What is the erythrocyte sedimentation rate (ESR)?

What is the Erythrocyte Sedimentation Rate (ESR)?

The erythrocyte sedimentation rate (ESR) is a laboratory test that measures how quickly red blood cells settle to the bottom of an upright test tube over one hour, serving as a nonspecific marker of systemic inflammation. 1

Test Methodology and Mechanism

The test involves placing anticoagulated whole blood into an upright tube and monitoring the rate at which red blood cells fall over time. 1 The underlying physics is straightforward:

• Red blood cells normally repel each other due to negative surface charges that prevent them from sticking together. 1
• When inflammation is present, plasma proteins (particularly fibrinogen) neutralize these charges, allowing red blood cells to stack into chains called "rouleaux," which fall more rapidly due to their increased mass. 1, 2
• The Westergren method is the most commonly used technique for performing the ESR. 1

Normal Values and What Constitutes Elevation

ESR values are typically considered elevated when they exceed 20 mm/h in men and 30 mm/h in women. 3 However, interpretation requires nuance:

• Moderate elevation (50-100 mm/h) is more likely to indicate significant underlying disease. 3
• Extreme elevation (≥100 mm/h) has the highest specificity (92.2%) for serious conditions like giant cell arteritis. 3
• Women have higher baseline ESR values than men, and ESR normally increases with advancing age. 3, 4

Clinical Utility: Where ESR Actually Helps

The ESR is not a useful screening test in asymptomatic persons and is seldom the sole clue to disease. 5 However, it excels in specific clinical scenarios:

Definitive Diagnostic Value

• Giant cell arteritis: An ESR >40 mm/h has 93.2% sensitivity with a negative likelihood ratio of 0.18. 3
• Polymyalgia rheumatica: ESR >40 mm/h is associated with higher relapse rates and helps guide treatment decisions. 3
• Kawasaki disease: ESR is often above 40 mm/h and commonly reaches ≥100 mm/h. 3

Monitoring Chronic Inflammatory Conditions

ESR is superior to other markers for monitoring chronic inflammation because it rises slowly (over 48 hours) and falls slowly, making it ideal for tracking disease activity over time. 1, 6 This contrasts with C-reactive protein (CRP), which rises and falls rapidly. 6

• Rheumatoid arthritis: ESR is incorporated into DAS28-ESR disease activity scores and should be measured every 1-3 months during active disease, then every 3-6 months in remission. 3
• Inflammatory bowel disease: ESR has limited utility with sensitivity of only 54-78% for discriminating organic from functional disease. 7

Factors That Artificially Alter ESR

Multiple non-inflammatory factors can elevate or depress ESR, creating diagnostic confusion:

Factors That Increase ESR

• Anemia directly increases ESR independent of inflammation. 3, 4
• Azotemia/renal insufficiency is associated with >3-fold increased risk of elevated ESR. 3, 4
• Female sex and advancing age physiologically increase baseline ESR. 3, 4
• Elevated immunoglobulins and rheumatoid factor can increase ESR independent of inflammatory activity. 3

Technical Factors

• Temperature, time from specimen collection, tube orientation, and vibration can all affect results. 1
• Red blood cell size, shape, and concentration impact the sedimentation rate. 1

ESR vs. CRP: When to Use Which Test

CRP is the preferred marker for active inflammation because it rises and falls more rapidly with disease activity, making it superior for diagnosing acute conditions and monitoring response to therapy. 4, 6 In contrast:

• ESR remains elevated longer than CRP after inflammation resolves, which can create discordance between the two tests. 4
• Fibrinogen (for which ESR is an indirect measure) has a much longer half-life than CRP, making ESR more useful for monitoring chronic inflammatory conditions. 6
• When ESR is elevated but CRP is normal, consider anemia, renal insufficiency, or that inflammation is resolving (ESR lags behind CRP). 4

Critical Limitations and Common Pitfalls

The ESR is often normal in patients with cancer, infection, and connective tissue disease and is therefore of little use in excluding these diseases in patients with vague complaints. 5 Additional caveats:

• Do not use ESR as a screening test to identify patients who have serious disease—this is not supported by the literature. 8
• An unexplained increase in ESR is generally transitory and seldom due to serious disease when history and physical examination are unrevealing. 5
• Repeat the test in 2-4 weeks rather than pursuing an exhaustive search for occult disease when ESR is mildly elevated without clear explanation. 3, 8
• Extreme elevation (≥100 mm/h) is strongly associated with serious underlying disease, most often infection, collagen vascular disease, or metastatic malignancy. 8