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
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.
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.
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.
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.
CRP is an innate antibacterial compound of the pentraxin ...