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Lyme disease—who is credible?

I recently had a pleasant, brief email exchange with Kris Newby, the producer of the latest medical advocacy pic, Under Our Skin. There’s been a number of similar movies lately, mostly about quacky cancer therapies. This one is apparently much better made, and follows the controversy regarding “chronic” Lyme disease.

I’d heard an interview about the movie on Diane Rehm, and was rather unnerved by it. It sounded like a typical I-drank-the-Kool-Aid-now-I’m-gonna-make-a-movie kind of thing. Still, I haven’t written about it, because I haven’t seen the movie. That’s going to change. Kris is being kind enough to send me a copy, despite my warning that I’m very likely to pan it.

Anyway, in our conversation, she recommended that I check out a particular piece in the Journal of Medical Ethics. Before I go into the significance of this paper, let me give you a little background. Stick with me here, I’ll make it brief.

Lyme disease is a tick-borne bacterial infection common in many parts of the U.S. and Europe. In the U.S., it is especially common in the Northeast, but is present in pockets elsewhere. It usually presents with a rash, and sometimes progresses to joint pain and can have neurologic symptoms as well. These joint and neurologic symptoms can occur several weeks after the initial infection. There is also an entity often referred to as “chronic Lyme disease“. This entity isn’t widely accepted in the medical community, but is strongly advocated for by a vociferous group of patients and doctors who believe that Lyme disease can cause all manner of very late-onset symptoms.

The controversy is a nice model for many similar controversies: the science doesn’t support the existence of the disease, but a dedicated group of activists, including some scientists and physicians, feel their extensive experiences more than make up for lack of data. What some of us have problems with is not only the lack of data, but also the willingness of people who believe in this to go about trying to prove it in unconventional ways, for example, relying on lab tests that are not validated. It certainly doesn’t help their cause that they attract a lot of kooks, but of course, it doesn’t really matter how many kooks the chronic Lyme folks have on their side; what matters is data, and if their data are the most convincing, their hypothesis wins.

Now, as we talked about yesterday, good ideas don’t always win right away. But if these ideas come closest to the truth, win they will, no matter who or what stands in their way.

And the chronic Lyme folks certainly believe that there are dark forces arrayed against them. You see, these folks think that Lyme disease causes all sorts of problems, and that there are many solutions, including long term antibiotic therapy. The data so far do not support this hypothesis. And this is where it gets interesting.

Medical societies often put out consensus statements about the best science-based way to approach diseases. These statements are in no way binding, but they are often taken quite seriously. For example, the American College of Physicians, my professional group, has a number of statements on the proper approach to upper respiratory tract infections, such as colds and sinus infections. The articles on the recommendations are printed alongside the justifications and data. In this case, the data do not support the use of antibiotics for most sinus infections, at least in the first week or two. This is mildly controversial, mainly because patients often believe that an antibiotic will make them feel better. The evidence belies this.

So the Infectious Disease Society of America (IDSA) has recommendations on the treatment of Lyme disease, which are shared by all the other relevant mainstream medical societies, and these guidelines specifically recommend against the long term use of antibiotics for supposed chronic Lyme disease.

Now, it is a fact that at this point, the data support these guidelines. The vast preponderance of evidence has failed to show any benefit to the use of antibiotics in this setting. This of course does not guarantee that the guidelines are correct, but it certainly is the best we have for now. If and when evidence comes along that is good enough and plentiful enough to convince the medical community otherwise, the guidelines will change. It may not happen overnight, but eventually it will, because no “conspiracy” is vast enough to hide scientific truth for long. But some people are unconvinced. In support of their cause, they have created several organizations, at both the local and national level, and have enlisted various “experts”. One thing many of these experts seem to have in common is that they are not actually regarded as experts by the rest of the medical community. The other fact about these organizations and professionals is that they often go outside the scientific process to advocate for their ideas.

