What is the role of Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) in diagnosing and monitoring orthopaedic conditions, particularly infections and inflammatory diseases?

ESR and CRP in Orthopaedic Practice

Primary Clinical Role: Periprosthetic Joint Infection Detection and Monitoring

ESR and CRP serve as complementary screening tools for periprosthetic joint infection (PJI), with CRP being superior for acute diagnosis and ESR more useful for chronic monitoring, but both must be combined with synovial fluid analysis for definitive diagnosis. 1, 2

Diagnostic Performance in Periprosthetic Joint Infection

• CRP demonstrates 73-91% sensitivity and 81-86% specificity for prosthetic knee infection using a cutoff of 13.5 mg/L 1, 2
• When combining ESR (>27 mm/h), CRP (>0.93 mg/L), and fibrinogen (>432 mg/dL), achieving abnormality in at least 2 of 3 tests yields 93% sensitivity and 100% specificity for PJI 1, 2
• The American Academy of Orthopaedic Surgeons strongly recommends using ESR, CRP, and serum interleukin-6 together for optimal diagnostic accuracy in suspected PJI 1, 2

Critical Limitation: False-Negative Rates in Low-Grade Infections

A major pitfall is that 23-32% of culture-positive PJIs present with normal CRP levels, particularly chronic and low-grade infections caused by coagulase-negative staphylococci and Propionibacterium acnes 3. This means:

• Normal inflammatory markers cannot exclude PJI, especially when pain is the only presenting symptom 2, 3
• Per AAOS and MSIS criteria relying heavily on CRP/ESR, nearly one-quarter of actual infections would be missed 3
• Joint aspiration with synovial fluid analysis must be performed even when CRP and ESR are normal if clinical suspicion exists 2

Post-Operative Monitoring Timeline

After uncomplicated total hip or knee arthroplasty, inflammatory markers follow predictable patterns 4:

• CRP peaks on postoperative day 3, then normalizes within 2-4 weeks 1, 4
• ESR peaks around day 3 but remains elevated for up to 3 months postoperatively 4
• CRP persistently elevated beyond 2 months postoperatively strongly suggests infection 1
• Obtain baseline CRP and ESR, then recheck at 2-4 week intervals during active treatment 1, 5

Diagnostic Algorithm for Suspected PJI

1. Order both ESR and CRP simultaneously at presentation - they provide complementary information with CRP rising/falling rapidly (12-24 hours) while ESR remains elevated longer 1, 6

2. Add interleukin-6 testing - provides higher predictive value than ESR or CRP alone, with excellent sensitivity when combined with CRP 1, 2, 5

3. Proceed immediately to joint aspiration regardless of inflammatory marker results if clinical suspicion exists 2:

   • Withhold antibiotics for at least 2 weeks prior to aspiration when clinically feasible 2, 5
   • Synovial fluid alpha-defensin achieves 97% sensitivity and 96% specificity 5
   • When combined with synovial CRP, specificity increases to 100% 5

4. Obtain radiographs first to evaluate for loosening, osteolysis, or component migration 2

Special Population: Inflammatory Arthritis Patients

ESR and CRP remain useful even in patients with underlying inflammatory arthritis, though interpretation requires caution 7:

• In two-stage revision arthroplasty for PJI, ESR and CRP decreased significantly between stages in non-infected patients (mean ESR decrease 31.6 mm/h, mean CRP decrease 5.2 mg/dL) but remained elevated in persistently infected patients 7
• Optimal thresholds for persistent infection: ESR >29.5 mm/h (64% sensitivity, 77% specificity) and CRP >2.8 mg/dL (64% sensitivity, 90% specificity) 7
• CRP maintains 90% specificity even in inflammatory arthritis patients, making it reliable for ruling in infection 7

Role in Non-Infectious Orthopaedic Conditions

Osteoarthritis

ESR and CRP are typically normal or only mildly elevated in non-erosive osteoarthritis and are not required for diagnosis 8:

• Blood tests should be reserved for excluding coexistent inflammatory arthropathy when atypical features are present 8
• More pronounced elevations warrant investigation for alternative diagnoses such as rheumatoid arthritis, psoriatic arthritis, or gout 8

Inflammatory Arthritis Monitoring

ESR should be measured at baseline and repeated at 1-3 month intervals during active disease, then every 3-6 months once remission is achieved 1:

• ESR is incorporated into DAS28-ESR composite scores for rheumatoid arthritis disease activity assessment 1
• Higher baseline ESR values indicate greater disease severity and identify patients requiring early DMARD therapy 1
• Anemia, azotemia, elevated immunoglobulins, and rheumatoid factor can artificially elevate ESR independent of inflammatory activity 1

CRP vs ESR: When to Use Which Test

Use CRP Preferentially For:

• Acute infections and septic arthritis - rises within 12-24 hours, peaks at 48 hours 1, 6
• Monitoring early treatment response - normalizes within weeks, making it superior for detecting therapeutic efficacy 1, 6
• Prosthetic joint infections - less affected by confounding factors like anemia and azotemia 1
• Patients on NSAIDs - though NSAIDs can suppress CRP more than ESR 1

Use ESR Preferentially For:

• Chronic inflammatory conditions - fibrinogen (measured indirectly by ESR) has longer half-life than CRP 6
• Giant cell arteritis screening - ESR >40 mm/h has 93.2% sensitivity with negative likelihood ratio of 0.18 1
• Polymyalgia rheumatica monitoring - ESR >40 mm/h associated with higher relapse rates 1

Critical Interpretation Caveats

• No significant correlation exists between extremely elevated ESR and CRP levels - they measure different aspects of inflammation 1
• ESR remains elevated longer after inflammation resolves, creating potential discordance with CRP 1
• Peripheral WBC counts are not elevated in most prosthetic joint infections, making normal WBC meaningless for excluding infection 2
• Women have higher baseline ESR values than men, and ESR normally increases with age 1
• Obesity itself can cause elevated CRP without underlying inflammatory disease 1

Common Pitfalls to Avoid

1. Never rely on normal ESR/CRP to exclude PJI - up to 32% of culture-positive infections have normal inflammatory markers 3

2. Do not interpret isolated inflammatory marker elevations without clinical context - pain characteristics matter: night pain/rest pain suggests infection while weight-bearing pain suggests mechanical loosening 2

3. Avoid premature joint aspiration in patients on antibiotics - wait at least 2 weeks off antibiotics when clinically feasible to maximize culture yield 2, 5

4. Do not order MRI routinely if clinical and laboratory response to treatment is favorable 1

5. Remember that CRP and ESR correlate poorly with clinical disease activity measures in routine rheumatology practice - they are weak markers of subjective symptoms 9