What is the workup for an elevated Erythrocyte Sedimentation Rate (ESR)?

Diagnostic Workup for Elevated Erythrocyte Sedimentation Rate (ESR)

The diagnostic workup for an elevated ESR should begin with targeted evaluation for common inflammatory conditions, particularly giant cell arteritis, polymyalgia rheumatica, infections, and malignancies, as these represent the most frequent causes of significantly elevated ESR values. 1

Initial Assessment

• Evaluate for signs and symptoms of giant cell arteritis (GCA), especially in patients with new-onset localized headache, constitutional symptoms, jaw claudication, or visual symptoms, as ESR >40 mm/h has high sensitivity (93.2%) for this condition 1
• Assess for symptoms of polymyalgia rheumatica (PMR), which commonly presents with elevated ESR and is a frequent cause of elevated ESR in elderly patients 1, 2
• Consider infectious causes, particularly osteomyelitis, septic arthritis, and endocarditis, as bacterial infections can cause significant ESR elevations 3, 4
• Screen for malignancy, especially in patients with unexplained weight loss, night sweats, or other constitutional symptoms 5, 2

Laboratory Evaluation

• Obtain complete blood count with differential to assess for anemia, leukocytosis, or other hematologic abnormalities that may contribute to ESR elevation 1
• Measure C-reactive protein (CRP), which often correlates with ESR but may rise and fall more rapidly with changes in inflammation 1, 6
• Consider renal function tests and urinalysis, as nephrotic syndrome and renal insufficiency can cause highly elevated ESR values (near or above 100 mm/h) 7
• In patients with fever, obtain blood cultures to rule out infective endocarditis, especially if heart murmurs are present 4

Imaging Studies

• For patients with non-specific symptoms and significantly elevated ESR (≥50 mm/h) in whom initial evaluation is non-diagnostic, consider PET/CT imaging, which has shown value in identifying underlying causes, particularly large-vessel vasculitis 5
• Echocardiography should be considered in patients with fever and elevated ESR to rule out infective endocarditis, especially in those with S. aureus bacteremia 4
• In patients with back pain and elevated ESR, consider imaging to evaluate for spinal infections, especially in those with risk factors such as IV drug use, diabetes, or immunosuppression 1

Interpretation of ESR Values

• ESR values are typically considered elevated when they exceed 20 mm/h in men and 30 mm/h in women 1
• Moderate elevation (50-100 mm/h) suggests significant underlying disease 1
• Very high ESR values (>100 mm/h) have high specificity (92.2%) for conditions like giant cell arteritis 1
• In diabetic foot infections, ESR ≥70 mm/h has sensitivity and specificity of 81% and 80%, respectively, for diagnosing osteomyelitis 1

Common Pitfalls and Caveats

• ESR can be artificially elevated by anemia and azotemia, which should be considered when interpreting results 1, 6
• Women typically have higher baseline ESR values than men, which should be factored into interpretation 1
• Discrepancies between ESR and CRP measurements are common and may reflect different phases of inflammation or non-inflammatory causes of ESR elevation 6
• Extraordinarily high CRP levels with nonspecific clinical findings should raise suspicion for infection or malignancy, even in patients with known rheumatic diseases 2
• Sample stability for ESR analysis is limited; analysis beyond 4 hours may be unreliable due to sample instability 8