For example, these groups convinced the Connecticut attorney general to investigate the IDSA for alleged anti-trust violations. This is highly unusual, and the case was settled when the IDSA agreed to review, but not necessarily change, their recommendations. Part of the allegation was that there was a massive conflict of interest. You see, because the guidelines recommend against long-term antibiotic therapy, insurance companies often will not cover it. Some folks see this as a vast conspiracy. Others see the guidelines as saving patients from ineffective, dangerous and costly treatments.

So, in the mainstream of science-based medicine, this is essentially a non-issue. No significant evidence has yet shown up to overturn our current approach to Lyme disease. This hasn’t stopped the chronic Lyme advocates. And this takes us back to our movie producer and her suggestions to me. If you think way back to the beginning of this piece, you’ll recall that Kris recommended I check out a piece in the Journal of Medical Ethics. I did. I was impressed, but not for the reasons she hoped.

I have a strong interest in medical ethics, although I’m not an ethicist myself. Still, I’m generally familiar with the jargon and the writing styles. This piece reads like no ethics article I’ve ever seen. It is basically an advocacy piece for the concept of chronic Lyme disease, and starts from an entire set of problematic assumptions. First, the title: Attorney General forces Infectious Diseases Society of America to redo Lyme guidelines due to flawed development process
. That’s actually not true:

The main actions of the agreement include:

Complete resolution of the Attorney General’s investigations, issues, and potential claims and causes of action against IDSA and its volunteer panel members.

The current Lyme disease guidelines remain in effect. The medical and scientific basis of the 2006 guidelines remains in place and unchallenged.

IDSA will convene a review panel to determine whether the 2006 Lyme disease guidelines should be revised or updated. Howard Brody, MD, PhD, who has been jointly selected by the Office of the Attorney General and IDSA, will serve as an ombudsman who will have a limited role that will focus on screening potential conflicts of interest. The ombudsman will not be involved in the operation of the review panel. Any proposed changes to the guidelines would require a supermajority vote of 75 percent of the panel.

In other words, the IDSA agreed to change nothing in return for the CT AG returning to practicing law rather than medicine. Any ethics article that starts with a lie is unlikely to continue well. In fact, it goes on to assume as fact statements such as, “the diagnosis and treatment of Lyme disease has been suppressed, with profound healthcare implications for patients, their families and their communities.” This is not fact. This is opinion, and a controversial (and wrong) one at that. Now the paper uses this topic to explore ethical issues in conflicts of interest, the use of guidelines in general, and basically rehashes the “health care freedom” argument, which is basically a quasi-libertarian argument to allow patients access to any care, no matter how bad.

So, after reading this, I was curious: who are the authors? Are they infectious disease docs? Ethicists? Once I started looking at the first author, I was hooked.

His name is Dr. Raphael Stricker. He’s a hematologist, that is, someone who studies blood, blood banking, blood disorders, and the like. He is not an infectious disease specialist, the specialty that usually treats Lyme disease (although other specialties, such as neurology and rheumatology are not infrequently involved). Take a look at his CV, especially his research experience. You’ll notice that it seems to drop off after around 1993. Well, that’s not unusual. People don’t always stay in research forever. (Further down, he’s working for ILADS, the “chronic Lyme” advocacy group—curious). Anyway, further digging shows a possible reason for his drop off in research:

An investigation conducted by the University found that Dr. Stricker falsified data for a manuscript and a PHS-supported publication reporting research on AIDS. In the manuscript, Dr. Stricker selectively suppressed data that did not support his hypothesis, and reported consistently positive data whereas only one of four experiments had produced positive results. In the publication, Dr. Stricker reported that an antibody was found in 29 of 30 homosexuals, but not found in non-homosexuals. However, Dr. Stricker’s control data, which he suppressed, showed the antibody in 33 of 65 non-homosexuals. The falsified data was used as the basis for a grant application to the National Institutes of Health. The ORI concurred
in the University’s finding. Dr. Stricker executed a Voluntary Exclusion and Settlement Agreement in which he has agreed not to apply for Federal grant or contract funds and will not serve on PHS advisory committees, boards or peer review groups for a three year period beginning April 1, 1993. The publication “Target platelet antigen in homosexual men with immune thrombocytopenia” in the New England Journal of Medicine, 313: 1315-1380, 1985 has been retracted (New England Journal of Medicine, 325: 1487,1991).

