Let’s Talk About Testing for Lyme Disease, Part 2 – Blood Tests

If you went for a hike and found a tick on your body, you should assume the worst (you got infected) and hope for the best (you dodged a bullet). But while you will be smart and assume the worst, local lab testing is still acting as if this is merely a pesky little problem and one little blood test will identify everything you need to know. (As if!) So, these labs usually only check for one strain of Borrelia—even though there are multiple strains causing disease. Similarly, if your doctor were to check for Babesia or Bartonella--common infections we see in our patients--the same problem exists. There are multiple strains, and one test will not necessarily pick up all the potential species, not to mention that other tick-borne infections like Ehrlichia, Anaplasma, rickettsial species, tularemia and/or viruses can be transmitted with a single tick bite. That’s one reason why you can be sick and stay sick and no one will believe you.

Lyme testing can be unreliable, as can testing for certain other tick-borne diseases, and a broad screening approach is needed. Let’s focus today on Lyme disease. Future Substacks will address other tick-borne infections.

Simple Blood Tests Aren’t Enough

Currently, the CDC recommends a 2-tiered approach for blood tests, with an ELISA test followed by a Western blot test for the diagnosis of Lyme disease. These tests have been designed to screen large numbers of individuals from a public health perspective and should not be used as the sole method of diagnosis. Even the CDC says this on their website, highlighting that Lyme disease is a “clinical diagnosis” and that blood tests should be used to confirm a clinical diagnosis.

Although there are several different laboratory tests to diagnose Lyme disease (an ELISA test, C6 ELISA, Western Blot, IFA, Immunoblots, Elispot, Spirotest, PCR/DNA test, or occasionally a phage test, Nanotrap test and/or culture), these tests each have their pros and cons, and can miss establishing the diagnosis because they are not sensitive enough to always pick up the presence of the bacteria.

As a result, you will see all sorts of claims of accuracy of Lyme testing by different doctors and websites, but the key point is this: A standard ELISA test followed by a Western blot test from a local laboratory will miss approximately half of those infected with Lyme disease, as they are notoriously inaccurate—which is why you need to use a really good specialty lab, as they will test for more than one strain of Borrelia species. Ask your healthcare provider to run a Immunoblot blood test through a reliable laboratory. I recommend igenex.com lab in California, as my first line test, as they use several of the most common strains causing disease to improve their testing. And we have clinically validated their findings for more than 2 decades.

The Western blot test and Immunoblot has 5 bands (proteins) that are specific for Lyme exposure; these are the 23, 31, 34, 39 and 83/93 kDa bands. The 58 kDa band is also a band frequently seen in Lyme disease, and if other diseases have been ruled out, any one of these bands on an Immunoblot with the right symptoms means you likely have been exposed to Lyme. The more bands you have, the higher the probability of exposure, but to be clear: if you have a multisystemic illness with migratory pain and have ruled out other diseases, even one specific Lyme band on an Immunoblot with a high score on the HMQ tells me you have been exposed to a Borrelia species. And some of the sickest patients don’t make antibodies, which is why standard two-tiered testing can also be negative.

Clinical Note: If you have the 31 band on a Western blot, it could mean exposure to Lyme, but also this band can cross react with the Epstein Barr virus (EBV) and autoimmune diseases. That is why I prefer the Immunoblot, since the 31 kDa band is more specific without false positives.

One of the reasons testing is such a mess is that the bacteria causing Lyme disease (and associated infections like Bartonella) can hide in your cells and under biofilms so your immune system can’t recognize them. Lyme organisms can also keep changing their outer surface proteins, like relapsing fever Borrelia do, to fool your immune system into not recognizing them. This helps to explain why it can persist, while at the same time suppressing immune function in some people. In that scenario, you don’t make antibodies in the first place, so you can’t identify the pathogen or properly destroy it.

When you do get a diagnosis of Lyme and/or Bartonella, it’s really, really important to check how well your immune system is functioning. You need all the tools in your body’s arsenal to fight the bacteria. The problem is that the clinical diagnosis overlaps symptoms of many other diseases, including many tick-borne co-infections. This can leave you and your doctor confused as to why you are sick.

That’s when you can fall into the Lyme rabbit hole of misdiagnosis and inappropriate treatment.

