Reaching a Consensus in Lyme Disease

Peter L. Salgo, MD: Moving to consensus: yes or no? The first step, if you’re going to make the diagnosis and treat it, is 2 to 4 weeks of antibiotics to kill the spirochete. Yes, no, what?

Robert C. Bransfield, MD, DLFAPA: No.

Peter L. Salgo, MD: No. Bob, why not?

Robert C. Bransfield, MD, DLFAPA: Well, I think I’ve seen some people for whom that works, but I think there’s always the outlier in the bell curve. There are some people where a few weeks do not work for some reason. Maybe they have a complex infection. There’s more than one pathogen.

Peter L. Salgo, MD: I said first step, would that be the first step for most people?

Robert C. Bransfield, MD, DLFAPA: Yes, I think that would be.

Leonard Sigal, MD: That would depend on the manifestation though. If somebody comes to you with meningitis, you’re not going to give them 2 weeks of doxycycline.

Robert C. Bransfield, MD, DLFAPA: No.

Samuel Shor, MD, FACP: No, but you’re not going to give them more than 8 weeks probably.

Leonard Sigal, MD: But my point being is that it depends.

Robert C. Bransfield, MD, DLFAPA: You’re right, it depends.

Samuel Shor, MD, FACP: Yes.

Peter L. Salgo, MD: OK. Consensus or not—my guess is going to be no, by the way—what do we do for the subset of patients who continue to experience symptoms after this 2 to 4 to 6 weeks of antibiotics?

Samuel Shor, MD, FACP: Careful differential diagnosis and careful empathetic review of their clinical picture.

Leonard Sigal, MD: And not telling them that it’s all in their head.

Samuel Shor, MD, FACP: Right, and being supportive.

Leonard Sigal, MD: Absolutely.

Samuel Shor, MD, FACP: With the recognition that there are going to be those of us who feel a greater percentage of patients probably have active infection as opposed to another group of people who do not, such that the recommendations coming out of that review is going to be different.

Leonard Sigal, MD: And to reiterate, looking for other potential explanations.

Samuel Shor, MD, FACP: Differential diagnosis.

Leonard Sigal, MD: Absolutely.

Robert C. Bransfield, MD, DLFAPA: And don’t just give antibiotics to treat the symptoms as well. We need to do both.

Peter L. Salgo, MD: Let’s boil it down. I’m trying to get at least some clarity, here, for the rationale for or against using a longer course of antibiotics in patients who have persistent symptoms.

Samuel Shor, MD, FACP: If you feel that there is a threshold that you’ve achieved and that there is active infection—and we’ve all discussed what that means, and that threshold is different for individuals. If you feel that’s the case, then by not doing that, you potentially run the risk of not having adequate therapeutic gains. The other component—and this goes to the MS patients. A number of them, actually all 3 of them, were recommended by the neurologists to be on immune-suppressive drugs, which could have made their conditions worse had they not been identified as having an infection.

Peter L. Salgo, MD: Now, we’ve had an awful lot of bomb-throwing here today. There’s an awful lot of grenades flying through the air out there. What do we need to reach a better consensus on the issues that we’ve discussed?

Samuel Shor, MD, FACP: Better testing.

Peter L. Salgo, MD: Better testing. What kind of testing are we looking for?

Leonard Sigal, MD: Let’s back up for a second. We need better science, looking at clinical markers, biomarkers as you were saying; looking at better testing; and looking at what the sensitive questions are that we can ask. I don’t mean sensitive in the sense of, “I’m caring for you,” that’s important, too, but sensitive in the sense of statistics. I think what we need to do is put down the grenades, put down the bombs, stop accusing each other of somehow having nefarious interest, and let’s have a civil conversation. I realize this is the United States in the year 2017, so the word civil has been thrown out the door. But maybe in this microcosm, we can be civil, have a conversation about this, and make the best of everybody’s talents and experiences.

Robert C. Bransfield, MD, DLFAPA: One solution is having more programs like this. This is great. I think when it’s face-to-face and collegial, we can help to reconcile these differences and iron them out. We’re coming at it from very different angles.

Leonard Sigal, MD: Yes.

Samuel Shor, MD, FACP: Right.

Robert C. Bransfield, MD, DLFAPA: I think this is very useful and I think better disease definition is critical.

Patricia V. Smith: I was just going to say that, over the years, many times, we have asked to have more dialogue. We’ve contacted the IDSA, we’ve tried to sit down with them. We actually had them at our LDA Columbia CME Conference several years ago. It was the first time they were on the same stage. Believe it or not, we’ve advocated for that for decades, to get people together to have a discussion. But, unfortunately, there’s been unwillingness, and I was very happy that Dr. Sigal agreed to come in today and sit at the same table as us, because it doesn’t happen very often.