Hey, he even made the New York Times!

So, in this debate about “chronic Lyme disease”, who is credible? Is it the experts in the field who have looked at the preponderance of data? Or is it a movie producer citing an ethics article which contains incorrect statements of fact and is written by a non-expert in the field who was banned from NIH funding for falsifying data?

Kris, you didn’t convince me to take you more seriously with your reading recommendations, but hey, I’ll still check out your movie. Hopefully it’s more entertaining than Expelled.

Posted in: Science and Medicine

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15 thoughts on “Lyme disease—who is credible?

  1. DevoutCatalyst says:

    The time to sort this all out is beforehand, not after a movie has been made. Someone like Michael Moore, who has a true gift, could become a superhero of a moviemaker if a few skeptics were employed as the go-to fact and argument checkers.

    The SBM crew (as well as the skeptical community in general) should hang out the proverbial shingle offering such services.

  2. weing says:

    Very interesting. I’m in Connecticut and have acquired a patient who is convinced he has chronic Lyme and is on Biaxin for it. He’s getting it from a specialist in a neighboring state. I went over his lab work and did not see anything to support an ongoing infection but I could not convince him that continued antibiotic use is not going to get rid of his symptoms.

  3. Khym Chanur says:

    From an article by Dr Scott Taylor:

    The diagnosis of Lyme disease is primary based upon clinical evidence. There is currently no laboratory test that is definitive for Lyme disease.

    So, then, is that the basis for the dispute? Does it go something like this?

    1) A patient shows the symptoms of Lyme disease, is given antibiotics, and the symptoms go away, so that proves that is was Lyme disease.

    2) A patient is diagnosed with chronic Lyme disease, is given antibiotics, and the symptoms go away, so the doctor reasons that the symptoms must have been caused by a bacteria.

    3) Someone else does a statistical analysis of the developmental histories of a bunch of chronic Lyme disease cases and reaches the conclusion that the antibiotics had nothing to do with it, and that it was just spontaneous remission.

    4) The doctors who diagnosed the chronic Lyme disease say that their clinical experience trumps statistical analysis.

    Also, why haven’t the supporters of the chronic Lyme disease hypotheses taken tissue samples from their patients and do PCR to look for the bacteria’s DNA? Find the bacteria’s DNA that way would be big evidence that they’re right.

  4. Eric Jackson says:

    Khym, that’s pretty accurate.

    I have a bit of an interest in the area of microbiology and antimicrobial therapy, perhaps in small part to being subject to UC Irvine’s seemingly all consuming anti-tuberculosis project.

    The essential problem with PCR testing for Borrelia DNA is the propensity for false negatives due to poor handling, the relative time consuming and expensive nature of the test and so on. We’ve seen occasions where PCR has been misused and then presented as evidence, notably in the MMR situation where shoddy handling by a lab with a poor history resulted in finding measles RNA in a person without any measles infection.

    It’s also worth noting that there was a vaccine available for Borrelia spp. sold by GSK for several years. It was fairly viciously assaulted, ironically by the Lyme Disease Association. LDA is an organization that promotes long term antibiotic therapy, and is guilty of the usual research mangling and selective quoting of research.

    Lyme has become something of a ‘red flag’, though not so severe as Candida or ‘Adrenal Fatigue’. Basically, it seems to have attracted the paranoid, irrational group, the sort who stalk about the internet and local newsmedia posting rants that are quite off the deep end.

    That said, I don’t think there’s ever been solid repeatable evidence of the presence of the Borrelia bacteria in cases of ‘chronic lyme disease’. There’s one case (PMID: 9861561) where this was claimed, however this claim accompanied the development of a ‘new’ media on which to culture the bacteria. Subsequent work (PMC87571) failed to show that this media was an improvement.