Assuming that so many ticks are now co-infected, if you test positive for one tick-borne disease, it’s more than likely that you have another one. One clue is that you are extremely sick--co-infections increase most underlying symptoms of Lyme disease. (You already read about symptoms in previous Substacks.)

The rule in my patients is that co-infections are the rule, not the exception!

False Negative Results

False negatives or false positives have led to countless misdiagnoses and improper treatment—and in my experience, false negative testing is by far the biggest problem. Especially when you consider that roughly 1 out of 7 people on this planet have now been exposed to Lyme disease, according to BMJ Global Health.

False negative testing often happens to people who suddenly notice a bullseye rash or a spreading rash that is consistent with exposure to a Borrelia species and immediately get tested. They are likely to have a false negative result because the body hasn’t yet had the time needed to develop antibodies. This can also happen if you start taking antibiotics right away. And once your blood tests are positive for antibodies, you might continue to have positive results for months or even years, even if you are no longer infected--which can be quite confusing and frustrating.

[Image by David Garrison from Pexels.com]

When Blood Tests Aren’t Enough

So the bad news is that standard blood tests can be inaccurate and not be able to pick up the broad range of species associated with Lyme, Babesia and Bartonella. The good news is that you have other options, and I want you to share them with your doctor so you get the tests you need.

*Standard blood tests like a complete blood count (CBC) and comprehensive metabolic profile (CMP) will be useful in the acute stages of certain co-infections. A low white cell count, and/or low platelet count, and/or elevated liver functions (1, 2, or all 3 of these abnormalities) can be seen in acute phase of tick-borne co-infections with Ehrlichia, Anaplasma, Rocky Mountain Spotted Fever, Q-fever, Typhus, hard-tick relapsing fever, Borrelia Miyamotoi Disease, (BMD), Babesia, Heartland, and the Bourbon virus.

--If you have any of these abnormalities on standard blood tests like a CBC and CMP early in the course of your illness, with symptoms consistent with an acute tick-borne diseases (high fevers, severe headaches with new neuropsychiatric symptoms, significant muscle aches and joint aches, severe fatigue, chest pain and shortness of breath, new GI symptoms including nausea, vomiting and/or diarrhea) all of these infections (except Babesia and viruses) can be effectively treated with doxycycline--and should be, as they can be fatal in some cases if you wait for antibody testing to return. So even though simple blood tests aren’t enough, getting a CBC and CMP result early in your illness at least gives the Medical Detective clues that you have been exposed and helps inform treatment that may prevent long term complications.

*If you suspect exposure to tick-borne co-infections, I recommend a combination of antibody titers, PCR, and FISH (RNA) testing for the most common co-infections, especially Babesia (antibody testing for B. microti, B. duncani, and on occasion, B. odocoilei) and Bartonella species (Bartonella henselae, B. quintana, B. bacciliformis, B vinsonii subspecies, B. elizabethae, Bartonella koehlerae). In many cases, the FISH test (RNA) will be positive for Babesia and Bartonella when antibody and PCR testing are negative, so it’s important to perform a panel approach of different tests to prove exposure. Both IgeneX laboratory and T labs are reliable laboratories that do FISH testing. I’ll discuss the different species of Babesia and Bartonella and how to test for them, with an emphasis on the newest and most effective treatments in future Substacks.

*There are also indirect tests that can be positive for some of these co-infections, if the above tests are negative. One of the most common ones are lymphocyte transformation tests (LTTs), which rely on your memory T cells to prove you had prior exposure to one of these pathogens.

More Clinical Advice for Confirming a Lyme Diagnosis

The specifics here should help your doctor order the correct tests for you.

I use a panel approach, as mentioned earlier. If I clinically suspect Lyme disease, because of a high Questionnaire score and specific symptoms (like migratory joint pain, migratory muscle pain and/or migratory nerve pain), there are indirect tests (measuring antibody production) and direct tests like those measuring DNA (PCR) or RNA (FISH) as well as antigens in the urine (Nanotrap test for the 31 kdA protein) or phage testing that can be used to confirm the clinical diagnosis.

