What does an elevated Erythrocyte Sedimentation Rate (ESR) measure indicate?

Elevated Erythrocyte Sedimentation Rate (ESR) Interpretation

An elevated ESR is a non-specific marker of inflammation that indicates the presence of underlying inflammatory conditions, infections, malignancies, or autoimmune disorders, but requires clinical correlation and additional testing to determine the specific cause. 1

What ESR Measures

ESR measures the rate at which red blood cells (erythrocytes) settle in a tube of unclotted blood over a specified time period (usually one hour). The test works because:

• Inflammatory proteins (particularly fibrinogen) cause red blood cells to stack together (rouleaux formation)
• These stacked cells are heavier and fall faster in the tube
• The greater the inflammation, the faster the sedimentation rate

Normal Ranges and Significance

• For low-risk populations: ESR <60 mm/h is considered normal 1
• For moderate to high-risk populations: ESR <30 mm/h is considered normal 1
• In elderly patients: ESR may be as high as 35-40 mm/h even in healthy individuals 2

Clinical Significance of Elevated ESR

Strong Indicators (ESR >70 mm/h)

An ESR ≥70 mm/h is highly suggestive of significant underlying pathology:

• Infections (42% of cases) 3
• Malignancies (27% of cases) 3
• Inflammatory conditions (20% of cases) 3
• Only 5% of markedly elevated ESRs remain unexplained 3

Very High ESR (>100 mm/h)

ESR values exceeding 100 mm/h have a 90% predictive value for serious underlying disease, most commonly:

• Infections
• Collagen vascular diseases
• Metastatic tumors 4

Specific Conditions Associated with Elevated ESR

1. Giant Cell Arteritis/Temporal Arteritis:

   • ESR >100 mm/h has a positive likelihood ratio of 3.11 for GCA 5, 1
   • ESR is particularly useful in diagnosing and monitoring this condition 1

2. Diabetes-Related Foot Infections:

   • ESR ≥70 mm/h has sensitivity of 0.81, specificity of 0.8, and AUC of 0.84 for diabetic foot osteomyelitis 5
   • ESR >60 mm/h plus CRP ≥80 mg/L has high positive predictive value for diabetic foot osteomyelitis 5

3. Inflammatory Bowel Disease:

   • ESR has lower diagnostic accuracy than fecal calprotectin or lactoferrin 5
   • Not recommended as primary screening test for IBD 5

4. Kawasaki Disease:

   • ESR is often elevated to levels not typically found in common viral infections
   • Often above 40 mm/h and sometimes ≥100 mm/h 5
   • Note: IVIG therapy elevates ESR, making CRP more accurate after treatment 5

Limitations of ESR Testing

1. Lacks specificity: ESR is elevated in numerous conditions and cannot differentiate between them 4

2. Limited sensitivity:

   • ESR may be normal despite serious disease 6
   • 26% of patients with malignant disease and 25.6% with non-malignant disease had ESR <20 mm/h 2

3. Not useful for screening: ESR should not be used to screen asymptomatic persons for disease 4, 6

4. Post-surgical considerations:

   • ESR increases after surgery and remains elevated for extended periods
   • After brain tumor surgery, ESR peaks around day 3 and remains elevated up to 10 days 7

Clinical Approach to Elevated ESR

1. Interpret in clinical context:

   • An isolated elevated ESR without symptoms rarely indicates serious disease
   • If unexplained elevated ESR is found, repeat in several months rather than pursuing exhaustive testing 4

2. Consider degree of elevation:

   • Mild elevation: Often non-specific or age-related
   • Moderate elevation (30-70 mm/h): Consider chronic inflammatory conditions
   • Marked elevation (>70 mm/h): Strongly suggests significant underlying pathology 3
   • Very high elevation (>100 mm/h): 90% predictive of serious disease 4

3. Use in combination with other tests:

   • ESR alone has limited diagnostic value
   • Combine with CRP (which responds and normalizes more quickly)
   • For specific conditions, use disease-specific markers in addition to ESR

In summary, while an elevated ESR is a useful indicator of inflammation, its interpretation must always be made in the context of the patient's clinical presentation, and it should be used judiciously rather than as a general screening test.