    Borrelia is a spirochete, and to generalize, these are rather difficult to culture. Treponema pallidum, the causative agent of syphilis, cannot be cultured with any modern techniques, short of using animals to host it. Borrelia can be cultured, though based on the media described in the above links, it’s got rather extreme nutritional demands. It does not as a rule live intracellularly, though it has been demonstrated to do so in vitro. It also seems to interact with a bewildering array of immune signaling proteins, including several TLRs. My understanding of immunology on the whole is pretty poor however. I’m an undergrad, as much as I’d love to, I can’t know everything, so I’ll leave this area alone.

    I don’t find it implausible that Lyme infection has done something to people who claim chronic Lyme, however based on the evidence that’s available (and that I’ve seen) it does seem to be the case that they are not chronically infected with the bacteria and need massive, constant doses of antibiotics. That’s an answer these folks clearly don’t want to hear.

  5. storkdok says:

    I looked into the chronic Lyme claims a couple of years ago when a woman came onto a mother message board claiming that all autism was caused by chronic Lyme disease. She then went on to claim a myriad of other diseases were caused by Lyme. After reading many journal articles and the IDSA’s information as well as several websites devoted to chronic Lyme disease, I concluded the same thing mentioned in the OP and the replies. But that didn’t convince this woman. At least she stopped posting every day about Lyme causing autism and scaring the heck out of the moms.

  6. colli037 says:

    The chronic lyme cranks also ignore the evidence that the antibiotics they advocate have some (modest) anti-inflammatory activity, so many of their aches/pains do get better on antibiotics.

    tim

  7. tobryant says:

    Lyme Testing: There must be a definitive test for Lyme. Glaxo had to have one to test the efficacy of the LymeRix Vaccine. Where is the test?

    Lyme Treatment: Lyme is not unlike Syphilis in its behavior and make up. There is such a thing as Chronic Syphilis so where is the guideline for that treatment. Shouldn’t the Chronic Lyme treatment resemble that protocol as a standard until Chronic Lyme is better understood or disproved?

    I have Chronic Lyme and I hated the movie “Under Our Skin”. All it did was try and instill panic in people who are already sick and vulnerable to making desperate choices.

    I am not getting treatment because when it comes to Lyme its like the entire medical community has lost its mind. I have settled for treating the symptoms. I am the daughter of a geneticist and grew up in my father’s lab learning about even handed scientific principles for testing and treating disease.

    The IDSA Guidelines scare me. The doctors who treat Lyme scare me. The treatments scare me and the fear and anger around the whole subject scares me. Nothing about Lyme resembles even handed scientific principles and more closely resemble hysteria.

    In NC several Lyme doctors have been brought before the medical board not by people but by insurance companies. Here in NC doctors are so afraid to be associated with the Lyme that they do not report positive Lyme test to the CDC. It reminds me of the days when HIV first came to NC and doctors routinely sent patients to anonymous testing clinic to fly under the radar of insurance companies.

    The IDSA may lack a moral compass in the case of Lyme but we have much bigger problem with the power in influence of insurance companies over our medical board and panels such as the IDSA. I feel we need legislation to keep insurance companies from lodging complaints against doctors to the medical board. There is an inherent conflict of interest there. That would be a good first step.

    One correction on your article – 4 members of IDSA Lyme Guidelines Panel where found by the CT AG to have been influence by Glaxo and Insurance companies in excess of 10K a person to write the guidelines “in a certain way” including the chair of the board. One panel member was kicked off the panel for refusing to conform.

  8. weing says:

    Based on my review of the literature, there is no such thing as Chronic Lyme. That does not mean you are not suffering, you are. Just as someone who survived meningitis suffers from a seizure disorder due to the meningitis. I would not consider him to have chronic meningitis and continue to treat him with antibiotics. He needs anti-seizure medications.

  9. daedalus2u says:

    There is such a thing as chronic syphilis; that was end stage There is such a thing as chronic syphilis; that was end stage neurosyphilis before there were treatments.

    Bacteria that are capable of forming chronic infections typically do so by hanging out intracellularly, often in the lysosome. Chronic inflammation reduces the effectiveness of the lytic enzymes in the lysosome by increasing the pH by inhibiting the ATP powered proton pumps that acidify the lysosome.

