Learn about the challenges of Lyme disease testing, including false positive results and the limitations of current diagnostic methods. Understand why Lyme disease should be a clinical diagnosis and the importance of considering clinical signs and symptoms. Find out how other diseases and conditions can cause a false positive Lyme test and the need for improved diagnostic tests.
Lyme disease, caused by the bacterium Borrelia burgdorferi transmitted via a black-legged tick bite, is the fastest-growing vector-borne infectious disease in the United States. More than half a million people are diagnosed and treated for Lyme disease each year. And that’s just the number of reported cases; many more go undiagnosed, because Lyme is difficult to detect. If someone is lucky to get a tell-tale erythema migrans rash (often, but not always, shaped like a bullseye), then it is easy to spot Lyme. If not, faulty serologic testing and nonspecific symptoms that mirror other illnesses can make it difficult to catch Lyme disease early when it is easiest to treat. Blood tests for Lyme disease can give either a false negative result or a false positive result. Let’s walk through the trouble with current Lyme disease testing and talk about how Lyme disease should be diagnosed.
Lyme Disease Diagnostic Testing
The CDC currently recommends a two-tiered laboratory test for Lyme disease. You’ll have a blood sample drawn at a lab such as Quest diagnostics. The first screening test done is called an ELISA, or enzyme-linked immunoassay, which looks for antibodies for Lyme disease in your blood. If that test comes back positive, you will then have a second test, either a Western Blot test or sometimes another type of ELISA test. Per CDC guidelines, for a Lyme test to be considered positive, both tiers of tests need to yield a positive result.
With some illnesses, a blood test can definitively confirm or rule out whether you have a disease. Unfortunately, that is not true for Lyme disease, because there are several limitations to testing. First, because tests only look for antibodies against Lyme, not for the bacteria itself (the way a PCR or polymerase chain reaction test would), your immune system must build up enough antibodies to be detected on a test. It can take a while for this to happen, so serological testing is less sensitive for early Lyme.
If initial testing gives a false negative result and you do not get a correct diagnosis when you have early localized symptoms, the infection can spread to other parts of the body, causing serious manifestations like Lyme arthritis, Lyme carditis, and neurological Lyme disease. The sensitivity of testing improves for early disseminated and late disseminated Lyme disease, but by then, treatment becomes more difficult, and you could develop chronic Lyme disease.
Another limitation of Lyme disease testing is the way the Western blot test is interpreted. The Western blot test looks for bands of IgG (Immunoglobulin G) and IgM (Immunoglobulin M) antibodies for Lyme. Per the CDC, you need to have two of three positive IgM bands or five of 10 positive IgG bands in order for your test to be considered positive. This is very strict criteria that was only ever meant to be used for surveillance, not diagnostic purposes, but many doctors still use it. Therefore, if you have a few positive bands but not enough to meet the stringent CDC criteria, your test will be considered negative even though you do have antibodies for Lyme.
Moreover, it’s impossible to tell if the antibodies that do show up are from an old or a new infection, because antibodies can persist for years.
Because it’s so hard to get accurate results from current tests, Lyme should be a clinical diagnosis. This means that your healthcare provider should do a physical examination and evaluate you for clinical signs of Lyme disease symptoms, such as fever, fatigue, aches, and swollen lymph nodes in early Lyme and headache, joint pain, Lyme carditis, facial paralysis, neuropathy, sleep disturbances, and brain fog in later stages of the disease. Blood tests can help confirm a clinical diagnosis but, because of their inaccuracy, they shouldn’t be used alone to diagnose or rule out Lyme. Other more invasive procedures like testing the cerebrospinal fluid or synovial fluid are sometimes used to help diagnose Lyme. Once a healthcare provider has diagnosed you with Lyme, they will start you on antibiotic therapy.
Lyme Disease Diagnosis Criteria
When looking at clinical findings that might point to Lyme disease, your health care provider should consider if you have signs and symptoms of Lyme disease, whether you have spent time in an endemic area and therefore have a likely exposure to infected black-legged ticks, and the results of laboratory tests when indicated. For more information on Lyme disease diagnosis, click here.
Statistics of False Positive Lyme Tests
One limitation of blood tests for Lyme is that they can actually give a false positive result. Depending on the lab used and the sensitivity of the test, as many as 57% of positive Lyme tests could be false.
Factors That Can Cause a False Positive Lyme Result
There are a few reasons that Lyme tests could come back as false positive. Infection with other diseases, including other tick-borne diseases or some viral, bacterial, or autoimmune diseases, can cause cross-reactivity that can result in a false positive Lyme test. Since current Lyme tests cannot distinction between old and new infection, or tell if an infection has been cured, a current positive test might not be accurate. If you were previously vaccinated for Lyme when the Lymerix vaccine was available, you have antibodies in your blood that could cause a false positive test result. There is also the possibility of laboratory errors, and there are technical considerations like how different labs and doctors interpret tests (such as which Western blot bands indicate a positive or negative test).
Conditions That May Lead to a False Positive Lyme Test
Infection with other illnesses such as other tick-borne illnesses (co-infections), autoimmune disorders and rheumatologic conditions, conditions like lupus, HIV, syphilis and Epstein-Barr virus, and viral and bacterial infections with similar symptoms can lead you to have a false positive Lyme disease test.
Challenges of Lyme Disease Testing
There are many challenges to current Lyme disease testing including variability in test performance, and sensitivity and differences in diagnostic criteria and guidelines. Though Lyme disease is a clinical diagnosis that should only be corroborated, not confirmed, by laboratory tests, many patients experience challenges in receiving an accurate diagnosis. GLA seeks to transform the tick-borne disease diagnostics space by supporting innovative strategies that will better detect Lyme and other tick-borne diseases, preventing suffering from missed or delayed diagnosis. GLA recognizes the critical need for developing new and improved diagnostic tests. Learn more about the research we support.
***