Leonard Sigal, MD: But it goes the other way around, you know. I’ve invited people.

Patricia V. Smith: Excuse me, but who?

Leonard Sigal, MD: I’ve invited clinicians in New Jersey, who see hundreds of patients with Lyme disease, to sit down with me to come up with research studies that would allow us to understand what’s going on in those people, understand how they respond to antibiotics, and understand what biomarkers might be useful. And the last time I saw them was when they walked out the door. They didn’t follow through on their interest.

Patricia V. Smith: The reason for that may be because, for a number of decades, our physicians have been gone after by medical boards just for treatment, long-term, of patients with Lyme disease. That has been very problematic, and we have a number of physicians who have had sanctions and so on, so a climate of fear has existed. If they’re really the practicing physicians, they don’t want to put themselves out there, because they are brought up on charges.

Leonard Sigal, MD: Well, I’m not sure that’s the explanation. The BME, the Board of Medical Examiners in the state of New Jersey, has looked at many, many clinicians.

Patricia V. Smith: I know what they look at.

Leonard Sigal, MD: Yes, you know, unfortunately. But what I was asking was, “If you see these patients, let’s do a clinical study so we can understand what’s going on with these patients,” and they were never forthcoming. All I can do is invite and, in a civil manner, try to encourage them to be part of a scientific trial.

Patricia V. Smith: I think part of the problem is also that when there have been clinical trials—and sometimes the treating physicians have supported those trials, and they have said to patients, “Maybe you should enter those trials”—those trials always end up that the patients are basically not being helped by antibiotics. Again, broad brush conclusions. And so, those physicians and those patients don’t want to even participate in those trials.

Peter L. Salgo, MD: Let me see if I understand that point. There are trials that are undergoing, that are underway, and patients get enrolled in these trials, but the results are that antibiotics may not be the right answer. They didn’t give you the answer you wanted. Does that mean that the trial was bad?

Patricia V. Smith: No, that isn’t the situation. The conclusions that were drawn in some of these studies, in the 4 from the NIH—and Sam alluded to 2 of them before—were broad brush. It should have said that in this subset of patients who were in this trial, with these particular antibiotics for this duration of therapy, the antibiotics maybe did not help them—or in 2 cases antibiotics actually did, but they said that they didn’t. So, that is the broad brush.

Leonard Sigal, MD: One of the criticisms that I’ve heard of the “long-term” antibiotic trials is that the duration was insufficient, and had there been a longer trial of antibiotics, there might have been a better outcome. I’ve heard this from other people. I’m not putting words in your mouth, Sam. I just want to ask you about it.

Samuel Shor, MD, FACP: And that is a potential, but there are other confounding variables, such as in the Klempner study. Most people were sick for between 4-and-a-half and 5-and-a-half years, many of whom had gone through the very protocols that were used in the study, so you’re self-selecting failure. And it’s also a matter of not identifying treatment of co-infections.

Leonard Sigal, MD: See, you’re taking issue with the design of the study.

Samuel Shor, MD, FACP: Yes.

Leonard Sigal, MD: Had the study been a little bit more real-world oriented…

Samuel Shor, MD, FACP: Right. The problem is that you’ve got to control your variables, and there are so many variables that you’ve got to control.

Robert C. Bransfield, MD, DLFAPA: And PCR-positive patients were excluded from the study. They should have been the ones that were studied.

Leonard Sigal, MD: I agree with you.

Peter L. Salgo, MD: It sounds to me—not being involved in the creation of these studies, not being at the table—that if everybody got together and agreed a priori on the construction of the study and the goals and endpoints, everybody might agree better when they got the data.

Samuel Shor, MD, FACP: We’re in the process of actually doing that. There’s a work group of about 15 of us who are trying to put that together.

Leonard Sigal, MD: If I can be of assistance, let me know.

Peter L. Salgo, MD: I just want to point out, I haven’t seen this since the United Nations was formed.

Leonard Sigal, MD: In the pharmaceutical industry.

Samuel Shor, MD, FACP: Both schools of thought are involved.

Leonard Sigal, MD: In the pharmaceutical industry—and that’s not a dirty word—when you have a study of say a drug for rheumatoid arthritis, you have to come up with entry criteria that bring in patients who are as homogenous as possible, because you’re going to be randomizing them. If you randomize them and they’re not homogenous, you stand a chance of asymmetric distribution of patients and your study goes up in smoke.

Samuel Shor, MD, FACP: Right.

Leonard Sigal, MD: I’m not defending anybody’s study design, by the way. I’m just saying that when you do a study, you have to be really rigorous about bringing in as homogenous a population as possible. Now, for some reason, they decided to exclude PCR-positive patients. I don’t know what the reasoning was there. But the idea is to not make the entry criteria so small that you can’t get the real world in, but not so broad as to make it a garbage study. There has got to be some middle ground.