    Chronic oxidative stress or chronic inflammation will reduce the effectiveness of autophagy and the clearing of damaged proteins and also the clearing of intracellular infections.

    http://www.ncbi.nlm.nih.gov/pubmed/17389386

    Look also at the comment in Autophagy.

    If you click on the “related articles” link, # 7 demonstrates that a high ATP level is necessary for clearing intracellular TB. Inflammation lowers the ATP level by reducing NO levels which regulates ATP via sGC. In sepsis, the very high levels of NO (from iNOS) cause very high levels of ATP.

    My own thinking is that what is called “chronic Lyme” is actually simply chronic inflammation, sufficient to reduce NO levels and impede mitochondria biogenesis and cause chronic fatigue. I think the effect of chronic antibiotic use is due to several things, the placebo effect, anti-inflammatory effects of antibiotics, and a Herxheimer reaction from non-pathogens in the gut. This Herxheimer reaction (first observed in the treatment of syphilis) stimulates NO production via iNOS expression due to lysed bacteria killed by the antibiotic. This increased NO level makes people feel better until the iNOS is degraded in a few days, after which they get worse.

    I have a write up on Morgellons which I think is from chronic inflammation and low NO also.

    That “ethics” paper is so grossly wrong it should be retracted. I think the journal editors will agree if they look into it and will force a retraction. I only saw the abstract, so I didn’t see the authors’ conflict of interest statement.

  10. tommyhj says:

    Although a nice post, i did miss some numbers on what is understood as “chronic lyme” and long-term antibiotic treatment.

    Is it chronic if classical neurological symptoms occur 2-3 months after initial erythema migrans? Is 4 weeks of i.v. penicilin long-term? Because that would be normal Lyme disease behaviour and treatment at my university and hospital, and what we are taught in medical school (Denmark).

  11. heko says:

    A prominent Lyme researcher at my medical school has argued strongly against the diagnosis of chronic Lyme. When chronic Lyme was more prominent in the national news a few years back, protesters showed up at the clinic. It escalated to the point where extra security was considered for his safety. (I was told they were in fact hired, but since I heard that secondhand, can’t confirm it.)

  12. Prometheus says:

    Tobryant asks:

    There is such a thing as Chronic Syphilis so where is the guideline for that treatment. Shouldn’t the Chronic Lyme treatment resemble that protocol as a standard until Chronic Lyme is better understood or disproved?

    There is such a thing as chronic syphilis (Treponema pallidum) – it occurs when syphilis remains untreated for a period of years. The characteristic signs and symptoms of “chronic syphilis” (tertiary syphilis) are well documented – some get better with treatment and others (most) are unchanged (although progression of the disease stops with treatment).

    Where the comparison breaks down is that chronic or tertiary syphilis is treated by 14 days of IV penicillin followed by weekly injections of a long-acting depot penicillin for 3 – 4 weeks. The whole course of treatment is over in less than two months.

    Given that the causative organism (Borrelia burgdorferi)of Lyme disease is sensitive to penicillins and cephalosporins, I can see no reason why “chronic Lyme disease” should require any more intensive therapy than “chronic syphilis” (i.e. no more than two months of antibiotics). That so many people have been on antibiotics for years begs the question: what exactly do they think they’re treating?

    Prometheus

  13. Newcoaster says:

    I don’t have any patients with CLD, though I’ve seen several who think they have it. When I tell them I won’t prescibe long term antibiotics for that indication, and that the evidence doesn’t support the existence of a describable disease, or even a consistent syndrome….they go away angry and never come back.

    But is that really good medicine if they will just keep searching until they find some quack who will?

    I’m really starting to think there is a role for placebos in general practice medicine, to keep the patient around long enough to educate them more slowly.

  14. anthony lionetti says:

    i have found your article extremely interesting and consistent with a viewpoint which purports itself to be based on the complete and current medical evidence in relationship to the diagnosis of infections with Borrelia burgdorferi in humans. In fact if one reviews the peer reviewed medical literature all sorts of surprises emerge.

