Lyme Disease

Serology, or blood work, is currently the only type of diagnostic test for Lyme disease approved by the US Food and Drug Administration.

Serologic tests are designed to detect antibodies that the immune system makes in response to an infectious organism, in this case the spirochete Borrelia burgdorferi. Before testing a patient for Lyme disease, it is important to consider the likelihood that you are infected. Factors to consider are:

  • Symptoms: Do you have signs and symptoms consistent with the disease?
  • Geography: Has you been in an area where the disease occurs?
  • Behaviors: Do you have risk factors for exposure to ticks?

If you decide there is a reasonable chance that you have Lyme disease, serologic testing may be helpful. Remember, however, that it can take several weeks after infection for a serologic test to become positive. This means that patients with early stages of Lyme disease, such as erythema migrans, may have a negative serologic test when first tested. For this reason, it is recommended that such patients be diagnosed and treated immediately, without serologic testing. In contrast, patients who have been ill for 4 weeks or longer will almost always have antibodies, if infected. Consequently, serologic testing is very useful for diagnosing patients with later stages of disease, such as Lyme arthritis.

When testing for antibodies for Lyme disease, CDC recommends a 2-step testing process. In the first step, serum is tested using a highly sensitive but inadequately specific quantitative assay, most commonly an enzyme immunoassay, such as an ELISA. If this first test is negative, no further testing is indicated. If the first test is positive or indeterminate (also called “equivocal” or “borderline”), a second-step test should be performed.

In the second step, serum is tested by immunoblotting, either with Western or striped blots, to identify IgM and IgG antibodies against several different B. burgdorferi antigens. Some of these antigens are recognized by antibodies to other common organisms, so even uninfected patients will usually have at least 1 reactive band. The important issue is the number of bands. To be considered positive, the serum should react with at least 5 of 10 scored bands on the IgG assay and with 2 of 3 scored bands on the IgM assay.

Two important caveats:

  • Do not skip steps in the 2-step process. Skipping steps, for example performing a Western blot alone, increases the chances of a false-positive result. The higher false-positive rate has ranged from 1.5%-8%, depending on the population studied.
  • A positive IgM immunoblot is only meaningful during the first 4-6 weeks of illness. After that time, an infected patient should have a positive IgG immunoblot as well. If they don’t, it strongly suggests that the IgM result is a false positive.

Unfortunately, there is a lot of misinformation about Lyme disease testing, most notably that the first-step tests are insensitive. This myth is based on tests that are no longer in use and inappropriately expecting positive results for patients who are in the early stages of infection, for whom serologic testing is not recommended. In truth, first-tier tests for Lyme disease are quite sensitive — sensitive enough to react in some patients with other spirochetal diseases, such as tick-borne relapsing fever, syphilis, or leptospirosis, as well as with other infectious and noninfectious conditions.

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