What the Erythrocyte Sedimentation Rate Checks For
The erythrocyte sedimentation rate (ESR) is a nonspecific marker of systemic inflammation that measures how quickly red blood cells settle in a test tube, with faster settling indicating the presence of inflammatory proteins in the blood. 1
Primary Clinical Purpose
ESR serves as a surrogate marker of inflammation by measuring blood viscosity, with higher rates indicating increased inflammatory activity in the body. 2 The test works by detecting changes in plasma proteins—particularly fibrinogen—that cause red blood cells to stack together and fall more rapidly. 3
What ESR Actually Detects
Inflammatory conditions: ESR becomes elevated when inflammatory proteins (fibrinogen, immunoglobulins, acute-phase reactants) increase in the blood, causing red blood cells to aggregate and sediment faster. 1, 2
Infection: Bacterial infections including osteomyelitis, septic arthritis, and chronic infections cause significant ESR elevations. 2 In diabetic foot infections, ESR ≥70 mm/h has 81% sensitivity and 80% specificity for underlying osteomyelitis. 1
Autoimmune diseases: ESR is elevated in conditions like giant cell arteritis (where ESR >40 mm/h has 93.2% sensitivity), polymyalgia rheumatica, rheumatoid arthritis, and inflammatory bowel disease. 1, 2
Malignancy: Cancer can elevate ESR, though the test is often normal in many cancer patients and therefore has limited screening value. 4
Tissue injury and necrosis: Any process causing tissue damage triggers inflammatory responses that ESR can detect. 5
Key Clinical Applications
Disease monitoring is where ESR proves most valuable rather than initial diagnosis. 4 The test is particularly useful for:
Giant cell arteritis and polymyalgia rheumatica: ESR should be measured at baseline and repeated every 1-3 months during active disease, then every 3-6 months once remission is achieved. 1 Regular ESR monitoring enables the treat-to-target strategy that improves outcomes. 1
Inflammatory arthritis: ESR is incorporated into validated disease activity measures (DAS28-ESR) for rheumatoid arthritis monitoring. 1 Higher baseline ESR values indicate greater disease severity and help identify patients requiring early aggressive therapy. 1
Kawasaki disease: ESR is often above 40 mm/h and commonly reaches ≥100 mm/h, though CRP may be more accurate after IVIG therapy. 1
Inflammatory bowel disease: ESR correlates with disease activity in ulcerative colitis and can be used alongside calprotectin to monitor disease activity. 2 However, CRP is more sensitive than ESR for evaluating acute abdominal pain in IBD patients. 6
Important Limitations and Pitfalls
ESR is not a screening test and is seldom the sole clue to disease in asymptomatic persons. 4 When using ESR, recognize these critical limitations:
Poor sensitivity: ESR is often normal in patients with cancer, infection, and connective tissue disease, making it unreliable for excluding these diseases. 4 In inflammatory bowel disease, ESR has only 54-78% sensitivity. 7
Nonspecific elevation: An unexplained increase in ESR is generally transitory and seldom due to serious disease. 4 When ESR is elevated, a careful history and physical examination will generally disclose the cause. 4
Confounding factors: Anemia, azotemia, elevated immunoglobulins, and rheumatoid factor can all increase ESR independent of inflammatory activity. 1, 7 Women have higher baseline ESR values than men, and ESR normally increases with age. 1, 7
Slow kinetics: Fibrinogen (for which ESR is an indirect measure) has a much longer half-life than CRP, making ESR less useful for acute diagnosis but better for monitoring chronic inflammatory conditions. 5 The slow rise (48 hours) and fall of ESR relative to other acute-phase reactants makes it superior for monitoring chronic inflammation. 3
Interpretation Thresholds
General screening: ESR values are typically considered elevated when they exceed 20 mm/h in men and 30 mm/h in women. 1
Moderate elevation (50-100 mm/h): More likely to indicate significant underlying disease. 1
High elevation (≥100 mm/h): ESR >100 mm/h has 92.2% specificity for giant cell arteritis with a positive likelihood ratio of 3.11. 1
When ESR and CRP Diverge
If ESR is elevated but CRP is normal, this discordance pattern suggests:
Anemia: Directly increases ESR independent of inflammation. 7
Renal insufficiency: Associated with >3-fold increased risk of this discordance pattern. 7
Age and gender effects: Consider age-adjusted reference ranges as ESR normally increases with advancing age and is higher in women. 7
In this scenario, assess hemoglobin/hematocrit for anemia, measure serum creatinine to check renal function, and repeat ESR and CRP in 2-4 weeks to determine if elevation is persistent or transitory. 7 CRP is the preferred marker for active inflammation because it rises and falls more rapidly with disease activity. 7