Does an elevated erythrocyte sedimentation rate (ESR) indicate acute or chronic inflammation, and what is the most common cause of an elevated ESR?

Elevated ESR Indicates Both Acute and Chronic Inflammation

An elevated ESR is a nonspecific marker that can indicate either acute or chronic inflammation, with the most common causes being infections (particularly bacterial infections like osteomyelitis and septic arthritis), autoimmune/rheumatologic diseases (especially polymyalgia rheumatica and rheumatoid arthritis in adults), and malignancy. 1, 2

Understanding ESR as an Inflammatory Marker

ESR measures blood viscosity and serves as a surrogate marker of inflammation, reflecting the complex of acute phase reactants that increase in various disease states 2. However, ESR is fundamentally a nonspecific sickness index that is not diagnostic of any particular disease 3.

Key Distinction: Acute vs. Chronic Inflammation

ESR remains elevated longer than CRP after inflammation resolves, which creates an important clinical distinction 1:

• For acute inflammation: CRP rises within 12-24 hours and peaks at 48 hours, making it superior for acute presentations 1
• For chronic inflammation: ESR is most valuable for monitoring chronic inflammatory conditions rather than initial diagnosis 1
• Hypergammaglobulinemia and elevated acute-phase reactants (including ESR) are present in a large proportion of patients with chronic conditions like infective endocarditis, particularly when illness duration exceeds 6 weeks 4

Most Common Causes of Elevated ESR

Infections (Primary Cause Category)

Bacterial infections are among the most common causes of significant ESR elevation 1, 2:

• Osteomyelitis: ESR ≥70 mm/h has 81% sensitivity and 80% specificity for diagnosing osteomyelitis in diabetes-related foot infections 1
• Septic arthritis and chronic infections can cause marked elevations 2
• Infective endocarditis: Elevated ESR is a supportive finding, particularly in chronic presentations 4

Rheumatologic/Autoimmune Diseases (Second Major Category)

In adults over 50 years with bilateral shoulder/hip girdle pain and morning stiffness >45 minutes, polymyalgia rheumatica (PMR) is the most likely diagnosis 1:

• Giant cell arteritis (GCA): ESR >40 mm/h has 93.2% sensitivity with negative likelihood ratio of 0.18 1
• Rheumatoid arthritis: ESR is incorporated into disease activity scores (DAS28-ESR) for monitoring 1
• Adult-onset Still's disease: ESR elevation occurs in 95-98% of cases 1

Other Significant Causes

• Malignancy: ESR >100 mm/h is an independent prognostic factor for mortality 1
• Kawasaki disease in children: ESR commonly reaches ≥100 mm/h 1
• Acute rheumatic fever: ESR >60 mm/h is a minor diagnostic criterion 2

Clinical Interpretation Algorithm

Step 1: Determine ESR Level

• Mildly elevated: >20 mm/h (men) or >30 mm/h (women) 1
• Moderately elevated: 50-100 mm/h indicates greater likelihood of significant disease 1
• Markedly elevated: ≥100 mm/h strongly suggests serious pathology (infection, malignancy, GCA, Still's disease) 1

Step 2: Assess Clinical Context

For patients >50 years with new-onset localized headache, jaw claudication, or visual symptoms: Urgent evaluation for GCA is required 1

For bilateral shoulder/hip pain with morning stiffness >45 minutes: Consider PMR, especially if ESR >40 mm/h (associated with higher relapse rates) 1

For fever with elevated ESR: Obtain blood cultures to rule out infective endocarditis, especially if heart murmurs are present 1

Step 3: Obtain Complementary Testing

Measure CRP alongside ESR for optimal diagnostic accuracy 1:

• If CRP is also elevated: Suggests active inflammation requiring urgent workup
• If CRP is normal but ESR elevated: Consider that ESR remains elevated longer after inflammation resolves, or evaluate for conditions affecting ESR independently (anemia, azotemia, elevated immunoglobulins) 1

Complete blood count with differential to assess for anemia, leukocytosis, or thrombocytosis 1

Step 4: Disease-Specific Workup

• If musculoskeletal symptoms: Rheumatoid factor and anti-CCP antibodies 1
• If suspected Still's disease: Serum ferritin (markedly elevated) 1
• If back pain with risk factors: Consider spine infection imaging 1
• If diabetic foot infection: ESR ≥70 mm/h warrants evaluation for osteomyelitis 1

Critical Limitations and Confounding Factors

Anemia and azotemia artificially elevate ESR independent of inflammatory activity 1. Women have higher baseline ESR values than men, and ESR normally increases with age 1.

ESR is often normal in patients with cancer, infection, and connective tissue disease, making it of little use in excluding these diseases in patients with vague complaints 5. It is seldom the sole clue to disease in asymptomatic persons and is not a useful screening test 5.

Monitoring Strategy

For chronic inflammatory conditions: Measure ESR every 1-3 months during active disease until remission, then every 3-6 months once low disease activity is maintained 1. Any increase in ESR should prompt clinical reassessment, as rising inflammatory markers may signal reactivation 1.