How do you interpret elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) results in a patient?

Interpreting ESR and CRP in Clinical Practice

Direct Interpretation Framework

ESR and CRP are complementary inflammatory markers that should be interpreted together, with CRP being the superior marker for acute inflammation because it rises and falls more rapidly with disease activity, while ESR remains elevated longer and is influenced by non-inflammatory factors including anemia, renal disease, age, and sex. 1, 2

Normal Reference Values

• ESR thresholds: >20 mm/h in men and >30 mm/h in women indicate elevation 1, 3
• CRP threshold: >5-6 mg/L is typically considered elevated 3
• Moderate ESR elevation: 50-100 mm/h suggests significant underlying disease 1
• Highly elevated ESR: ≥70 mm/h has 81% sensitivity and 80% specificity for osteomyelitis in diabetic foot infections 1
• Women have higher baseline ESR values than men, and ESR normally increases with age 1, 3

Key Interpretation Patterns

Pattern 1: Both ESR and CRP Elevated

This pattern indicates active inflammation and warrants immediate evaluation for:

• Giant cell arteritis (GCA): ESR >40 mm/h has 93.2% sensitivity with negative likelihood ratio of 0.18; ESR >100 mm/h has 92.2% specificity with positive likelihood ratio of 3.11 1
• Prosthetic joint infection: When at least 2 of 3 tests (ESR >27 mm/h, CRP >0.93 mg/L, fibrinogen >432 mg/dL) are abnormal, sensitivity is 93% and specificity is 100% 4, 1
• Acute infections: Bacterial infections including osteomyelitis, septic arthritis, and endocarditis cause significant elevations of both markers 1, 5
• Kawasaki disease: ESR often >40 mm/h and commonly ≥100 mm/h 1
• Acute pericarditis: Both markers are commonly elevated 1, 5

Pattern 2: Elevated ESR with Normal CRP

This discordant pattern requires systematic evaluation because ESR elevation may reflect non-inflammatory factors rather than active disease:

Step 1: Check for confounding factors 3

• Measure hemoglobin/hematocrit—anemia directly increases ESR independent of inflammation 3
• Measure serum creatinine and calculate GFR—renal insufficiency/azotemia increases risk of this pattern >3-fold 3
• Consider age and sex—women and elderly patients have higher baseline ESR values 3

Step 2: Confirm CRP is truly normal

• Verify CRP threshold used (typically <5-6 mg/L) 3
• Remember that CRP normalizes faster than ESR during inflammation resolution, so this pattern may represent resolving inflammation 1, 5

Step 3: Consider specific diagnoses 3

• Polymyalgia rheumatica: Evaluate for bilateral shoulder/hip girdle pain with morning stiffness >45 minutes
• Giant cell arteritis: If ESR >40 mm/h with new headache, jaw claudication, or visual symptoms (93.2% sensitivity)
• Occult malignancy or chronic infection: If constitutional symptoms present (fever, weight loss, night sweats)

Step 4: Repeat testing

• Repeat ESR and CRP in 2-4 weeks to determine if elevation is persistent or transitory 1, 3

In systemic lupus erythematosus (SLE) patients with fever, each unit increase in the ESR:CRP ratio is associated with 17% increased odds of SLE flare versus infection (OR 1.17,95% CI 1.04-1.31), making a higher ratio more suggestive of flare than infection. 6

Pattern 3: Normal ESR with Elevated CRP

This pattern indicates acute inflammation and CRP should be trusted as the more accurate marker:

• CRP is a direct acute-phase reactant that rises and falls rapidly with active inflammation, independent of ESR 1
• This pattern is typical of early or acute inflammatory processes before ESR has time to rise 2

Pattern 4: Elevated ESR with Normal WBC

This pattern requires evaluation for: 5

• Adult-onset Still's disease: Markedly elevated ESR with fever, rash, arthralgia, and elevated ferritin
• Chronic infections: Osteomyelitis, fracture-related infection, or atypical infections including COVID-19 (mean ESR 29.3 mm/h with normal WBC)
• Viral infections: Can produce elevated ESR with normal WBC counts

Disease-Specific Monitoring Applications

Rheumatoid Arthritis

• ESR and CRP are incorporated into DAS28-ESR and DAS28-CRP disease activity scores, though they are not interchangeable 1
• Measure ESR every 1-3 months during active disease until remission, then every 3-6 months in remission 1
• CRP is the preferred marker because it responds more quickly to changes in disease activity 7, 2
• When ESR and CRP are discordant (28% of cases), CRP is the better measure of disease activity 7

Polymyalgia Rheumatica/Giant Cell Arteritis

• ESR is the most useful laboratory parameter for assessing PMR/GCA 8
• ESR was raised (>30 mm/h) in 100% of cases before treatment, while CRP was raised in 89% 8
• During relapses, ESR was normal in 48% and CRP in 56% of cases, indicating both can miss active disease 8
• ESR >40 mm/h is associated with higher relapse rates in PMR patients 1

Prosthetic Joint Infection

• CRP has sensitivity of 73-91% and specificity of 81-86% for prosthetic knee infection when cutoff of 13.5 mg/L is used 4
• CRP generally returns to baseline within 2 months after surgery under normal circumstances 4
• The American Academy of Orthopaedic Surgeons strongly recommends ESR, CRP, and serum interleukin-6 testing for patients being assessed for periprosthetic joint infection 4

Inflammatory Bowel Disease

• ESR correlates with disease activity in ulcerative colitis 5
• Do not use ESR to screen for IBD—sensitivity is only 54-78% and specificity 46-95% 5, 3

Critical Pitfalls to Avoid

1. Never rely on ESR alone for acute inflammation—CRP is more sensitive and responds more quickly to changes 2

2. Recognize non-inflammatory causes of elevated ESR: anemia, azotemia, elevated immunoglobulins, rheumatoid factor, female sex, and older age all increase ESR independent of inflammation 1, 7

3. In SLE patients, normal CRP does not exclude flare—ESR may be more useful in this population, and the ESR:CRP ratio helps distinguish flare from infection 6, 2

4. False negatives occur frequently—during PMR/GCA relapses, ESR was normal in 48% and CRP in 56% of cases 8

5. Partial correlation analysis shows that substantial portions of ESR correlation with disease activity are explained by immunoglobulins, rheumatoid factor, and hemoglobin rather than acute phase response 7

6. In rheumatoid arthritis, ESR and CRP correlate weakly with clinical disease activity measures (average correlation 0.248 for ESR and 0.259 for CRP) 9, 7