What are the reasons for an elevated Erythrocyte Sedimentation Rate (ESR)?

Causes of Elevated Erythrocyte Sedimentation Rate (ESR)

An elevated ESR is primarily caused by inflammatory conditions, infections, malignancies, and certain hematological disorders, with the degree of elevation often correlating with disease severity.

Common Causes of ESR Elevation

Inflammatory Conditions

• Autoimmune diseases:
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Adult-onset Still's disease (AOSD) 1
  • Polymyalgia rheumatica (most common new-onset rheumatic disease causing elevated ESR) 2
  • Temporal arteritis/Giant cell arteritis
  • Vasculitis

Infections

• Bacterial infections:

  • Pulmonary infections (account for 58% of infectious causes of extremely elevated ESR) 3
  • Osteomyelitis
  • Septic arthritis (ESR elevated in 90% of serious orthopedic infections) 4
  • Endocarditis
  • Periprosthetic joint infections 1

• Viral infections:

  • Kawasaki disease (ESR often elevated above 40 mm/hr, sometimes reaching 100 mm/hr) 1
  • COVID-19 related multisystem inflammatory syndrome in children (MIS-C) 1

Malignancies

• Multiple myeloma
• Lymphoma
• Metastatic cancers
• Hodgkin's disease

Hematological Disorders

• Anemia (can cause false elevation)
• Hypergammaglobulinemia
• Hematopoietic stem cell diseases 3
• Lymphocyte and plasma cell diseases 3

Other Causes

• Renal failure
• Pregnancy
• Advanced age (ESR normally increases with age)
• Recent surgery or trauma (can remain elevated for up to 6 months) 4
• Tissue injury

Degree of ESR Elevation and Clinical Significance

Mild to Moderate Elevation (20-70 mm/hr)

• Mild infections
• Inflammatory conditions in early stages
• Anemia
• Pregnancy
• Advanced age

Marked Elevation (>70 mm/hr)

• Severe infections
• Active autoimmune diseases
• Malignancies
• Temporal arteritis/polymyalgia rheumatica
• Diabetic foot infections (ESR ≥70 mm/hr has sensitivity of 81% and specificity of 80% for diabetic foot osteomyelitis) 1

Extreme Elevation (≥100 mm/hr)

• Has a 90% predictive value for serious underlying disease 5
• Most commonly associated with:
  • Infections (36.6%)
  • Hematological diseases (29.6%)
  • Autoimmune diseases (17.2%) 3

Factors Affecting ESR Interpretation

Physiological Factors

• Age (ESR increases with age)
• Gender (typically higher in females)
• Pregnancy (elevated during normal pregnancy)

Pathological Factors That May Cause False Results

• False elevation:

  • Anemia (decreased RBC count correlates with higher ESR) 3
  • Hypergammaglobulinemia
  • High fibrinogen levels (positive correlation with ESR) 3
  • IVIG therapy (artificially elevates ESR) 1

• False normal or lower values:

  • Polycythemia
  • Sickle cell disease
  • Hypofibrinogenemia
  • Cryoglobulinemia 6

Clinical Pearls

• ESR is a nonspecific marker of inflammation that should be interpreted in clinical context
• Normal ESR after day 7 of illness makes Kawasaki disease unlikely 1
• ESR normalizes more slowly than CRP after resolution of inflammation 1
• CRP is more useful for monitoring response to treatment as ESR can remain elevated longer 1
• ESR should not be used as a screening test in asymptomatic individuals 5
• In patients with nonspecific symptoms and elevated ESR, new-onset rheumatic diseases are the most common cause (52.3%), followed by infections (24.6%) and malignancies (9.2%) 2

Remember that while ESR is a helpful inflammatory marker, it lacks specificity and should be used in conjunction with clinical findings and other laboratory tests like CRP to guide diagnosis and management.