    The most recent IDSA guidelines were written by a consensus of a superselected group of like minded individuals. Regardless of the possible validity of their results, they must always be suspect to be biased. Highly controversial subjects should probable be subjected to a Delphi panel approach as suggested by the RAND corporation. This not being the case with the IDSA Lyme disease guidelines, the resultant controversy should be expected and perhaps may even be justified.

    Lyme disease has presented special challenges in evalauating diagnosis and treatment since the first North American papers were written by Steere et al in 1975. One must remember that the causative agent of Lyme disease was discovered by Willy Burgdorfer PhD at the RML in Hamilton, Montana in 1980. He was not associated with the working groups in the Northeast dedicated to finding it. Additionally that year those working groups were almost at press with a paper stating that they did not believe that Lyme disease was caused by a bacteria, but probably by a virus or some other particle ( they did not find a candidate bacteria, and they did not believe that the patients had responded to emperical antibiotic therapy as they would have anticipated).

    Lyme disease is touted to be ” easily diagnosed and treated”. The IDSA guidelines imply that the majority of patients have positive serological tests (by ELISA and Western Blot). This is not concordant with the primary research articles in the North American peer reviewed literature. This simply is not accurate. Please read the following papers which show statistical seroconversion rates (those meeting current Dressler criteria standards) to be somewhat lower than a clinician should accept for an acceptable negative predicitve value

    Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans.
    J Clin Microbiol. 1996 Jan;34(1):1-9.
    “Although most patients (89%) developed IgG antibodies to
    various B. burgdorferi antigens, only 22% of the patients could
    fulfill the criteria used for positivity.”

    Serodiagnosis in early Lyme disease.
    J Clin Microbiol. 1993 Dec;31(12):3090-5
    “Seroconversion was observed in 74 and 64% of evaluable patients by ELISA and IB, respectively, despite the use of antibiotic therapy.”

    Evaluation of two-test serodiagnostic method for early Lyme disease in clinical practice
    J Infect Dis. 1999 Apr;179(4):931-8
    However.only 12 case-patients (16%) ever developed an IgG response sufficient to meet the CDC-recommended WB criteria.

    All of these studies were in mainstream journals, represented patients well characterized to be infected with Lyme disease, not by Lyme arthritis, but by EM rash and Culture. The first two citations were coauthored by the chairman of the 2006 IDSA Lyme disease guidelines panel. The third citation was coauthored by the then head of the Lyme disease branch of the CDC. Neither were included in the bibliography of the guidelines panel. Perhaps this is just a small red flag.

    Might does not make right. I do not advocate that either “side” in this mortal combat are right, just that the peer reviewed medical literature is not being thoroughly evaluated, leaving good intentioned, but ill informed clinicians taking the side in a controversy which really moy not be as evidence based as they had hoped. Caveat emptor.

  15. joanne60 says:

    It should be IDSA proving that infection no longer exists. They can’t.

    I have been chronically ill with severe debilitating arthritis and muscle weakness treated on long term antibiotics and now pain free and with full mobility. All this following a tick bite athough I only discovered the connection retrospectively, inspite of seeking medical advice at the time.

    I know that each time I stopped, started, increased, decreased antibiotics my symptoms responded. Hardly anti inflamatory as at the start I was on steroids for wrong diagnosis which would likely be far greater anti inflamatory. I think the many months of antibiotics rather blows a theory in placebo. Interesting some antibiotics worked better on some symptoms others on other symptoms.

    My doctor suspected Lyme Disease after a favourable reaction to antibiotics. There had been other cases in the surgery treated in the early stages of tick bit EM rash and positive serology. Eventually I was clinically diagnosed and both Doctors have been happy to treat and pleased with my progress, albeit rather lengthy.

    I am lucky I had two thinking doctors and have recovered. Sadly whilst this becomes so polorised patients are sufferring.

    In medicine we need to be listening, no one can claim to know it all. Medicine continualy evolves so why such a strangle hold on this illness.

    Tests are not definitive unless you are able to get a positive PCR and how many of us can afford that privately.

    Good luck to those seeking help with their chronic health and wondering if it could be lyme you need to read much further than this sort of article.

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