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Inflammation is the body’s innate response to injury or insult, including infection, trauma, surgery, burns, and cancer. Although there are many inflammatory markers, also known as acute phase reactants, those most commonly measured in clinical practice (and discussed in this topic) are C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT). Because these markers are nonspecific, the tests are not diagnostic for any particular condition, but they may help to identify a generalized state of inflammation along with other tests and aid in the differential diagnosis. Inflammatory markers are also useful in guiding the discontinuation of antibiotic therapy and stratifying mortality risk in patients with sepsis or lower respiratory tract infections. ,
Quick Answers for Clinicians
Besides C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT), other markers of inflammation include serum amyloid A, cytokines, alpha-1-acid glycoprotein, plasma viscosity, ceruloplasmin, hepcidin, and haptoglobin. However, high costs, limited availability, and lack of standardization may limit practical clinical use of markers other than CRP, ESR, and PCT in the evaluation of inflammation. Some acute phase proteins, for example, alpha-1 antitrypsin, fibrinogen and coagulation factors, and complement factors, do serve a role in specific diagnoses.
Many tests, including those used for measuring erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT), have not been fully standardized or harmonized (i.e., the assay and the performance thereof may vary between laboratories, which may lead to significant variation in results ). Thus, inflammatory marker test results require careful interpretation, given that variation in results may lead to inappropriate clinical decision-making and potentially adverse effects on patient care. Repeat testing should be performed using the same assay and laboratory to maximize consistency.
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 and monitoring of certain suspected inflammatory disorders
- Distinguish between inflammatory and noninflammatory diseases (e.g., rheumatoid arthritis versus osteoarthritis or inflammatory bowel disease versus irritable bowel syndrome)
- Differentiate between viral and bacterial causes of infection
- Reduce the duration of antimicrobial therapy in patients with sepsis or lower respiratory tract infections
- Predict recovery (e.g., PCT measurements can be used to predict 28- to 30-day cumulative mortality risk in patients diagnosed with sepsis)
Laboratory Testing
C-Reactive Protein
CRP concentrations are a reliable early indicator of active systemic inflammation and reflect the severity of the inflammatory insult. CRP is recommended over ESR to detect acute phase inflammation in patients with undiagnosed conditions, as CRP is more sensitive and specific than ESR. CRP has a narrow range of normal values, but concentrations can rise several hundredfold in patients with infections or inflammatory conditions. , CRP is 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 inflammation has resolved. Repeated measurements can differentiate between acute inflammation as a result of infection and inflammatory conditions such as systemic lupus erythematosus and rheumatoid arthritis.
PCT has greater accuracy and may be preferable to CRP in critically ill patients and those in the intensive care unit (ICU). , 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, refer to the ARUP Consult Atherosclerotic Cardiovascular Disease Risk Assessment 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 increases and decreases more slowly than 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 are preferred over ESR values in most situations, the ESR test remains useful in the diagnosis of select conditions, particularly general bone lesions and osteomyelitis.
Procalcitonin
PCT is released rapidly into the circulatory system in response to bacterial infection; however, increases can also result from other causes, including severe viral infection, pancreatitis, tissue trauma, and certain autoimmune disorders. , PCT elevations are not usually associated with bacterial colonization, localized bacterial infection, or allergic responses.
Increased PCT concentrations indicate a higher likelihood of bacterial etiology for acute respiratory infections, although a threshold has not yet been established. PCT is also used in the initial workup of sepsis; increased PCT concentrations have a high positive predictive value for progression of severe sepsis or septic shock, whereas normal concentrations have a high negative predictive value.
Monitoring
Because CRP levels decrease 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 for critically ill patients; 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 repeat testing is recommended after 18-24 hours.
PCT measurements should not be used to determine whether to initiate antibiotic therapy in patients with acute respiratory infections or sepsis, but they can be used to help reduce antibiotic therapy duration. , , PCT concentrations may predict mortality in patients with sepsis, and PCT concentrations that have not declined by 80% or more between days 1 and 4 of admission are consistent with higher cumulative mortality risk. ,
ARUP Laboratory Tests
Quantitative Immunoturbidimetry
Quantitative Electrochemiluminescent Immunoassay (ECLIA)
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