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Laboratory and imaging studies rarely establish a definitive diagnosis of rheumatologic diseases in children. The prevalence of rheumatic diseases in childhood is low, and even very specific tests generate high false-positive rates unless there is a well-founded clinical suspicion for a particular illness, based upon an informed differential diagnosis guided by the history and physical exam. The utility of an assay will vary with the nature and stage of the illness. They can provide information that is useful for the evaluation and treatment.

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Markers of Inflammation

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Most rheumatologic diseases arise out of aberrant immune attack on normal cells and tissues. In many cases this immune activity is reflected in indices of systemic inflammation. Two principal markers are the erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP), but other tests also may be useful. It is important to remember that localized inflammation, such as glomerulonephritis in systemic lupus erythematosus (SLE), or synovitis in pauciarticular juvenile idiopathic arthritis (JIA), may not be reflected in these indices.

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Erythrocyte Sedimentation Rate

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The ESR measures the speed with which red blood cells precipitate out of suspension in a sample of anticoagulated blood, and is quantitated at mm/hour. In the patient with inflammation, hepatic synthesis of positively charged, acute phase reactants such as fibrinogen enables negatively charged erythrocytes to overcome electrostatic repulsion and stack together in columns (rouleaux), which fall out of suspension in the blood more swiftly. The ESR thus serves as an indirect measure of the hepatic acute phase response, in turn reflecting the presence of circulating proinflammatory cytokines such as IL-1, TNF, and especially IL-6.1 Changes in the ESR follow a time course commensurate with hepatic protein synthesis and the degradation and clearance of the relevant proteins, rising and falling gradually over the course of days.

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The advantages of the ESR are its technical simplicity and low cost, and its long track record of use. While mild elevations of ESR (<40 mm/h, for example) arise in the course of many routine illnesses, more substantial elevations warrant scrutiny for a worrisome underlying cause such as infection, malignancy, or rheumatologic disease, depending on the clinical situation.2 In rheumatologic patients who manifest an elevated ESR, this lab value may help track the response to therapy.

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Although it is a robust and useful tool, the ESR has limitations intrinsic to the assay. Processes that alter red cell properties or the plasma protein milieu may alter the ESR. ESR decreases with elevated hematocrit, aberrant red cell shape (eg, sickle cell disease and spherocytosis), and disseminated intravascular coagulation (DIC) due to consumption of circulating fibrinogen. ESR rises with anemia, pregnancy, nephrotic syndrome, and hypergammaglobulinemia, where positively charged immunoglobulins promote rouleaux formation that can markedly elevate ESR in the absence of systemic inflammation.

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C-Reactive Protein

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CRP is an innate antibacterial compound of the pentraxin class that is produced as part of the hepatic acute phase response. It was identified originally as a protein that bound the C polysaccharide of pneumococcus, but is capable of recognizing multiple other bacterial ligands as ...

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