How soon can a C-Reactive Protein (CRP) test be repeated if the initial result is elevated and the erythrocyte sedimentation rate (ESR or sed rate) is normal, and what are the causes of elevated CRP?

Timing for Repeat CRP Testing and Causes of Elevated CRP

When CRP is elevated and ESR is normal, the CRP test should be repeated after 2 weeks to confirm the result and monitor changes in inflammation levels. 1

Timing for Repeat CRP Testing

The CDC/AHA guidelines recommend the following approach for CRP testing:

• For metabolically stable patients, two measurements should be taken, optimally 2 weeks apart, and the results averaged 1
• If CRP level is ≥10 mg/L, the test should be repeated after examining for sources of infection or inflammation 1
• In patients with elevated biomarkers of inflammation but in symptomatic remission (such as in ulcerative colitis), repeat measurement in 3-6 months may be reasonable 1

Causes of Elevated CRP

CRP is an acute-phase reactant that increases in response to various inflammatory conditions. Common causes include:

Cardiovascular Conditions

• Myocardial infarction 2
• Venous thromboembolism 2
• Atherosclerosis 1

Infectious Diseases

• Urinary tract infections 2
• Gastrointestinal infections 2
• Pulmonary infections 2
• Bloodstream infections/sepsis 2
• Osteomyelitis 3

Inflammatory Disorders

• Inflammatory bowel disease 1
• Rheumatoid arthritis 1, 4
• Some connective tissue diseases 2

Post-surgical States

• CRP typically rises after surgery and returns to baseline within 2-3 weeks in uncomplicated cases 1, 5
• Persistent elevation beyond 3 weeks may indicate complications such as infection 5

Other Causes

• Long-term alcoholism 1
• Obesity
• Advanced age
• Smoking

CRP/ESR Discordance

When CRP is elevated but ESR is normal (discordance), potential explanations include:

1. Different time courses: CRP rises and falls more rapidly than ESR during inflammatory processes 3
2. Type of inflammation: Certain infections (particularly urinary, gastrointestinal, pulmonary, and bloodstream) tend to cause high CRP with normal ESR 2
3. Acute vs. chronic inflammation: CRP responds more to acute inflammation while ESR may better reflect chronic inflammation
4. Low albumin states: Associated with both types of discordance 4
5. Fluctuations around upper limits of normal: Minor variations can cause apparent discordance 3

Clinical Implications and Approach

When faced with elevated CRP and normal ESR:

1. Assess for acute infection or inflammation

   • Focus on urinary tract, gastrointestinal, pulmonary, and bloodstream infections 2
   • Consider myocardial infarction or venous thromboembolism 2

2. Consider timing

   • CRP rises within 4-6 hours of inflammatory stimulus and peaks at 24-48 hours
   • ESR rises more slowly and may take longer to normalize

3. Repeat testing after 2 weeks 1

   • If CRP normalizes, the inflammation was likely transient
   • If CRP remains elevated, further investigation is warranted

4. If CRP ≥10 mg/L

   • Examine for obvious sources of infection or inflammation 1
   • Repeat the test after addressing any identified causes

Pitfalls and Caveats

• CRP/ESR discordance occurs in approximately 12-33% of patients 3, 6, 2
• In hospital practice, CRP is generally more informative and sensitive than ESR for detecting inflammation 6
• When evaluating inflammation, priority should be given to CRP over ESR due to ESR's slower variation and frequent confounding factors 6
• Normal CRP with elevated ESR is more common in lupus, stroke/TIA, and some bone/joint infections 2
• CRP results should be expressed in mg/L to one decimal point 1

Remember that both tests have limitations, and clinical context should always guide interpretation and management decisions.