What is the clinical significance of an elevated Erythrocyte Sedimentation Rate (ESR)?

Clinical Significance of Elevated Erythrocyte Sedimentation Rate (ESR)

An elevated ESR is a non-specific marker of inflammation that indicates the presence of an underlying inflammatory, infectious, malignant, or autoimmune condition requiring further diagnostic evaluation based on clinical context. 1

Understanding ESR as an Inflammatory Marker

ESR measures the rate at which red blood cells settle in a tube of unclotted blood over one hour. It serves as an indirect measure of fibrinogen and other acute phase reactants in the blood. Normal values vary by age and gender:

• Men: <15 mm/hr (under 50 years), <20 mm/hr (over 50 years)
• Women: <20 mm/hr (under 50 years), <30 mm/hr (over 50 years) 1

Key characteristics of ESR:

• Rises slowly (24-48 hours after onset of inflammation)
• Remains elevated for longer periods (days to weeks)
• Has a longer half-life than CRP, making it more suitable for monitoring chronic inflammatory conditions 2

Clinical Significance of Elevated ESR

Degree of Elevation and Disease Correlation

The magnitude of ESR elevation often correlates with disease severity:

• Markedly elevated ESR (>100 mm/hr): Has a 90% predictive value for serious underlying disease, most commonly:

  • Infection
  • Collagen vascular disease
  • Metastatic malignancy 3

• Moderately elevated ESR:

  • Inflammatory arthritis (e.g., rheumatoid arthritis)
  • Polymyalgia rheumatica
  • Giant cell arteritis (ESR >50 mm/hr is common) 4
  • Prosthetic joint infections (>35 mm/hr) 1
  • Active inflammatory bowel disease (>30 mm/hr) 1

Disease-Specific Applications

1. Infectious Diseases:

   • Elevated in 90% of patients with serious orthopedic infections (discitis, septic arthritis, osteomyelitis) 5
   • Useful in screening for infection in specific settings (orthopedics, pediatrics, gynecology) 3
   • Helpful in diagnosing diabetic foot infections (DFI) - a highly elevated ESR (≥70 mm/hr) has sensitivity of 81% and specificity of 80% for diabetic foot osteomyelitis 4

2. Rheumatologic Conditions:

   • Giant cell arteritis: Pretreatment ESR >50 mm/hr has sensitivity of 87.5% and negative LR of 0.27 4
   • Polymyalgia rheumatica: Typically elevated
   • Rheumatoid arthritis: Used in disease activity monitoring 4, 1

3. Kawasaki Disease:

   • ESR is often markedly elevated (>40 mm/hr, sometimes >100 mm/hr)
   • Note that IVIG treatment elevates ESR; therefore, CRP is more accurate after IVIG therapy 4

4. Suspected Spine Infection:

   • Important laboratory parameter in the diagnostic workup
   • Used alongside CRP, WBC count with differential, and blood cultures 4

5. Malignancy:

   • Limited value as a screening tool for malignancy in asymptomatic patients 6
   • May be useful in monitoring treated Hodgkin's disease 3

Limitations and Caveats

1. Lack of specificity: ESR is affected by many non-inflammatory factors:

   • Age (increases with age)
   • Gender (higher in females)
   • Anemia
   • Pregnancy
   • Medications
   • Plasma protein abnormalities 2

2. False positives: An isolated elevated ESR without symptoms rarely indicates serious disease 1

3. False negatives: A minimally elevated ESR in the setting of severe clinical disease should prompt investigation for disseminated intravascular coagulation 1

4. Screening limitations: ESR should not be used to screen asymptomatic persons for disease 3

Practical Approach to an Elevated ESR

1. Interpret in clinical context:

   • Consider the patient's symptoms, medical history, and other laboratory findings
   • ESR should complement, not replace, clinical assessment 1

2. For asymptomatic patients with unexplained elevated ESR:

   • Repeat the test in several months rather than pursuing an exhaustive search for occult disease 3
   • The prevalence of malignancy in patients with elevated ESR without specific symptoms is low 6

3. For elderly patients with nonspecific health changes:

   • ESR may be useful as a "sickness index" when there is moderate probability of underlying disease 3
   • Consider that multifactorial etiology is common in elderly patients with elevated ESR 7

4. For monitoring disease activity:

   • Serial ESR measurements are valuable for assessing treatment response in chronic inflammatory conditions 1
   • Consider both ESR and CRP for complementary information 2

In summary, while ESR is a simple and inexpensive test, its interpretation requires clinical judgment and consideration of its limitations. When used appropriately, it provides valuable information for diagnosis and monitoring of inflammatory conditions.