Erythrocyte Sedimentation Rate and C-Reactive Protein in Acute Inflammation

Meta-Analysis of Diagnostic Accuracy Studies

Ivana Lapić, MSc; Andrea Padoan, PhD; Dania Bozzato, MSc; Mario Plebani, MD

Disclosures

Am J Clin Pathol. 2019;153(1):14-29. 

In This Article

Abstract and Introduction

Abstract

Objectives: To assess the diagnostic accuracy of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in acute inflammation.

Methods: PubMed and Scopus were searched and eligible articles were screened for methodologic quality using the Quality Assessment of the Diagnostic Accuracy Studies–Revised. Meta-analysis with calculation of pooled sensitivity (Se), specificity (Sp), and summary area under the curve (SAUC) was performed.

Results: Twenty-nine studies were eligible. Se and Sp were 0.78 and 0.68 (SAUC = 0.80) for ESR in orthopedic infections and 0.79 and 0.70 (SAUC = 0.81) for CRP. For the diagnosis of other various inflammatory conditions, CRP had a superior diagnostic accuracy, with a Se of 0.86, Sp of 0.67, and SAUC of 0.86 compared with a Se of 0.77, Sp of 0.59, and SAUC of 0.75 for ESR. Heterogeneity among studies was elevated. Combined use of ESR and CRP yielded higher diagnostic accuracy.

Conclusions: Despite observed heterogeneity among studies, ESR and CRP have a similar diagnostic accuracy in assessment of inflammation, especially in orthopedic conditions.

Introduction

Laboratory testing is widely used in assessment of patients with inflammation inasmuch inflammatory markers are usually determined as part of the initial laboratory screening of patients suspected of having an acute inflammation caused by an underlying specific disease or condition.[1] The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are the most commonly used laboratory tests for detecting the acute phase response and thus diagnosis and monitoring of inflammatory conditions. Despite their lack of disease specificity and influence by several disease factors, they provide valuable information to clinicians in terms of supporting clinical signs and symptoms of inflammation.[2–4]

The sedimentation rate of erythrocytes in plasma is known to be influenced by the level of acute phase proteins, and thus ESR has historically been used as a laboratory test for assessment of acute phase response to inflammation.[5] Since elevation of ESR results from RBC rouleaux formation, for which fibrinogen, the main inductor, is known to be a slow-reacting positive acute phase reactant, ESR's response to inflammation is rather slow and insensitive to minor inflammation. The initial rise occurs within 24 to 48 hours from onset and is followed by a slow fallback after inflammation resolution.[4–6] Moreover, ESR is known to be affected by numerous physiologic and pathophysiologic conditions that involve not only changes of fibrinogen concentration in plasma but also alterations in the size, shape, and/or number of RBCs as well as presence of non–acute phase reaction proteins (eg, immunoglobulins).[4,5,7,8] With the introduction of more sensitive and specific inflammatory biomarkers, ESR has been continuously losing its glory and is being at least coupled with, if not replaced by, other laboratory tests, the most common being CRP.[2,4,5] Therefore, ESR is nowadays considered of limited value for monitoring the onset of acute inflammation, and the use of ESR as a screening test is not recommended.[5] The clinical value of ESR remains useful in assessment of selected clinical conditions. Specifically, diagnostic criteria for rheumatic diseases (rheumatoid arthritis [RA], polymyalgia rheumatica, and giant cell arteritis [GCA]) incorporate ESR as one of the contributors for diagnosis and monitoring of disease progress,[9–11] and published data show that ESR is widely used in predicting and monitoring orthopedic infections.[12]

CRP is also a systematic, nonspecific marker of inflammation and host response to infection with a rather different kinetics and role in the inflammation process compared with ESR. CRP is produced by the liver in response to inflammatory cytokines, the most important being interleukin 6, while ESR reflects the whole acute phase process, mostly as a response to fibrinogen production.[2,13] The level of CRP rises proportionally to the intensity of the inflammation process, being sensitive to subtle changes in the acute phase response.[1,13,14] CRP is a preferred serologic marker of acute inflammatory conditions because of its faster kinetics and shorter half-life (19 hours) that result in a quick fall once inflammation resolves, thus being helpful for not only diagnosis but also response to treatment.[2,4] However, many other conditions that cause tissue damage, such as malignancies, trauma, burns, surgery, and others, are associated with the rise of CRP.[15]

Although continuous efforts have been made in terms of research and discovery of new inflammatory biomarkers with higher diagnostic sensitivity and specificity, ESR and CRP are still the most widespread laboratory tests used in the initial screening of inflammatory-associated conditions. This can be explained in part by the fact that these tests are low cost, easy to perform, and available in barely all laboratories worldwide. While CRP obviously retains its prominent position in laboratory diagnostics of inflammatory conditions, speculations have been raised about the disappearance of ESR from clinical practice due to its lack of specificity. And yet, although it seems like ESR will be completely marginalized, new automated techniques for ESR measurement have been introduced in clinical laboratories, paving the way to the revival of ESR.[16,17] Nowadays, most laboratories have transitioned to the use of automated methods for ESR determination instead of the original manual Westergren technique, making ESR measurement faster, easier, and therefore still attractive.[16] In fact, ESR is always included in the list of top 25 tests by volume at different referral hospitals from five different countries.[18] Along with its established position in the diagnostic criteria of selected clinical conditions, it is more than evident that ESR will not soon completely disappear from clinical practice.

This interesting course of events encouraged us to reexamine the diagnostic accuracy of ESR and CRP through a systematic review of the literature and meta-analysis of published studies that have assessed the diagnostic performance of ESR and CRP in various inflammatory conditions. This study had the aim to compare published data regarding diagnostic sensitivity and specificity of ESR and CRP in the diagnosis of acute location-confined or systemic inflammation, of mild or moderate degree, to get a profound insight into their utilization but also diagnostic utility of their use.

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