Indirect testing that can be done on a panel approach (i.e., doing several tests one after the other, if one is negative) includes checking for Immunofluorescent Antibodies (IFA), an ELISA, C6 ELISA (which checks for 3 strains of Borrelia, not one, but also cross reacts with hard tick relapsing fever Borrelia, Borrelia miyamotoi), Lymphocyte transformation testing (LTT, ElispoT), and checking for immune activation (iSpot, Spirotest). You might find that one or two of these tests is negative in a panel approach, but the others can be positive, confirming your clinical suspicion of prior exposure.

I usually start with an ELISA from a local lab, but also do an IgeneX Lyme Immunoblot as first-line testing. In general, the IgeneX Immunoblot alone will be adequate in most cases to provide evidence that you have been exposed to a Borrelia species without a full panel approach. If you do both an IgM and IgG Lyme Immunoblot (remembering that a positive IgM Immunoblot is seen in both early and late disease, and is not a false positive), it is common for an Immunoblot to show evidence of at least one Borrelia specific band after exposure. This is where we play the game Lyme Bingo. Any one of the following bands, whether weakly positive or positive, proves exposure to a Borrelia species: the 23 kda (Outer Surface Protein, i.e., OspC), 31 kdA (Osp A), 34 kdA, 39 kdA (highly specific), and 83/93 kdA band. The 58kdA also has recently been shown to be positive in many cases of those with a chronic Lyme infection.

However, to prove an active infection, polymerase chain reactions (PCR) which looks for pieces of DNA of the organism, or RNA testing, called Fluorescent In Situ Hybridization (FISH), can be very useful. PCR testing is a good diagnostic tool you can use from a local laboratory, especially for those who continue to have symptoms but have negative blood tests, but it will only pick up the infection roughly 10% of the time. You’ll likely need multiple samples over time, and from different sources (blood, urine, tissue, spinal fluid, etc.), and these samples should be sent to a reputable specialty lab. Although there are doctors who claim that a positive PCR for Lyme disease can be found in the blood with ‘dead DNA’, debating whether there is in fact an active infection, most scientists do not share that view, as any abnormal DNA is usually cleared from our system within 48 hours. And to be clear, in other diseases, such as hepatitis, a positive PCR for hepatitis B or C in the blood is indicative of an active infection requiring treatment. Double standards are therefore not allowed here!

One lab that does a highly sensitive PCR, called a nested PCR, is Dr SH Lee’s lab in Connecticut. The advantage of this PCR test is that there are no inhibitors in the serum interfering with the results (although contamination is still potentially a problem with any lab doing PCR testing, which is why labs like Dr Lee’s enact such strict standards of care).

I find that many of my patients who are PCR negative are positive by FISH for Lyme, Babesia, and/or Bartonella when other tests are negative, because these tests can pick up miniscule amounts of genetic material, and don’t rely on antibody production. When I do my initial and follow-up screening for Babesia and Bartonella, I like to get a FISH test from the very beginning from IgeneX (and secondly from T Labs if negative), because when it is positive, it tells you that is it likely that this organism is going to be a major factor in driving chronic illness.

Remember, some people suffering from chronic Lyme disease and Bartonella do not make adequate antibodies, as their immune system has been adversely affected. They become immune deficient. In this case, FISH testing can be very helpful, as it can detect multiple species of the organism. Also, in patients who are immunodeficient on IVIG (IV Immunoglobulins), or SQIG (subcutaneous immunoglobulins) antibodies for tick-borne testing can be falsely positive because individuals are receiving pooled serum from the general population who have been exposed. A positive FISH test avoids that problem, since it indicates an active infection.

Other direct testing which can be helpful in establishing a clinical diagnosis includes the Nanotrap test (finding the 31 band, Osp A in the urine), phage testing (through Red Labs in Belgium), and culture testing. This has been a controversial method in the past due to issues with accuracy, but IgeneX has recently unveiled a new version.

The key to understand all of the lab testing for Lyme disease is that it’s used to confirm a clinical diagnosis, not the primary way we establish the diagnosis. Taking the Horowitz MSIDS Questionnaire (HMQ) and scoring it, reviewing questions 1 +22 for Babesia exposure, and seeing if you have migratory pain, ALONG with looking at the constellation of symptoms and doing a differential diagnosis, ruling out other diseases…then doing the above tests (especially looking for Borrelia specific bands on an IgM and/or IgG Lyme Immunoblot as a first line test) while checking for physical/dermatological signs of the disease, will allow you to confirm with a high level of clinical accuracy the diagnosis of chronic Lyme disease.