Definitive Testing

• If either ESR or CRP is elevated, proceed immediately to joint aspiration for synovial fluid analysis. 2
• Withhold antibiotics for at least 2 weeks prior to aspiration when clinically feasible to avoid false-negative cultures. 2, 3
• Add interleukin-6 testing, which provides higher predictive value than ESR or CRP alone. 1, 2, 3

Step 4: Synovial Fluid Analysis

• Obtain synovial fluid culture, cell count with differential, leukocyte esterase, and alpha-defensin. 1
• Alpha-defensin achieves 97% sensitivity and 96% specificity, nearly matching definitive infection criteria. 1, 3
• When alpha-defensin is combined with synovial CRP, specificity increases to 100%. 1, 3

Critical Pitfalls to Avoid

False Negatives

• Never exclude infection based solely on normal ESR/CRP—sensitivity is only 85-88%, meaning 12-15% of infections are missed. 5
• Low-virulence organisms (coagulase-negative Staphylococcus) and culture-negative infections produce minimal inflammatory response. 5
• Chronic infections may present with pain alone without fever, erythema, or warmth. 2

False Positives

• Underlying inflammatory arthropathy (rheumatoid arthritis, psoriatic arthritis) elevates ESR/CRP independent of infection. 1
• Normal postoperative elevation persists for 2-3 months after uncomplicated surgery. 1, 7
• Aseptic loosening can produce mild ESR/CRP elevation—distinguish by pain pattern (weight-bearing pain suggests mechanical loosening, rest/night pain suggests infection). 2

Interpretation Errors

• Peripheral WBC counts are not elevated in most prosthetic joint infections—a normal WBC is meaningless for excluding infection. 2, 8
• Do not interpret isolated inflammatory marker elevations without clinical context—pain characteristics and timing matter. 3
• Avoid premature joint aspiration in patients on antibiotics, as this produces false-negative cultures. 2, 3

Monitoring During Treatment

• Obtain baseline CRP and ESR before initiating treatment. 8
• Recheck at 2-4 week intervals during active treatment to assess response. 3
• If values plateau or increase after initial improvement, perform repeat joint aspiration to evaluate for persistent infection. 8
• CRP normalizes faster than ESR during successful treatment due to shorter half-life. 6