Emerging Tests for Lyme Disease

Peter L. Salgo, MD: My concern as a clinician is that, when you start describing everything as a potential consequence of a particular disease, now you’ve taken away diagnostic specificity, right? If everything can be caused by it, I don’t know what to make of that.

Robert C. Bransfield, MD, DLFAPA: It can be specific patterns. There are only 3 specific symptoms: the expanding erythema-migrans rash, acrodermatitis chronica atrophicans (ACA) rashes, and ACA deterioration, which you rarely see; I’ve seen it a half-dozen times. The skin gets paper thin in the wrists and the ankles. And Hyperacusis, which is that loud noises can cause nausea, sometimes vomiting, and dizziness, you only see [this] with syphilis and Lyme disease; those are the only 3 truly specific things. Here’s the problem. Diseases that are easy to find, we’ve already figured them out. What we’re left with are the things that have multiple contributors, multiple pathophysiologic pathways, and multiple manifestations. So, 2 new patients end up with exactly the same symptoms. We have to have a different disease model for complex diseases that is different than what we’re used to having, where the disease is a simple clear thing that you can diagnose with one process. We have to think of the statistical probability of symptoms and pattern recognition. It takes a more complicated way of adding all this together.

Leonard Sigal, MD: And you’re not talking about actually making a calculation of statistical likelihood. This is all that is going on in your brain.

Robert C. Bransfield, MD, DLFAPA: Right.

Leonard Sigal, MD: Right?

Samuel Shor, MD, FACP: That’s the art of medicine.

Peter L. Salgo, MD: Are there other tests that we could do? We’ve got the ELISA test. We’ve got these other 2 tests. What else is out there that can help you nail this?

Samuel Shor, MD, FACP: We’re involved in the study of 2 tests that are very promising. One is called the Nanotrap, which looks at a highly specific protein called OspA that is found across multiple strains of Borrelia. And what this technology does is super concentrate, in a urine sample, the presence of this protein and then further tests it, and, it’s 1000-fold more sensitive than the standard Western Blot. In our 2015 paper that was published in the Journal of Translational Medicine, in the preliminary erythema-migrans patients—who are very often negative in the ELISA test because they haven’t had the time to respond immunologically—24 out of 24 were positive with the Nanotrap test.

Peter L. Salgo, MD: Let me play the devil’s advocate and say that when you make a test sufficiently sensitive, it may become insufficiently diagnostic. That is, everybody turns positive.

Samuel Shor, MD, FACP: No, it’s highly specific.

Peter L. Salgo, MD: Tell me about it.

Samuel Shor, MD, FACP: It’s highly specific, and as far as the authors of this study feel, the false positivity is very low.

Peter L. Salgo, MD: But does that mean that you’ve been exposed or that you’re actively infected?

Samuel Shor, MD, FACP: It’s an antigen, so you’re actively infected. There are studies to show that an infection should be cleared and no antigen should be present within 72 hours of that infection being cleared by the body.

Peter L. Salgo, MD: So, the obvious question that comes to mind is, if somebody who’s positive by that study is given appropriate antibiotics, improves clinically, does that study then become negative?

Samuel Shor, MD, FACP: Yes, it has. And, in fact, I provided the test to 100 patients with chronic disease, 42% of whom were positive, and 1 of whom was an MS patient who was symptomatic when she was first studied and asymptomatic when she was subsequently studied. She was positive initially and negative afterwards.

Peter L. Salgo, MD: All this suggests that patients with ongoing Lyme disease-related issues—and I’m being very careful with the syntax—often wind up with a lot of different doctors, a lot of different clinical situations. The provider path here is an issue.

Leonard Sigal, MD: Can we just return to testing here for a moment? Because that is a fascinating new technology. There is a polymerase chain reaction that’s available. It’s not often used, and it shouldn’t be used. It’s a research tool, but it’s not the sort of thing that the average clinician should be ordering. There was a technology that the late Michael Brunner and I worked on back at Robert Wood Johnson University looking for immune complexes. An immune complex can only be formed if there’s an antigen and antibodies against it. So, we concentrated on immune complexes, broke them up, and then looked for an antigen, OspA, as well as an antibody against Borrelia burgdorferi. We found it to be a remarkably useful tool in diagnosing people who had active infection, some of whom were seronegative, and people who had been treated and were now asymptomatic, because they had been treated appropriately and gotten rid of the Borrelia. The problem is that it’s a tedious sort of technology: very useful, but not easily done. And so, that’s what we’re looking [at] for now: a technology that’s sensitive and specific, which is a very difficult balance to manage, and a technology that can be ramped up to make it a commercial tool.

Samuel Shor, MD, FACP: We are actively involved in the FDA approval of erythema-migrans patients, to the goal of having a CLIA-waived in-office test with that technology. We have to keep in mind we’re 24 months away from that, but that’s the goal.

Peter L. Salgo, MD: Wouldn’t that be great. We wouldn’t be having this broadcast if we had the Lyme disease test.

Leonard Sigal, MD: Yes, we would.

Peter L. Salgo, MD: We’d have a different broadcast.

Leonard Sigal, MD: There are other things we could talk about.

Patricia V. Smith: I’d like to address this issue because it’s frustrating sitting here. I’ve been involved in this setting for 33 years, and I look at what has happened. You can all talk about these tests, and I certainly was going to bring up what Dr. Sigal mentioned because we had funded Dr. Schutzer at UMDNJ, who initially looked at those immune complexes. He actually proposed that test to the CDC, and they didn’t want to hear about it.

Peter L. Salgo, MD: Why?

Patricia V. Smith: Well, that’s a good question. What I’m saying to you is that the CDC is very reluctant to move on to new technology. I’ve been invited out there, twice, to Fort Collins. We’ve brought it up as advocates. The physicians have brought it up; researchers have brought it up. They want to stick with a 2-tier, antiquated test that, again, is probably missing at least 50% of our patients. So, for a lot of what we’re talking about, in reality, we’re not going to accomplish it unless the CDC moves off the dime.