Inflammatory Markers

Indications for Testing

Inflammatory processes are a component of a wide range of diseases. CRP, ESR, and PCT are general, nonspecific tools that may be useful in specific scenarios. Measurement of inflammatory marker levels can be used in conjunction with a patient’s overall clinical picture to:

• Aid in the diagnosis of certain suspected inflammatory disorders (eg, ESR is useful for giant cell arteritis and CRP for neonatal sepsis)
• Distinguish between inflammatory and noninflammatory diseases (eg, osteoarthritis versus rheumatoid arthritis or inflammatory bowel disease versus irritable bowel syndrome)
• Manage certain antibiotic therapies (eg, PCT measurements can be used to support shortening the duration of antimicrobial therapy in patients with lower respiratory tract infections)
• Predict recovery (eg, PCT levels can be used to predict 28-day cumulative mortality risk for patients diagnosed with sepsis)

Laboratory Testing

Diagnosis

C-Reactive Protein

CRP concentrations are a reliable early indicator of active systemic inflammation because they can help differentiate inflammatory from noninflammatory conditions and reflect the severity of the inflammatory insult.  CRP is recommended over ESR to detect acute phase inflammation in patients with undiagnosed conditions because it is more sensitive and specific than ESR.  CRP has a narrow range of normal values, usually <3-10 mg/L in the blood, but in patients with infections or inflammatory conditions, levels can rise several hundred-fold.   CRP is also a useful measure because concentrations change rapidly within the first 6-8 hours after injury, peak after 48 hours, and return to normal levels once the issue has resolved.  Additionally, some studies indicate that ratios of serial CRP measurements to the CRP level at admission may be associated with outcomes in critically ill patients.  However, in critically ill patients and those in the intensive care unit (ICU), PCT has greater accuracy and may be preferable to CRP, given that the specificity and sensitivity of CRP are lower and peak levels may not correspond to the severity of inflammation.  

High-sensitivity CRP (hsCRP) is not used for the same purposes as CRP and should not be used in the assessment of general inflammatory processes. For recommended uses for this test, see the ARUP Consult Atherosclerotic Cardiovascular Disease Risk Markers topic.

Erythrocyte Sedimentation Rate

ESR is an indirect measurement of plasma protein concentrations and is influenced by a number of disease states. Because the ESR depends on several proteins with varying half-lives, the rate rises and falls more slowly than do CRP concentrations.   Furthermore, normal ESR values are specific to age and sex; the rate increases steadily with age and is higher in women than in men. Although CRP measurements have a clear advantage over ESR values,  the ESR test remains useful in the diagnosis of select conditions, particularly general bone lesions and osteomyelitis. 

Procalcitonin

The release of PCT into the circulation is most often induced by bacterial infection; however, increases can also result from other causes, including severe viral infection, pancreatitis, tissue trauma, and certain autoimmune disorders.   Furthermore, PCT elevations are not usually associated with bacterial colonization, localized bacterial infection, or allergic responses.  In the diagnosis of sepsis, increased PCT levels have a high positive predictive value, and normal levels have a high negative predictive value. 

PCT measurements can also be used to help personalize treatment, manage antibiotic prescriptions, and reduce antibiotic exposure, which has prompted the U.S. Food and Drug Administration (FDA) to approve the use of PCT testing to guide antibiotic use in patients with acute respiratory illnesses. 

Monitoring

Because CRP levels fall quickly once the cause of inflammation has resolved, CRP is a useful marker for monitoring disease activity and response to or need for treatment.  Studies have shown that CRP levels should decrease during the first 48 hours if treatment is adequate; increases in CRP concentrations during the first 48 hours suggest inadequate therapy.  Guidelines recommend waiting at least 24 hours before repeating CRP measurements,  except in neonates, in whom testing is recommended after 18-24 hours.  PCT measurements may provide similarly useful information for treatment decisions and disease monitoring.