January 12, 2018

Your Lyme Disease Test Results Are Negative, but Your Symptoms Say Otherwise

What happens when everything adds up to a likely diagnosis of Lyme disease except the lab test results? It’s a question doctors face more often than many people realize.

Even if a patient has potentially been exposed to ticks and demonstrates symptoms that could be caused by Lyme disease, many doctors will still rely on laboratory tests to definitively determine whether a patient does or does not have the disease. And that can have serious, even deadly consequences for patients that have Lyme disease yet don’t start treatment because of a negative lab test result(s).

So why would an infected patient test negative for Lyme disease? It turns out there are a number of reasons that could trigger false negative test results. The following article highlights some of the issues that may be at fault. Be sure to share these potential concerns and considerations with your doctor when discussing diagnostic testing options for Lyme disease.

The Test Isn’t Designed to Detect the Exact Disease-Causing Bacteria You Have

A number of Lyme disease lab tests are designed to identify only a few species of the Borrelia bacteria that can cause Lyme disease. In the United States, for example, many tests are only designed to detect B. burgdorferi, leaving out many other species that are less common yet still known to cause the disease in humans, including the recently discovered B. mayonii. This inability of many lab tests to cast a wide enough net of detection could result in false negative results for patients infected with different strains of disease-causing Borrelia.1https://www.lymedisease.org/lyme-sci-testing/

Inaccurate Results Due to Lower Test Sensitivity

Many doctors and labs adhere diligently to the two-step tests – for Lyme disease that are approved by the FDA and recommended by the CDC, which involves an initial enzyme-linked immunosorbent assay (ELISA) followed by a Western blot test. Both tests are designed to detect antibodies in the patient’s blood to the B. burgdorferi bacteria and, according the CDC, both must be positive for a patient to be diagnosed with Lyme disease. However, recent studies have raised concerns about the accuracy of these tests, particularly the ELISA, which has been found to have a poor sensitivity rate, or ability to detect antibodies in the blood. Recent studies, in fact, report that the ELISA and Western blot can miss up to 60 percent of well-defined Lyme disease cases.2Molins CR, Ashton LV, Wormser GP, Hess AM, Delorey MJ, Mahapatra S, Schriefer ME, Belisle JT. Development of a Metabolic Biosignature for Detection of Early Lyme Disease. Clin Infect Dis. 2015 Mar 11. http://danielcameronmd.com/relying-on-a-negative-lyme-disease-test-can-prove-deadly/

Indirect Versus Direct Testing

Both tests used in the CDC recommended two-step process are indirect methods of diagnosis—meaning they do not detect the actual Lyme disease bacteria itself but, instead, measure the body’s immune-system response to the presence of disease-causing bacteria. However, a number of factors can prevent the body from producing antibodies, including the following:

  • Timing: If conducted in the early stages of Lyme disease, a patient’s body may not have developed a sufficient enough number of antibodies to detect. This issue can be compounded by the lack of sensitivity of the ELISA test.
  • Immunity Suppression: The saliva of infected ticks contains specific immune-suppressing components that can delay or prevent the activation of a person’s immune response. These components are designed to prevent the body from effectively “fighting off” the Lyme disease–causing bacteria so it has a chance to take hold.
  • Antibiotics: If patients are taking antibiotics at the time of the Lyme disease test, they may not produce enough antibodies to be detected by the test.
  • Modified Form of Borrelia: In some patients, the Borrelia bacteria will transform into a cyst, which will prevent the body’s immune system from producing antibodies.
  • Weakened Immune System: False negatives can also result in patients in whom the immune system is weakened or compromised due to coinfection with another illness.
  • Seronegative patients: These patients do not produce antibodies

Direct testing methods can eliminate some of these variables because they don’t rely on the body’s response to a pathogen but rather look for the presence of the disease-causing bacteria directly. Polymerase chain reaction (PCR) assays, for example, are used to identify Lyme bacteria in the patient’s blood or urine.3http://www.tiredoflyme.com/4-reasons-a-lyme-test-will-come-back-negative-even-if-a-person-truly-has-lyme-disease.html




Different Labs, Different Results

When it comes to testing for Lyme disease, the quality of the lab conducting the test can also affect the reliability of the results. That’s because different labs use different protocols and techniques to perform each test. Those with more advanced procedures and capabilities provide higher levels of accuracy and precision across various types of tests. By improving diagnostic precision, clinicians are not only able to more accurately detect Lyme infection but, in some cases, the specific stage of a patient’s Lyme disease infection.4http://www.tiredoflyme.com/4-reasons-a-lyme-test-will-come-back-negative-even-if-a-person-truly-has-lyme-disease.html

Co-Infection Complexities

including Tick-Borne Relapsing Fever (TBRF), Powassan, Babesiosis, Ehrlichiosis, Anaplasmosis, and Rickettsiosis. In some cases, patients will test negative for Lyme disease because they have a co-infection with one or more of these other illnesses. In other cases, they may not have Lyme disease but one of these other illnesses instead. Depending on a patient’s symptoms, doctors should consider the potential of a coinfection as a factor when all symptoms point to Lyme disease but test results are negative.

For patients and doctors, being aware of the many factors that can influence Lyme disease lab tests can better inform your perspective and reliance on the results. Doctors should consider multiple types of tests, a panel approach, to increase the chances of detecting the disease. Additionally, they should always consider the patient’s lab test results in conjunction with their current or previously reported symptoms, as well as risk factors that heighten their probability of exposure to ticks or regions where Lyme disease and other tick-borne diseases are prevalent.

Additional Resources

References   [ + ]

1. https://www.lymedisease.org/lyme-sci-testing/
2. Molins CR, Ashton LV, Wormser GP, Hess AM, Delorey MJ, Mahapatra S, Schriefer ME, Belisle JT. Development of a Metabolic Biosignature for Detection of Early Lyme Disease. Clin Infect Dis. 2015 Mar 11. http://danielcameronmd.com/relying-on-a-negative-lyme-disease-test-can-prove-deadly/
3, 4. http://www.tiredoflyme.com/4-reasons-a-lyme-test-will-come-back-negative-even-if-a-person-truly-has-lyme-disease.html