Challenges in Making a Lyme Disease Diagnosis


Peter L. Salgo, MD: Let’s make the diagnosis by simple, basic medicine. Geographic considerations, you’ve already told me that it’s more widespread than it’s thought to be. Are there some areas where there’s more likely to be Lyme disease than others?

Patricia V. Smith: Yes, according to the studies out there, that is true. However, unfortunately, many researchers feel that Lyme disease is actually far more widespread than the map shows. They are doing research in the South, for example, looking at the fact that it might be the Lone Star tick (Amblyomma americanum) that is actually carrying the disease. There has been research done by Kerry Clark at the University of North Florida in this area. So, I don’t think we can limit it, but yes, there are what are called high-incidence states; that’s the term that the CDC uses.

Peter L. Salgo, MD: It tends to be—right now at least—northern tier, the Northeast, and maybe spreading West.

Patricia V. Smith: There are about 14 states or so.

Robert C. Bransfield, MD, DLFAPA: There’s one interesting disparity when you look at human studies versus dogs. With, you see different geographical patterns. For instance, Colorado has a lot of dogs that are infected with Lyme disease, but people aren’t. So, it doesn’t exactly make sense that, maybe, the veterinary statistics are more accurate than the human statistics.

Peter L. Salgo, MD: Maybe people are getting missed or maybe the dogs are overdiagnosed.

Patricia V. Smith: Or maybe the dogs are invading an area that people just don’t go to.

Peter L. Salgo, MD: Right, because dogs are always in the brush. But that being said, I just want to nail this down before we go further. We’ve got geographic considerations; we’ve got some veterinary considerations. If you want to make this diagnosis, without the blood test for a moment, you’ve got to do a history and a physical. What are you going to find?

Samuel Shor, MD, FACP: Well, in keeping with that question, it involves the art of medicine and clinical judgment. You’re using risk factors for exposure. Those risk factors for exposure involve travel or location within a high-risk environment, recognizing that you can still contract the disease in low-risk environments. But it is a risk stratification. You’re exposing yourself to a habitat that is high risk: grassy areas, low brush, that type—such as walking through the backyard.

Peter L. Salgo, MD: Mind you, I’m not coming to your house any time soon.

Leonard Sigal, MD: Right.

Samuel Shor, MD, FACP: And then you have a clinical presentation.

Peter L. Salgo, MD: That’s what I’m driving at.

Samuel Shor, MD, FACP: It is consistent with the disease. Now, the challenge with that is this is the new great imitator, and it is also felt to be a neurotropic condition. Neurotropism means it’s drawn to the nervous system. So, for example, in the chronic fatigue syndrome paper that I published, chronic fatigue is one of the most common clinical presentations of the condition that has not been treated, and frankly, in some presentations that have been treated. But that’s another set of issues we’ll get to.

There are arthralgias, arthritis in a migratory pattern, very often. So, it goes from one joint to another with or without inflammation. The nervous system, whether it be neuropsychiatric or cognitive—the autonomic nervous system—is very often involved, and what I mean is the part of the nervous system that controls unconscious function: blood pressure control when moving from a lying to a standing position. Sleep—fractured, nonrestorative sleep—is a very common phenomenon, so you look at the complex symptoms with which an individual is presenting. You look at the risk factors for that individual’s exposure. Tests may be supported, but not required, because they're relatively insensitive.

Robert C. Bransfield, MD, DLFAPA: The key thing with any medical diagnosis is pattern recognition. You do a thorough assessment, you take a thorough history, and you do the old-fashioned medical school review of systems that we were taught to do that’s boring and tedious. That’s how you have to do it.

Peter L. Salgo, MD: But if I believe him, the review of systems for Lyme disease is essentially positive.

Robert C. Bransfield, MD, DLFAPA: No, no, I ask over 300 questions whenever I see a patient with Lyme disease. And I look at each one with a baseline or course of illness, and I have to do a very thorough review of systems. You see a certain pattern that evolves; it’s a multisystemic illness that can evolve over time. There aren’t too many multisystemic illnesses like this, so you look at what other pattern it correlates with. For every other setting in medicine, you do a thorough workup and review of systems. You don’t just rely on 1 piece of evidence, just 1 lab test. Why should Lyme disease be an exception?

Leonard Sigal, MD: But we’re talking about a very broad spectrum here. My colleagues are talking about people who are very ill for a long period of time and have symptoms that have somehow evaded prior clinicians. There are people, on the other hand, who present with erythema-migrans. That’s pretty obvious. We can’t use that as the gold standard, as you pointed out, but it’s pretty obvious. If somebody comes in with a facial palsy in an endemic area, your index of suspicion is very high. That is something that is reversible with antibiotics, relatively quickly. These are all obvious things: lymphocytic meningitis in the proper setting, a heart block that progresses from a first- to second- to third-degree block in front of your very eyes. I don’t know of anything else that does that, and that’s also potentially very responsive to antibiotics, and relatively quickly.

And of course, arthritis, the monoarthritis, is not very painful, but it has a very large effusion. That’s quite often Lyme disease in the proper geographic setting and proper individual setting. And then, we move on to all of these less well-defined, very troublesome, and very difficult-to-identify-a-cause symptoms. There, the index of suspicion has to be high enough for you to actually say, “Well, I don’t know that this is Lyme disease, but if it is, I want to make sure that this person is treated.” We’ve all seen patients where it’s a balancing act, and you’re saying to yourself, “Gee, I’m not sure, but do I really want this person to walk out of this office without having been treated appropriately for Lyme disease if I think there’s a reasonably high level of likelihood?” The question is, what’s the reasonably high level of likelihood?

Samuel Shor, MD, FACP: And that’s a difference of opinion between different providers.

Leonard Sigal, MD: Precisely.

Samuel Shor, MD, FACP: I’d like to take that concept one step further. If I feel that, clinically, an individual raises to that level of suspicion where I’m concerned, then I will try a therapeutic trial of something like minocycline, 100 mg twice a day, for a month and see what kind of response they have. Are they getting better? Are they getting worse? When they get worse, there is a phenomenon called the Jarisch-Herxheimer response, which is an inflammatory response that is related to an introduction of, or change in, antibiotics that was characterized in syphilis.

Peter L. Salgo, MD: I was just going to say, yet another spirochetal issue.

Samuel Shor, MD, FACP: Another spirochete.

Leonard Sigal, MD: When you said minocycline, did you mean minocycline or doxycycline?

Samuel Shor, MD, FACP: I use minocycline. I prefer minocycline because of its CNS penetration improvement.

Leonard Sigal, MD: Are you aware of any proof that Jarisch-Herxheimer reactions can occur after the first, second, third, or fourth antibiotic?

Samuel Shor, MD, FACP: There are studies that support the finding of Jarisch-Herxheimer in Borrelia.

Leonard Sigal, MD: There’s no question about that, but my question is about how there are patients who say, “Well, I’ve had multiple Herxheimers.”

Samuel Shor, MD, FACP: Yes.

Leonard Sigal, MD: And I’m not aware of there being any proof that that phenomenon really occurs after the first, second, third, or fourth course of antibiotics.

Samuel Shor, MD, FACP: In the paper that I published, I do describe that.

Leonard Sigal, MD: That’s described by the patient.

Samuel Shor, MD, FACP: Yes.

Peter L. Salgo, MD: We’re going to get back to this. I promise you we’ll get back to it.

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