What does a high sedimentation rate (sed rate) indicate?

What Does a High Sedimentation Rate Indicate?

A high erythrocyte sedimentation rate (ESR) is a nonspecific marker of inflammation that most commonly indicates infection (33% of cases), followed by malignancy (17%), renal disease (17%), and inflammatory disorders (14%) when markedly elevated (≥100 mm/h). 1

Understanding ESR as an Inflammatory Marker

ESR measures blood viscosity and serves as a surrogate marker of systemic inflammation—higher rates indicate increased inflammatory activity in the body. 2 The test reflects elevated levels of acute-phase proteins, particularly fibrinogen, which cause red blood cells to aggregate more readily. 3

Normal vs. Elevated Values

• Normal thresholds: ESR >20 mm/h in men and >30 mm/h in women is generally considered elevated 4
• Moderate elevation: 50-100 mm/h suggests significant underlying disease 4
• Marked elevation: ≥100 mm/h has 90% positive predictive value for an identifiable pathologic cause 1

Primary Disease Categories Associated with Elevated ESR

Infections (Most Common Cause)

Bacterial infections are the leading cause of marked ESR elevation, accounting for 33% of cases with ESR ≥100 mm/h. 1 Specific infectious conditions include:

• Osteomyelitis: ESR ≥70 mm/h has 81% sensitivity and 80% specificity for bone infection in diabetic foot infections 2, 4
• Spinal infections (vertebral osteomyelitis, discitis): Present with persistent nighttime pain, fever, and localized tenderness, particularly in children aged 2-12 years 3
• Endocarditis: Should be considered in patients with fever, heart murmurs, and elevated ESR 4
• Myocarditis: May present with recent viral illness, chest pain, and elevated ESR alongside cardiac troponin elevation 3

Malignancy (Second Most Common)

Malignant neoplasms account for 17% of markedly elevated ESR cases, though sensitivity is only 25% (meaning most cancer patients do not have ESR ≥100 mm/h). 1 The specificity is high at 96%, making extreme elevation suggestive but not diagnostic. 1

Inflammatory/Autoimmune Disorders

Inflammatory conditions account for 14% of marked ESR elevations. 1 Key rheumatologic conditions include:

• Giant cell arteritis (GCA): ESR >40 mm/h has 93.2% sensitivity; ESR >100 mm/h has 92.2% specificity with positive likelihood ratio of 3.11 4
• Polymyalgia rheumatica (PMR): ESR >40 mm/h is associated with higher relapse rates 4
• Rheumatoid arthritis: ESR is incorporated into DAS28-ESR disease activity scores, though it has limited diagnostic value 4, 5
• Systemic lupus erythematosus: High ESR (with low CRP) can occur, particularly during disease flares 3
• Adult-onset Still's disease: Typically presents with markedly elevated ESR alongside fever, rash, and arthralgia 2

Cardiovascular Conditions

• Acute rheumatic fever: ESR >60 mm/h is a minor diagnostic criterion 2, 4
• Acute pericarditis: Elevated ESR and CRP support diagnosis 2, 4
• Kawasaki disease: ESR commonly reaches ≥100 mm/h in pediatric patients 2, 4

Renal Disease

Renal disorders account for 17% of markedly elevated ESR cases. 1 Azotemia itself can artificially elevate ESR independent of inflammation. 4

Clinical Approach to Elevated ESR

When ESR is Most Diagnostically Useful

Temporal arteritis/GCA is the condition where ESR has the greatest diagnostic utility—it is the most useful application of this test. 5 An ESR >40 mm/h in a patient with new-onset localized headache, jaw claudication, or visual symptoms warrants urgent specialist referral. 4

When ESR Has Limited Value

• Screening asymptomatic patients: ESR is not useful as a screening test in persons without symptoms 5
• Excluding disease: Normal ESR does not rule out cancer, infection, or connective tissue disease 5
• Early malignancy detection: Only 8.5% of outpatients with elevated ESR have malignancy; it is not an early tumor marker 6

Factors That Artificially Elevate ESR

• Anemia: Decreases blood viscosity, increasing ESR 4
• Female gender: Women have higher baseline values 4
• Advanced age: ESR normally increases with aging 4
• Azotemia/renal dysfunction: Elevates ESR independent of inflammation 4
• Hypergammaglobulinemia: Increases rouleaux formation 4

Diagnostic Workup Strategy

When encountering elevated ESR, focus on:

1. Assess for GCA/PMR symptoms: New headache, jaw claudication, visual changes, bilateral shoulder/hip girdle pain with morning stiffness >45 minutes 4

2. Obtain complementary inflammatory markers: Measure CRP, which rises and falls more rapidly than ESR and provides complementary information 2, 7

3. Complete blood count: Evaluate for anemia, leukocytosis, or thrombocytosis 4

4. Targeted evaluation based on symptoms: Rather than extensive investigation, let clinical presentation guide workup 5, 6

5. Consider temporal pattern: If ESR elevation is unexplained, repeat in 2-4 weeks—transient elevations are common and rarely indicate serious disease 4, 5

Key Clinical Pearls

• Specificity exceeds sensitivity: An ESR ≥100 mm/h has >99% specificity as a "sickness index" but low sensitivity (21-36%) for specific diseases 1
• CRP vs. ESR timing: CRP normalizes faster than ESR during inflammation resolution, making CRP better for monitoring acute treatment response 2, 7
• Unexplained elevation: In patients discharged with "elevated ESR of unknown origin," only 5.3% developed malignancy during 5-year follow-up 6
• Avoid extensive investigation: Without suggestive symptoms, extensive workup for elevated ESR is low-yield and potentially harmful 6