Elevated ANA normal sed rate
by Nathan Wei, MD, FACP, FACR
Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.
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Before we talk about the significance of an elevated ANA and a normal sed rate, let’s discuss what these mean...
Antinuclear antibodies (ANAs) react with a variety of nucleoproteins (proteins found in the nucleus of cells). In ANA testing, patient serum is allowed to react with a tissue substrate fixed on a slide. Most laboratories employ a HEp-2 cell line (a line of human epithelial cells) as the substrate for this test. The sensitivity of ANA tests can differ when other animal-based substrates are used.
Antibodies bound to the nuclei of the substrate are then detected by a second antibody labeled with a fluorescent tag. The results are expressed as the highest titer at which fluorescence is detected. Although titers of 1:20 or 1:40 are commonly reported as positive, titers of 1:320 or higher are usually considered more clinically meaningful.
ANA tests are used most often for diagnosis of SLE. In an unselected population, the sensitivity is 98% and specificity 90%. Almost all patients with SLE have positive ANA test results; false-negative results are rare. About 40% of patients with rheumatoid arthritis will have a positive ANA, as will 70% of patients with Sjögren's syndrome, 90% of patients with scleroderma, 25% of patients with polymyositis, and 10% to 20% of patients with systemic vasculitis.
False-positive results occur in some healthy individuals and in some patients with a family history of SLE. Up to 5% of healthy elderly persons will have a positive result, and high-titer results are more likely to be associated with an underlying illness than low-titer results.
In an unselected population, the positive predictive value of ANA testing for detection of SLE is 30% to 40%, while the negative predictive value is greater than 99%. Therefore, about two thirds of patients with positive ANA test results will not have SLE, and only rarely will a person with a negative result have SLE.
The ANA test should be ordered when multi-systemic illness suggests SLE. It may also be useful in evaluating patients with photosensitive skin rashes, joint inflammation, kidney inflammation, or low blood cell counts not explained by other causes. This test is not useful for evaluating the course of SLE or other rheumatic diseases. Titers do not accurately reflect changes in disease activity and are not responsive to fluctuations in clinical status.
ANA tests can be false-positive in many conditions, including rheumatoid arthritis, subacute bacterial endocarditis, human immunodeficiency virus infection, liver disease, malignancy, type 1 diabetes, pulmonary fibrosis and multiple sclerosis. False-positive tests also occur in patients with silicone gel implants, pregnant women and the elderly.
Despite high sensitivity, a negative ANA test does not rule out systemic lupus erythematosus. Rarely, patients with isolated anti-Ro (anti-SS-A) antibodies or anti-single-stranded DNA (anti-ssDNA) have a negative ANA test. Also, patients with the systemic lupus erythematosus-like antiphospholipid syndrome may be ANA negative. Conversely, ANA results are positive in 5 percent of tested women and older patients.
The erythrocyte sedimentation rate (ESR) is a measurement of the height of the layer of red blood cells that settle in a tube of anti-coagulated blood in a specific unit of time, most commonly one hour. The upper limit of normal for persons 50 years of age and younger is 15 mm per hour in men and 20 mm per hour in women. Over the age of 50, the upper limit of normal for the ESR is 20 mm per hour in men and
30 mm per hour in women.
The ESR is a diagnostic criterion in polymyalgia rheumatica and temporal arteritis. An elevated ESR value has a sensitivity of approximately 80 percent for polymyalgia rheumatica and greater than 95 percent for temporal arteritis.
The ESR is a means for staging rheumatoid arthritis, rather than a major diagnostic criterion. The ESR value tends to correlate with clinical disease activity and to parallel such symptoms as morning stiffness and fatigue, although joint examination is far more useful in assessing synovitis. The sensitivity of an elevated ESR value is approximately 50 percent in patients with signs of rheumatoid arthritis. However, the specificity of an elevated ESR is quite low, limiting its use as a diagnostic test.
The ESR is often normal in SLE even in the face of active disease. Therefore, use of the ESR to monitor disease activity with the ESR alone is not advised. Markedly elevated ESRs in patients with SLE may signify the presence of infection.
In our clinic we do not pursue ANAs unless they are greater than 1:160, or if a patient has other symptoms that warrant it. A positive ANA by itself is meaningless.
By the same token a normal sed rate is meaningless in a patient with known SLE if they are having symptoms of a flare.
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