What are the differences between C‑reactive protein (CRP) and erythrocyte sedimentation rate (ESR)?

CRP vs ESR: Key Differences and Clinical Applications

CRP is the preferred inflammatory marker for acute conditions because it rises and falls rapidly with inflammation (within 12-24 hours), has superior analyte characteristics, and better standardization, while ESR is most valuable for monitoring chronic inflammatory diseases like giant cell arteritis and polymyalgia rheumatica because it remains elevated longer after inflammation onset. 1, 2

Fundamental Biochemical Differences

C-Reactive Protein (CRP)

• Direct acute-phase reactant that rises within 12-24 hours of infection/inflammation onset and peaks at 48 hours 1
• Half-life is significantly shorter than fibrinogen, allowing rapid normalization (within weeks) when inflammation resolves 3
• Better standardization with commercial assays widely available and lower detection limits (0.3 mg/L for high-sensitivity CRP) 1
• Less affected by confounding factors like anemia and azotemia that artificially elevate ESR 1

Erythrocyte Sedimentation Rate (ESR)

• Indirect measure of fibrinogen, which has a much longer half-life than CRP 3
• Remains elevated longer after inflammation resolves, creating potential discordance with CRP 1, 4
• More affected by physiological variables including age, gender (women have higher baseline values), anemia, azotemia, elevated immunoglobulins, and rheumatoid factor 1, 4

Clinical Applications: When to Order Which Test

Order CRP for:

• Acute infections and sepsis - 100% sensitivity and 72% specificity for identifying sepsis in ICU patients when CRP ≥1.5 ng/mL 1
• Prosthetic joint infections - 73-91% sensitivity and 81-86% specificity when cutoff ≥13.5 mg/L 1
• Inflammatory bowel disease monitoring (especially Crohn's disease) - correlates better with endoscopic activity than ESR, with clinically relevant cutoff of 5 mg/L 2
• Cardiovascular risk assessment - obtain 2 measurements 2 weeks apart and average results 2
• Monitoring rapid treatment responses in acute inflammatory conditions 1

Order ESR for:

• Giant cell arteritis diagnosis - ESR >40 mm/h has 93.2% sensitivity with negative likelihood ratio of 0.18; ESR >100 mm/h has 92.2% specificity 1, 2
• Polymyalgia rheumatica monitoring - ESR >40 mm/h predicts higher relapse rates 1, 2
• Rheumatoid arthritis disease activity - contributes 15% of DAS28-ESR calculations 2
• Osteomyelitis in diabetic foot infections - ESR ≥70 mm/h has 81% sensitivity and 80% specificity 1, 2
• Chronic inflammatory disease monitoring - measure every 1-3 months during active disease, then every 3-6 months in remission 1

Order BOTH tests for:

• Initial evaluation of undifferentiated inflammatory arthritis - provides both diagnostic and prognostic information 2
• Prosthetic joint infection workup - when at least 2 of 3 tests (ESR >27 mm/h, CRP >0.93 mg/L, fibrinogen >432 mg/dL) are abnormal, sensitivity is 93% and specificity is 100% 1

Interpretation Thresholds

CRP Risk Categories 2

• Low risk: <1.0 mg/L
• Average risk: 1.0-3.0 mg/L
• High risk: >3.0 mg/L
• If CRP ≥10 mg/L: repeat test and examine for sources of infection or inflammation 2

ESR Elevation Thresholds 1, 2

• Elevated: >20 mm/h in men, >30 mm/h in women
• Moderate elevation: 50-100 mm/h indicates greater likelihood of significant disease
• Highly elevated: ≥100 mm/h is an independent prognostic factor for mortality 1

Understanding CRP/ESR Discordance

Discordance between CRP and ESR occurs in 20-33% of patients and has three main mechanisms: 5

1. Slight fluctuations around upper limits of normal for both tests 5
2. Development of intercurrent illness 5
3. Different time courses - CRP rises and falls faster than ESR, so ESR remains elevated longer after inflammation resolution 1, 5

Common Clinical Scenarios for Discordance:

• High ESR/Normal CRP: Lupus nephritis, chronic osteomyelitis, resolution phase of acute inflammation 5
• High CRP/Normal ESR: Early acute infection (before ESR rises), rheumatoid arthritis in some cases 5
• Recent NSAID use can suppress CRP more than ESR 1
• Immunocompromised patients or neutropenia may have falsely low CRP 1

Critical Clinical Pearls

• Neither marker is sufficiently specific or sensitive when used alone - always combine with clinical history and physical examination 4, 6
• CRP normalizes within 2 months after surgery under normal circumstances, making it useful for detecting postoperative complications 1
• In Kawasaki disease, ESR is often >40 mm/h and commonly ≥100 mm/h, though CRP may be more accurate after IVIG therapy 1
• Obesity itself can cause elevated CRP (and to lesser extent ESR) without underlying inflammatory disease 1
• Only 4 of 14 patients with initial CRP/ESR disagreements had stable discordance on repeat testing over time 5