Markers of Inflammation

I thought today I’d do a little discussion related to two of the more non-specific, questionably useful tests that we have in the laboratory test arsenal, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and their use as markers of inflammation. I’ve left out procalcitonin on purpose since I’ve posted about that inflammatory marker previously. And I won’t discuss hs-CRP and its use in cardiovascular disease risk assessment.

CRP and ESR are referred to as inflammatory markers because both rise when inflammation is present. However neither marker provides much more information other than the presence of inflammation. That leads to the questions: how are these tests useful, and why do we need both?

Good questions! First though, what exactly are these markers? Both of these markers will increase in inflammation, infection and tissue destruction, but at different speeds and to different degrees. CRP is a protein and an acute phase reactant. It is produced by the liver and released in response to inflammatory cytokines, usually within hours of a tissue injury, an infection, or any other cause of inflammation. ESR on the other hand isn’t any kind of analyte at all, but rather a measure of the ability of the red cells to settle out in a blood sample. This settling is affected by the fibrinogen and globulin concentration in the blood as well as by the red cell concentration and how normal the red cells are. Thus besides inflammation, things like anemia, polycythemia and sickle cell disease also will affect an ESR. ESR also increases in malignancies, especially paraproteinemias and other states with abnormal serum proteins, and in autoimmune diseases. ESR elevations are used to support the diagnosis of specific inflammatory diseases, like systemic vasculitis and polymyalgia rheumatic. CRP is useful for monitoring patients after surgery and since it rises rapidly in response to bacterial sepsis, it is often used to monitor response to antimicrobial therapy. Considering the differences in these two “markers” it’s perhaps not surprising that they do not correlate well when compared against each other. Nor is it surprising that the lab has been unable to retire either test.

The pattern of usage for these tests in my lab has shifted in the last several years. In 2007 we ran almost equal numbers of both tests, about 500 per month of each. Eighty percent of the time, both tests were ordered simultaneously. Of those, 20 percent had one normal result and one abnormal result, 50 percent were both abnormal and 30 percent were both normal. Surprisingly, 50 percent of the time, only one single CRP and ESR was ordered, even though these tests are probably more useful when used to trend response and the majority of the time, one or both results were abnormal. This year in 2015 we are running about 1400 CRP per month and 900 ESR per month, and still 70 percent of those ESRs that we do run, are run simultaneously with CRP samples. The same services tend to order both tests, with many of the orders coming from GI, the ED, Orthopedics, Rheumatology, Oncology or Infectious Diseases. CRP tends to be ordered more frequently by general hospitalists, intensivists and Cardiology. ESR orders are STAT 30 percent of the time, while CRP orders are STAT about 22 percent of the time.

Both of these analytes are markers for the presence of an inflammatory process. CRP seems to reflect bacterial or septic processes and response to therapy to a better degree than ESR does, probably because CRP is one of the liver’s acute phase proteins and reflects liver response to injury. CRP also tends to respond more quickly than ESR, rising faster and then falling more rapidly. ESR on the other hand tends to reflect a more systemic response. With either analyte, a one-time order is a snap-shot in time. Thus often one of these markers is normal while the other is abnormal, which may explain why physicians tend to order both. Ordering either analyte as a one-time order will only tell you that inflammation is present, and the results of the tests must always be used in conjunction with other tests and clinical signs and symptoms in order to have any diagnostic efficacy. Sequential CRP or ESR samples allow for trending and helping to determine response to therapy, thus providing more useful information.

-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.

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