What are the causes of an elevated Erythrocyte Sedimentation Rate (ESR)?

Causes of Elevated Erythrocyte Sedimentation Rate (ESR)

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

Common Causes of Elevated ESR

Infectious Diseases (Most Common Cause)

• Infections account for approximately 38.6% of extremely elevated ESR cases 2
• Common infectious causes include:
  • Osteomyelitis (6.9% of extreme ESR cases) 2
  • Tuberculosis (5.5%) 2
  • Sepsis (5.1%) 2
  • Urinary tract infections (4.7%) 2
  • Septic arthritis (3.1%) 2
  • Abscesses (2.8%) 2
  • Infective endocarditis 3
  • Pulmonary infections (most common infectious cause in some studies) 4

Autoimmune/Inflammatory Conditions

• Autoimmune diseases account for approximately 15.9% of extremely elevated ESR cases 2
• Common autoimmune/inflammatory causes include:
  • Rheumatoid arthritis (7.3% of extreme ESR cases) 2
  • Polymyalgia rheumatica (most common new-onset rheumatic disease in patients with elevated ESR) 5
  • Giant cell arteritis (ESR >50 mm/hr has sensitivity of 87.5%) 1
  • Systemic lupus erythematosus
  • Vasculitis
  • Inflammatory bowel disease

Malignancies

• Malignancies account for approximately 15.4% of extremely elevated ESR cases 2
• Types include:
  • Lymphoma (5.1% of extreme ESR cases) 2
  • Multiple myeloma
  • Metastatic solid tumors
  • Leukemia
  • Hematologic malignancies (29.6% of extremely elevated ESR in some studies) 4

Renal Diseases

• Renal diseases account for approximately 8.4% of extremely elevated ESR cases 2
• End-stage renal failure (ESRF) patients have a high prevalence of pleural effusions (24.7%) which can contribute to elevated ESR 3
• Uraemic pleuritis 3
• Nephrotic syndrome 3

Tissue Injury or Trauma

• Ischemic tissue injury or trauma accounts for approximately 8.7% of extremely elevated ESR cases 2
• Trauma (5.3% of extreme ESR cases) 2
• Post-surgical states

Other Causes

• Pregnancy (2.2% of extreme ESR cases) 2
• Advanced age (ESR naturally increases with age) 1
• Anemia (ESR has significant negative correlation with RBC count, hemoglobin, and hematocrit) 4
• Hyperfibrinogenemia (ESR positively correlates with fibrinogen levels) 4
• Long COVID and post-viral conditions 3

Significance of ESR Values

Extremely Elevated ESR (≥100 mm/hr)

• Has a 90% predictive value for serious underlying disease 6
• Most often indicates:
  • Infection
  • Collagen vascular disease
  • Metastatic tumor 6
• Represents approximately 4.2% of all ESR tests in some studies 2

Moderately Elevated ESR

• 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
• ESR levels tend to be higher in older patients 4

Clinical Approach to Elevated ESR

1. Consider clinical context

   • ESR should complement, not replace, clinical assessment 1
   • CRP levels may be significantly higher in infections compared to rheumatic diseases or malignancies 5

2. Look for common causes based on ESR level

   • Extremely elevated (≥100 mm/hr): Focus on infections, autoimmune diseases, and malignancies
   • Moderately elevated: Consider broader differential including age-related changes

3. Avoid unnecessary workup

   • ESR should not be used to screen asymptomatic persons for disease 1, 6
   • An isolated elevated ESR without symptoms rarely indicates serious disease 1
   • In asymptomatic persons with markedly elevated ESR, a minimal number of tests usually reveal the cause 6

4. Monitor trends

   • Serial ESR measurements are useful for monitoring disease activity and treatment response 1
   • Consider both ESR and CRP for complementary information 1

Important Caveats

• ESR lacks sensitivity and specificity as a standalone test 6
• Approximately 2.4% of patients with extremely elevated ESR have no identifiable cause 2
• ESR has limited value as an indicator of malignancy in asymptomatic patients 7
• ESR and CRP may not always correlate, particularly in patients on certain treatments like IL-6 receptor blockers 3
• ESR may remain elevated for weeks after resolution of the inflammatory stimulus, while CRP normalizes more quickly 3

By systematically evaluating patients with elevated ESR in the context of their clinical presentation, clinicians can efficiently identify the underlying cause and initiate appropriate management.