What causes an elevated Erythrocyte Sedimentation Rate (ESR)?

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Last updated: May 19, 2025View editorial policy

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From the Guidelines

Elevated erythrocyte sedimentation rate (ESR) is primarily caused by inflammation in the body, which can be due to various factors such as infections, autoimmune disorders, cancers, tissue injury, or trauma, as supported by the most recent study 1. When inflammation occurs, the liver produces proteins called acute phase reactants, particularly fibrinogen, which cause red blood cells to stick together and form stacks called rouleaux. These heavier stacks settle more quickly in a test tube, resulting in a higher ESR value. Some common causes of elevated ESR include:

  • Infections (bacterial, viral, or fungal)
  • Autoimmune disorders (like rheumatoid arthritis, lupus, or inflammatory bowel disease)
  • Cancers (especially multiple myeloma)
  • Tissue injury or trauma
  • Chronic inflammatory conditions Age and pregnancy can also naturally increase ESR levels. The degree of elevation often correlates with the severity of inflammation, with very high levels (>100 mm/hr) suggesting serious conditions like infections, malignancies, or severe autoimmune diseases, as indicated in the study 1. It's essential to note that ESR is a non-specific marker that indicates inflammation is present somewhere in the body but doesn't identify the specific location or cause, so additional diagnostic tests are typically needed to determine the underlying condition, as recommended in the guideline 1. In clinical practice, a high ESR value should prompt further investigation to determine the underlying cause of inflammation, and management should focus on addressing the underlying condition to reduce morbidity, mortality, and improve quality of life, as emphasized in the study 1.

From the Research

Causes of Elevated ESR

Elevated erythrocyte sedimentation rate (ESR) can be caused by various factors, including:

  • Inflammatory conditions, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) 2, 3
  • Infections, which can increase ESR levels 4, 5
  • Chronic inflammatory diseases, which can lead to discrepancies between ESR and C-reactive protein (CRP) measurements 5
  • Noninfectious conditions, such as osteoarthritis (OA) 3
  • Physiological factors, including resolution of inflammation, which can contribute to abnormally high ESR/low CRP readings or vice versa 5
  • Elevated serum globulin gap, which is a highly reliable marker of elevated ESR in patients with systemic rheumatic diseases 6

Factors Affecting ESR Measurements

Several factors can affect ESR measurements, including:

  • Fibrinogen levels, which have a longer half-life than CRP, making ESR helpful in monitoring chronic inflammatory conditions 4
  • White blood cell count, SLE duration, sex, race, and age, which can influence the ratio of ESR to CRP 2
  • Albumin-to-globulin (A:G) ratio, which can correlate with ESR and CRP levels 6

Clinical Relevance of ESR

ESR is a widely used laboratory marker of systemic inflammation, but it lacks sensitivity and specificity, and should be used only in combination with clinical history and physical exam for diagnosis and monitoring of pathological conditions 5. The clinical application of ESR is best applied to conditions in which there is high or low clinical probability of disease 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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