ATLANTA – Correcting for age can increase the diagnostic accuracy of some lab tests used to make the diagnosis of rheumatoid arthritis or other rheumatic disorders, according to Dr. Mark Wener and Dr. Robert Lightfoot.
Dr. Wener, director of the immunology division and a member of the rheumatology division at the University of Washington, Seattle, shared his clinical pearls for how to maximize the value of lab tests for inflammation.
A patient’s erythrocyte sedimentation rate (ESR) can be used to assess inflammation, but results can be deceiving, he said, because they are affected by factors including fibrinogen, globulins, albumin, and hematocrit.
In cases of acute inflammation, increased fibrinogen in turn increases the ESR, just as increased immunoglobulins that are present in chronic inflammation increase the ESR, Dr. Wener said. In addition, malnutrition, multiple myeloma, and malignancy and other noninflammatory conditions can raise the ESR.
The 2010 ACR/EULAR diagnostic criteria for rheumatoid arthritis (RA) recommend that clinicians take age and gender into account when using ESR. However, most labs don’t adjust for age, Dr. Wener said. For example, the incident inflammation asso ciated with age-related gingivitis can elevate the ESR even if no other inflammation is present.
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Although most labs do not include age-adjusted reference ranges in their reports, clinicians can correct for age at the bedside by using a simple formula, said Dr. Wener. Use of a formula to determine the upper limit of the reference range for ESR can help physicians obtain an age-adjusted ESR (BMJ 1983;286:266):
• Men: Upper limit of normal ESR = age/2.
• Women: Upper limit of normal ESR = (age +10)/2.
Age and gender also play a role in the elevation of C-reactive protein levels, Dr. Wener said (J. Rheum. 2000;27:2351-9). He shared a similar formula to adjust for age and gender when considering CRP levels as an indicator of rheumatic disease.
• Men: Upper limit of normal CRP (mg/L) = age/5
• Women: Upper limit of normal CRP (mg/L) = (age + 30)/5
In general, ESR and CRP are elevated in patients with active RA, inflammatory RA, or polymyalgia rheumatica, Dr. Wener said. In contrast, patients with osteoarthritis and fibromyalgia rarely have elevated ESR and CRP levels, although age alone can increase both values, he emphasized. In addition, some patients with localized, noninflammatory disease or localized OA might have normal ESR and CRP values, and ESR and CRP levels vary in patients with chronic bursitis and in gout or other crystal diseases.
The most practical uses for ESR and CRP are for confirmation of inflammatory disease and for monitoring inflammation in cases of RA, although these tests are less reliable as measures of RA disease activity, said Dr. Wener. However, ESR and CRP have shown high sensitivity rates (92% and 100%, respectively) in identifying giant cell arteritis, he added.
Dr. Lightfoot, professor of medicine in the rheumatology division at the University of Kentucky, Lexington, added his clinical pearls for using the antinuclear antibody test (ANA) to diagnose rheumatic disease. "There are between 100 and 150 different antigens in the nucleus that can be detected in the indirect immunofluorescent ANA," said Dr. Lightfoot. "But we only know what about 10 of those antigens are."
The same ANA results might occur in both a healthy person and someone with confirmed RA, Dr. Lightfoot said. Make sure an IFA ANA is done as part of any ANA screening, especially if findings from an ANA panel show a negative ANA, or if an ANA is positive without a titer, he said.
In addition, it’s important to know the reliability of an anti-nDNA assay, because a positive anti-nDNA is often a false positive, said Dr. Lightfoot. "The biggest problem with all anti-nDNA assays is contamination of the antigen with single-stranded portions," he said. "Antibodies to single-stranded DNA are less specific than the ESR."
Dr. Wener has served as a consultant for Takeda Pharmaceuticals, and he has a contract for lab testing and imaging with Bio-Rad Laboratories. Dr. Lightfoot had no financial conflicts to disclose.