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...

From the American College of Rheumatology

Antinuclear antibodies (ANAs) are antibodies that react with a variety of proteins found in the nucleus of cells. In ANA testing, patient serum is placed on a tissue substrate fixed on a slide. Most laboratories use a HEp-2 cell line (a line of human skin cells) as the substrate for this test. The sensitivity of ANA tests can differ when other animal-based substrates are used.

Antibodies that bind to the nuclei of the substrate are detected by a second antibody labeled with a fluorescent tag. The results are given 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 considered significant.

ANA tests are used most often for diagnosis of systemic lupus erythematosus (SLE). The sensitivity is 98% and specificity 90%.

Almost all patients with SLE have positive ANA test results; false-negative results are rare. Studies have shown the following: about 40% of patients with rheumatoid arthritis will have a positive ANA; 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 people and in some people 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 medical problem than low-titer results.

The positive predictive value of ANA testing for detection of SLE is 30% to 40%, while the negative predictive value is greater than 99%. This helps with diagnosis since 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 SLE is suspected. Levels often don't accurately reflect changes in disease activity and don't change with clinical status.

ANA tests can give a false-positive result 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 antiphospholipid antibody syndrome may be ANA negative. On the other hand, ANA results are positive in 5 percent of tested women and older patients.

The erythrocyte sedimentation rate (ESR) is a measurement of the speed a layer of red blood cells settle in a tube of anti-coagulated blood in a specific measure of time, usually 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 test used for 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 estimating disease activity in rheumatoid arthritis. The ESR value tends to correlate with clinical disease activity and to parallel symptoms such as morning stiffness and fatigue, although joint examination is also useful in assessing joint inflammation. 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 in SLE is not advised. Markedly elevated ESRs in patients with SLE may signify the presence of infection.

Note: 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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