The diagnosis of rheumatologic diseases is based on clinical information, blood and imaging tests, and in some cases on histology. Blood tests are useful in confirming clinically suspected diagnosis and monitoring the disease activity. The tests should be used as adjuncts to a comprehensive history and physical examination.
The value of a test in diagnosing a certain condition depends on its pretest probability. A positive test result with high pretest probability helps to make a diagnosis, but a negative test result with low pretest probability helps to rule out the diagnosis. However, clinicians cannot rely heavily on blood tests in making the diagnosis of rheumatologic diseases, except for certain tests that are highly specific for certain diseases. Improper application of these tests leads to misdiagnosis, inappropriate therapy, and unnecessary health care expenses. This chapter discusses blood tests that are useful in evaluating various rheumatologic diseases.
Acute-phase reactants
Acute-phase reactants are proteins whose plasma concentration increases (positive acute-phase proteins) or decreases (negative acute-phase proteins) by at least 25% during inflammatory states.1 Box 1 lists positive and negative acute-phase reactants. The effect of inflammatory molecules such as interleukin (IL)-6, IL-1, tumor necrosis factor α (TNF-α), interferon gamma (IFN-γ), and transforming growth factor β (TGF-β) causes a change in hepatic protein synthesis collectively known as acute-phase response. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are the most widely measured acute-phase reactants in clinical practice.
ESR is a measure of the height of erythrocytes that fall through plasma in a Westergen or a Wintrobe tube over a period of 1 hour. ESR can be greatly influenced by the shape and number of red blood cells as well as other plasma constituents like fibrinogen, globulins, and albumins. It can be spuriously high in the absence of inflammation, as in anemia, nephritic syndrome, and hypergammaglobulinemia, and it can be spuriously normal in cryoglobulinemia and hemoglobinopathy. ESR increases steadily with age, and the upper limit varies with sex; hence, ESR is difficult to interpret compared to CRP.
The concentration of CRP in serum is more sensitive than ESR to evaluate and monitor inflammation, and it is independent of factors that affect ESR. It correlates better with disease activity, and the rise in CPR level is seen much earlier than that of other acute-phase reactants, usually 4 to 6 hours after tissue injury.
Box 1: Positive and Negative Acute-Phase Reactants
Positive Acute-Phase Reactants
Alpha1-antitrypsin
Ceruloplasmin
Complement components
C-reactive protein
Ferritin
Fibrinogen
Haptoglobin
Serum amyloid A
Negative Acute-Phase Reactants
Albumin
Transferrin
Transthyretin
Both ESR and CRP levels can be elevated in a wide variety of conditions including trauma, infection, infarction, neoplasms, and inflammatory arthritis. Usually ESR and CRP levels correlate well, but in some patients levels may be discordant for reasons that are unclear. They are very useful in monitoring disease activity in rheumatologic conditions such as rheumatoid arthritis, polymyalgia rheumatica,2 and giant cell arteritis. Some studies have shown that the pretreatment ESR value is of some prognostic value in polymyalgia rheumatica. Most patients with active lupus have normal or minimally elevated CRP levels, and markedly elevated concentrations of CRP in SLE should raise a suspicion of bacterial infection. Other causes for elevated CRP in SLE patients include serositis, synovitis, and vasculitis.