Reliability of Lab Testing for Lyme Disease

Peter L. Salgo, MD: Since you brought up diagnostic criteria, how on earth do we make the diagnosis? We mentioned a blood test. What are the guidelines in terms of how you work this up? What are you looking for? What is essential to make the diagnosis?

Samuel Shor, MD, FACP: The classic [Centers for Disease Control and Prevention] CDC and [Infectious Diseases Society of America] IDSA guidelines use something called a 2-tiered system. The 2-tiered system involves a screening test called ELISA (enzyme-linked immunosorbent assay). If that ELISA test is positive, it is followed by a confirmatory Western blot test. They’re just 2 different types of technology. One is more sensitive, the other is more specific. In the setting of HIV, whereby the ELISA test is 99.9% sensitive, the Western blot is in the order of 98% specific. In the setting of Lyme disease, it’s about 50%, in the 2-tier. The 2-tiered system, cumulatively, is about 50% sensitive across the board.

Peter L. Salgo, MD: You’re basically telling me that the blood test isn’t so good?

Samuel Shor, MD, FACP: Correct. And the statements that it’s highly sensitive in late neurologic neuroborreliosis, are, in large part, based upon a study by Dr. Allen Steere, published in 2008. In order to be included in that study, in that analysis, you had to have had 2-tier positivity.

Peter L. Salgo, MD: If I understand you correctly, 50% may not. Then, you’re left up in the air about this.

Samuel Shor, MD, FACP: Correct. You’re dealing with a number of individuals who are very ill and, in fact, there’s a component of this that we’ll talk about in more detail. There’s immune suppression that can occur, and the sicker you are—this has been published as well—the more likely this antibody immune response will not be shown. So, the sicker you are, paradoxically, the more likely you’ll be overlooked.

Peter L. Salgo, MD: That’s not unique to Lyme disease. TB does the same thing.

Leonard Sigal, MD: Let’s get back to this issue of sensitivity and specificity. The question, then, is, what’s the gold standard? Because, in order to say that a test is good or bad, you need to have a gold standard as to what the disease is.

Samuel Shor, MD, FACP: Right. Unfortunately, the gold standard is not sensitivity. The gold standard might be considered a culture.

Leonard Sigal, MD: Yes.

Samuel Shor, MD, FACP: Right, that would be the gold standard.

Leonard Sigal, MD: But, when you say 50%, what you’re saying is that, depending upon how you define Lyme disease, only 50% of those people will be positive by testing.

Samuel Shor, MD, FACP: Right, but if you’re going to use what you perceive as the gold standard of the technology that exists today, the 2-tiered system, and claim dogmatically that it is highly sensitive, when you’re skewing your population by including only those who are positive, then that is not accurate.

Leonard Sigal, MD: If you’re only including people who are positive, then the sensitivity and specificity is 100%.

Samuel Shor, MD, FACP: Right.

Leonard Sigal, MD: My only point is—and I don’t want to argue about what the gold standard is— depending upon what you consider to be the gold standard for saying that this group of patients has Lyme disease, the sensitivity and specificity of the assays, assuming they’re well done, will be different.

Peter L. Salgo, MD: Let’s do something else, if I may. Let me refocus just a bit, because the lab testing is contentious. I think your point is well taken, which is, if you say the lab testing is missing this disease, then you have to have at least some other way to define the disease other than lab testing, right?

Robert C. Bransfield, MD, DLFAPA: Correct.

Peter L. Salgo, MD: So, what else do you do to make the diagnosis?

Robert C. Bransfield, MD, DLFAPA: Well, this is similar to what happened in the 1960s in psychiatry. We had a phrase, “psychoneurosis.” Different people thought of psychoneurosis in different ways. Then, we had the DSM (Diagnostic and Statistical Manual of Mental Disorders), and the DSM helped better define various disorders.

Now, with infection, you think of PCR, culture, and antigens as proof of infection. The problem with Lyme disease, is that it’s a microbe that suppresses and evades the immune system. You cannot rely on an immune-based test for an organism that suppresses and evades the immune system.

Peter L. Salgo, MD: But we do have, certainly in medical history, plenty of experience in immune-suppressive diseases for whom lab tests work. Let’s go back to HIV, which is a classic immune-suppressive disease for which ELISA and Western blot does work.

Robert C. Bransfield, MD, DLFAPA: It’s 500 times more reliable than with Lyme disease, based on a recent journal article that was published by Michael J. Cook. Even though it does suppress, that’s a better test than what we see with the 2-tiered testing.

Peter L. Salgo, MD: How else would you make the diagnosis? First of all, let’s get some basic medicine.

Leonard Sigal, MD: Can I just return to immunosuppression a bit? If Borrelia burgdorferi were truly an immunosuppressant organism—and let’s assume for a moment it’s B-cell function, it’s antibody production—then, wouldn’t you expect to see these people with more infections?

Samuel Shor, MD, FACP: Not necessarily, it could be subtle.

Leonard Sigal, MD: They have positive blood tests for other diseases.

Samuel Shor, MD, FACP: Not to the degree of HIV, because the degree of immune suppression with HIV is far in excess. This is a subtle, indolent infectious process that’s been shown to actively suppress.

Leonard Sigal, MD: The problem with this immunosuppressant claim is that HIV is a much better immunosuppressant by destroying T cells, and yet the blood test for HIV is positive.

Peter L. Salgo, MD: I want to leave that just for a minute. We’re going to get back to it, I promise you we’ll get back to it.