What are the causes of an elevated erythrocyte sedimentation rate (ESR) in adults?

Causes of Elevated Erythrocyte Sedimentation Rate

Primary Etiologic Categories

Elevated ESR most commonly results from infections (38.6%), autoimmune/inflammatory diseases (15.9%), malignancies (15.4%), ischemic tissue injury or trauma (8.7%), and renal diseases (8.4%) in adults presenting with markedly elevated values. 1

Infectious Causes

• Bacterial infections are the leading cause of ESR elevation, particularly osteomyelitis (6.9% of cases with ESR ≥100 mm/h), tuberculosis (5.5%), sepsis of unknown origin (5.1%), urinary tract infections (4.7%), septic arthritis (3.1%), and abscesses (2.8%) 1
• Chronic infections including endocarditis should be considered, especially when fever and heart murmurs are present 2
• In diabetic foot infections, ESR ≥70 mm/h has 81% sensitivity and 80% specificity for underlying osteomyelitis 2

Autoimmune and Inflammatory Diseases

• Rheumatoid arthritis is the most common individual autoimmune cause (7.3% of cases with ESR ≥100 mm/h) 1
• Polymyalgia rheumatica is the most frequent new-onset rheumatic disease in patients presenting with unexplained ESR elevation (38% of new-onset rheumatic diseases), particularly when accompanied by bilateral shoulder and hip girdle pain and morning stiffness >45 minutes 3, 4
• Giant cell arteritis should be urgently considered when ESR >40 mm/h (93.2% sensitivity) occurs with new-onset localized headache, jaw claudication, or visual symptoms 2
• Systemic lupus erythematosus, adult-onset Still's disease (characterized by fever, rash, arthralgia), and systemic vasculitis are important considerations 4, 5
• In rheumatoid arthritis patients, persistently elevated ESR is independently associated with worse mortality and indicates active disease requiring treatment adjustment 4

Malignancies

• Malignancy accounts for 15.4% of cases with extremely elevated ESR, with lymphoma representing 5.1% of individual causes 1
• However, ESR is often normal in cancer patients, limiting its utility as a screening test 6
• Extraordinarily high CRP levels (rather than ESR alone) should raise particular suspicion for malignancy, even in patients with known rheumatic disease 3

Tissue Injury and Trauma

• Ischemic tissue injury or trauma causes 8.7% of ESR elevations ≥100 mm/h, with trauma specifically accounting for 5.3% 1
• Acute myocardial infarction and venous thromboembolism can elevate inflammatory markers 2

Renal Diseases

• Renal disease accounts for 8.4% of extremely elevated ESR cases 1
• Azotemia artificially elevates ESR independent of inflammatory activity 2

Hematologic Factors

• Anemia is a critical non-inflammatory cause that artificially elevates ESR 2, 4
• Hypergammaglobulinemia and elevated immunoglobulins increase ESR 2

Pregnancy and Physiologic Factors

• Pregnancy accounts for 2.2% of ESR elevations ≥100 mm/h 1
• Women have higher baseline ESR values than men, and ESR normally increases with age 2
• In healthy elderly persons, ESR may reach 35-40 mm/h without disease 7

Cardiovascular Conditions

• Acute pericarditis commonly presents with elevated ESR alongside chest pain and ECG changes 2, 5
• Acute rheumatic fever typically shows ESR >60 mm/h as a minor diagnostic criterion 5

Inflammatory Bowel Disease

• ESR correlates with disease activity in ulcerative colitis (54-78% sensitivity) and can be used for monitoring alongside fecal calprotectin 5

Pediatric-Specific Causes

• Kawasaki disease shows ESR often >40 mm/h and commonly ≥100 mm/h 2
• Multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 exposure presents with elevated ESR 2, 5

Clinical Interpretation by ESR Level

• ESR >20 mm/h (men) or >30 mm/h (women) is considered elevated and warrants evaluation 2
• ESR 50-100 mm/h indicates moderate elevation with greater likelihood of significant underlying disease 2
• ESR ≥100 mm/h strongly suggests serious pathology, with only 2.4% of cases having no identifiable cause after thorough evaluation 1

Critical Diagnostic Pitfall

In 40% of elderly patients with elevated ESR, multiple diagnoses contribute to the elevation, making single-disease attribution inappropriate 8. The most frequent multifactorial contributors include chronic bronchitis, rheumatoid arthritis, and renal failure 8. A focused evaluation targeting the most likely causes based on clinical presentation is essential, as unexplained transient ESR elevations are generally benign 6.