Leonard Sigal, MD, explains his approach for treating Lyme disease patients with persistent symptoms.
Leonard Sigal, MD, clinical professor and former chief of the Division of Rheumatology at Robert Wood Johnson UMDNJ Medical School, explains his approach for treating Lyme disease patients with persistent symptoms.
Interview Transcript (modified slightly for readability):
“There are many potential explanations for why somebody has ongoing complaints after what should have been adequate antibiotic therapy. First of all, it’s possible that the patient didn’t take the antibiotics. You give them 2 weeks of doxycycline and they got 5 days [but now it’s] sitting in the medicine cabinet because they feel so much better. Why bother, right? [The thought is] so they’ll have the antibiotics for next time that they get bitten by a tick. This is not the way that we practice medicine. And so, it’s possible that they didn’t take the antibiotic.
It’s also possible that the antibiotic was not absorbed. There are some people for whom the diarrhea and abdominal pain from doxycycline are so great—and the same thing is true sometimes of amoxicillin—that they just flush it right through their system and it never really gets absorbed. There are other people for whom it’s not diarrhea, it’s just that they don’t absorb it; it’s possible.
There are people who had more advanced disease than you identified at the time you saw them. Let’s say that you see somebody with erythema migrans—the rash of Lyme disease—you give them oral antibiotics because it turns out that they already had meningitis; it was subclinical, you didn’t see it, you didn’t appreciate it. They come in 3 weeks later for a follow-up and they say, ‘My neck is so stiff and I’m feeling so weak.’ We can do a spinal tap if there are cells; you can also find antibodies against the organism, but if you find a lot of inflammatory cells, this is meningitis. This requires intravenous (IV) therapy, not oral therapy. And so, I didn’t give the appropriate therapy the first time through, not because of my incompetence, but because it was subclinical.
Assuming that you have given appropriate antibiotics and they were absorbed, some people will have persistence of organisms—presumably. That’s very ill-defined, as of now. But it is possible that there is a persistence of organisms. All of the organisms that have ever been identified, all the Borrelia burgdorferi, are sensitive to the antibiotics that we use; it’s not as though there’s a resistant strain out there. But it’s possible that it was in a cell someplace and the cell broke open and now, you’ve got the organism multiplying again. And so, in some sort of a privileged site, it’s possible—unproven, but possible.
The second potential explanation is debris, dead organisms lying there in a joint, as an example, and it’s a focus of ongoing inflammation because your macrophages are trying desperately to get rid of this residual stuff and it’s very indigestible. And so, there’s ongoing inflammation; that’s ongoing symptoms, despite. It’s possible that you might have debris elsewhere in the body and have inflammation and inflammation is causing your symptoms—global inflammation, systemic inflammation.
It’s possible that what’s going on in the patient is immune in mechanism, that somehow the infection has caused an immune response, not necessarily autoimmune, but an immune response, an ongoing inflammation, and so, it just can’t be tamped down. It could be autoimmune; I must tell you that Alan Steere looked at autoimmunity due to B. burgdorferi outer-surface protein (OspA), or centered on OspA. I think that has been demonstrated to not be of any clinical relevance.
My laboratory, when I was at Robert Wood Johnson, looked at neurologic disease. We found cross-reactivity between a Borrelia burgdorferi antigen and a human antigen. The possibility of autoimmunity was raised. We demonstrated it in the laboratory; I don’t know that we have ever seen that be of clinical relevance, but it’s possible. There’s no evidence to suggest that it happens, but it’s possible. Ongoing immunity, autoimmunity, maybe.
The final explanation is that the patient once had Lyme disease but something else is going on now. As I said before, Alan Steere has shown that there are people who have chronic inflammatory diseases that have nothing to do with Lyme disease, that follow Lyme disease. Life does not come to a screeching halt medically when you eradicate Borrelia burgdorferi; other things can happen. Are they causative? Is it that the B. burgdorferi caused rheumatoid arthritis? There’s no reason to believe that’s the case, but it happened.
And so, it’s very important that you not assume. Remember the old expression, ‘When you assume, you make an ass out of you and me?’ It’s very important that you not assume that something that happens after Lyme disease, is, therefore, due to the preceding Lyme disease. You have to have an open mind about this. What you need to do is approach the patient, with the Lyme disease in the background, but look for other potential explanations. Does this lady have Lupus? Does this lady have rheumatoid arthritis? Does this lady have amyotrophic lateral sclerosis? And then, there’s always the very real question: Was the initial diagnosis of Lyme disease correct? Very frequently, in a referral practice, you’ll see somebody come in with a diagnosis of Lyme disease that I can’t substantiate; I don’t know how that diagnosis was made. When I start digging through the records, there’s [nothing there to indicate it]. And so, it’s very important that you be sure that there’s really a Lyme disease diagnosis that is supportable in the first place. But even if there was, look for other things to make sure that you don’t miss something. Because the diagnosis of chronic Lyme disease is almost a diagnosis of exclusion, and a diagnosis of exclusion is a very difficult thing to do because it means that you’ve excluded everything else? Not the easiest of practicing medicine.”