What are Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)?

What are ESR and CRP?

ESR (Erythrocyte Sedimentation Rate) and CRP (C-Reactive Protein) are blood tests that measure inflammation in the body, with CRP being a direct protein marker produced by the liver in response to inflammation, while ESR is an indirect measure reflecting how quickly red blood cells settle in a test tube, influenced by blood viscosity and fibrinogen levels. 1

ESR (Erythrocyte Sedimentation Rate)

Basic Mechanism:

• ESR measures the rate at which red blood cells settle to the bottom of a test tube over one hour, serving as a surrogate marker of inflammation through blood viscosity changes 2
• Higher sedimentation rates indicate increased inflammation, as inflammatory proteins like fibrinogen cause red blood cells to clump together and fall faster 3, 4

Normal Values:

• Men: typically <20 mm/h 5, 6
• Women: typically <30 mm/h (women have higher baseline values than men) 5, 6
• ESR normally increases with age 5

Clinical Interpretation of Elevated Values:

• Moderate elevation (50-100 mm/h) suggests significant underlying disease 5
• ESR >40 mm/h has 93.2% sensitivity for giant cell arteritis 5
• ESR >100 mm/h has 92.2% specificity for serious conditions like giant cell arteritis 5, 6
• ESR >60 mm/h is typical in acute rheumatic fever 2
• ESR >70 mm/h has 81% sensitivity and 80% specificity for osteomyelitis in diabetic foot infections 5, 2

CRP (C-Reactive Protein)

Basic Mechanism:

• CRP is an acute-phase protein synthesized directly by the liver in response to inflammatory cytokines 3, 4
• CRP rises and falls more rapidly than ESR with changes in inflammation, making it more responsive to acute changes 2, 4

Normal Values:

• CRP values >10 mg/L are traditionally considered indicative of significant inflammation 6
• CRP >13.5 mg/L has 73-91% sensitivity and 81-86% specificity for prosthetic joint infection 1, 6

Clinical Characteristics:

• CRP returns to baseline within 2 months after surgery under normal circumstances 1
• CRP normalization is faster than ESR during resolution of inflammation 2
• CRP has a much shorter half-life than fibrinogen (which ESR indirectly measures) 4

Key Differences Between ESR and CRP

Timing and Responsiveness:

• CRP is more useful for diagnosing acute inflammatory conditions and monitoring responses to therapy because it changes rapidly 4
• ESR is better for monitoring chronic inflammatory conditions due to fibrinogen's longer half-life 4
• CRP is more sensitive than ESR for evaluating acute abdominal pain in inflammatory bowel disease patients 1

Factors Affecting Measurements:

• ESR can be artificially elevated by anemia, azotemia, elevated immunoglobulins, and rheumatoid factor independent of inflammatory activity 1, 5
• Women have higher baseline ESR values than men 1, 5, 6
• Low serum albumin affects both ESR and CRP measurements 7

Clinical Applications

When Both Tests Are Used Together:

• In inflammatory bowel disease assessment, both ESR and CRP are recommended as inflammatory biomarkers, though CRP correlates better with endoscopic disease activity in Crohn's disease 1
• For prosthetic joint infection evaluation, both ESR and CRP testing are recommended, with infection unlikely when both are negative 1
• In rheumatoid arthritis, both markers are incorporated into disease activity scores (DAS28-ESR and DAS28-CRP), though they are not interchangeable 5, 6

Common Pitfall - Discordance:

• ESR and CRP show poor agreement (kappa coefficient 0.38) in hospital practice, with discordance occurring in approximately 12-33% of patients 8, 9
• Elevated ESR with normal CRP occurs in 6-28% of cases and may indicate resolving inflammation, renal insufficiency, infection, or confounding factors affecting ESR 8, 7, 9
• Elevated CRP with normal ESR occurs in 1.5-6% of cases and is more common with acute infections (urinary tract, gastrointestinal, lung, bloodstream) and acute vascular events like myocardial infarction 8, 9

Priority in Clinical Use:

• When inflammatory disorder is suspected in unselected patients, priority should be given to CRP due to ESR's slow variation and frequent confounding factors 8
• Both markers lack sufficient sensitivity or specificity when used alone and should always be combined with clinical history and physical examination 3