Oct 04 2007

The NEJM Takes On Lyme Quackery

I am a practicing neurologist in CT, which is practically at the epicenter of Lyme disease in the US (in fact, the disease is named after Lyme CT where it was first described). So I have seen my fair share of Lyme disease and a form a late Lyme disease known as chronic neurolyme. It is without a doubt a real and serious disease. However, it is also the basis for what I consider to be a fake disease, chronic Lyme. I was therefore very happy to see an excellent article in the New England Journal of Medicine critically analyze this troublesome fake syndrome.

Throughout history there has always been a number of popular fake diseases or syndromes – although the specifics have changed over time. Sometimes the disease is completely fictional, like electromagnetic hypersensitivity. Sometimes the diagnosis is really just a name being applied to a laundry list of non-specific symptoms, like “asthenia,” (a diagnosis popular a century ago). And often the fake diagnosis is based upon a real disease but overextends the diagnosis to incorporate those without the specific symptoms of the disease but who have nonspecific or vague symptoms. In this latter category I would place chronic fatigue syndrome, fibromyalgia, and chronic Lyme.

The phenomenon of the fake diagnosis is driven by several realities, most importantly that people often have symptoms for which there is no established diagnosis or where the diagnosis is undesirable. People often suffer from what we call “symptoms of life,” meaning common aches and pains that plague everyone, increasingly as we get older. Often people can get joint or muscle pain, headaches, fatigue, mild forgetfulness, and vague bowel symptoms without there being a specific underlying disease or disorder. The human machine is imperfect, it wears out over time, and these minor ailments are an unfriendly reminder of our frailty and mortality.

These symptoms can range from annoying to debilitating, and it is understandable that people want to minimize and avoid them. It is reasonable to seek a professional opinion when a new such symptom appears, and to seek symptomatic relief and also to pursue methods to stave off the onset of symptoms.

But sometimes people are not happy with this approach. For some reason they are convinced that there is a specific underlying disease attacking their body and this disease must be diagnosed and cured. Sometimes this is in fact the case, but when all such possibilities are ruled out and the symptoms are non-specific and do not point to a particular disease, the simple explanation of “wear and tear” is appropriate. Unwilling to accept this, many patients (often referred to as the “worried well”) create the demand for a label to attach to their symptoms of life, and thus are borne the wide variety of fake diagnoses to meet this demand.

Another source of this demand are those patients who do have a specific underlying disorder, but it is unrecognized, or they are unhappy with the answer. A common underlying problem is sleep disorders. Chronic sleep deprivation can cause fatigue, muscle aches, and even poor concentration and memory. Also, depression and anxiety can lead to the onset or exacerbation of common symptoms but some patients may find these diagnoses unacceptable or stigmatized, or may misinterpret them as a dismissal of their symptoms.

In the early to mid 20th century one of the more common fake diagnoses was tertiary syphilis. Obviously syphilis is a real disease, and it does have a chronic form that can involve the nervous system. It is also a great mimicker, meaning it can manifest in many ways. This is a good setup for a fake diagnosis – eventually any bizarre or non-specific syndrome was blamed on syphilis. It was the favorite diagnosis of quacks of the time, and the target of many snake oil claims.

It is probably not a coincidence that Lyme disease is also caused by a spirochete (a type of bacteria), as is syphilis, and that both diseases have a late neurological phase, and that both have a wide range of possible symptoms. What happens is that cases are reported where a patient has some weird syndrome and goes undiagnosed for a time and in the end it turns out they had syphilis (or Lyme disease) the whole time. This leads clinicians to think – “Hey, maybe my patient with a weird and undiagnosed list of symptoms also has syphilis/Lyme disease.” (Or, of course, the patient may follow this line of reasoning themselves.) It’s really that short a trip to the creation of a fake diagnosis. Throw in a little confirmation bias, a couple of logical fallacies, and you’re home.

With Lyme disease the story is very typical and instructive. Lyme is an infectious disease, so there should be some symptoms and signs of infection. There are also specific laboratory tests that can confirm the diagnosis – a Lyme titer, which looks for antibodies to Borrelia burgdorferi (the spirochete that causes Lyme in the US) or a Lyme western blot – a more specific antibody test. Finally, there are antibiotics to which B. burgdorferi is sensitive, and if treated aggressively and long enough should eradicate the infection.

But the Lyme phenomenon, like syphilis before it, has taken on a life of its own, propelled by patients in search of a diagnosis and by misguided or unscrupulous clinicians. There are many people walking around today with the label of Lyme disease who do not have, and never had, any signs or symptoms specific for infection or of Lyme, who have a negative antibody titer, and who have not responded typically to antibiotics. Then how can anyone say they have Lyme? Good question.

Physicians who have made this diagnosis have fallen prey to the “invisible dragon” fallacy – or systematically rendering a hypothesis (in this case a diagnosis) unfalsifiable. What they are saying, in essence, is that their patient has an atypical presentation of Lyme that lacks all the specific signs, that it is seronegative (the antibody tests are negative) and it is resistant to standard treatment. I submit that Occam’s razor would favor the alternative hypothesis that the patient simply does not have a Lyme infection. This NEJM review article also comes to the same conclusion.

The story of Lyme, however, has been made more complex by the modern quack innovation of the fake diagnostic test to support the fake diagnosis. For example, there are labs that will run their own Lyme serological tests that show Lyme where none exists. Their tests have not been validated, or they use low thresholds for positivity that are guaranteed to cause false positives.

Another example is the SPECT scan – single positron emission computed tomography. This is a scan that creates a map of blood flow to the brain. It has legitimate uses, but some Lyme true believers can see in the blobs of computer generated color the telltale signs of neurolyme disease – again without any validation. How more difficult is it for the public to distinguish scientific medicine from this slick imitation, when the purveyors of fake diagnoses have laboratory tests and fancy imaging studies to back them up?

Before one is tempted to claim that making such a fake diagnosis causes no harm and serves to comfort the patient, or that it is worth a try to treat for possible Lyme even in the absence of clear evidence – let me assure you that there is real harm. First, making a fake diagnosis often results in the premature end to the search for the real diagnosis. I have seen patients settle on the diagnosis of Lyme disease when in fact they had something else entirely – something that therefore went untreated.

Also, the treatment for chronic Lyme is far from benign. It usually involves months or years of chronic oral or intravenous antibiotics, with real risks and side effects.

It is also important to point out that the question of whether or not co-called chronic Lyme disease responds to long term antibiotics is a separate and specific question that has been addressed by research. The NEJM study also reviewed this evidence and concludes that antibiotic treatment for chronic Lyme is not effective.

This is a very important distinction. I often teach my students that whether or not a patient has a specific diagnosis is often not definitively answerable, and may be a matter of definition. But further, it is actually a proxy question. The real, and far more important question, is whether or not a patient meeting certain objective criteria would benefit from a specific treatment. So we can put aside the question of whether or not patients can have atypical seronegative treatment-resistant chronic Lyme disease and ask instead, do such people respond to any treatment. The answer, according to this review, is no.

It is also worth pointing out that there does seem to exist a real, if rare, post-Lyme syndrome – people who have persistent symptoms after treatment for Lyme disease. These represent the vast minority of patients diagnosed with chronic Lyme, and they don’t respond to antibiotic treatment either.

It remains to be seen what effect, if any, this review published in a prestigious journal by recognized experts will have on the chronic Lyme subculture. I predict none. The evidence and arguments were all already there. Also, the chronic Lyme true believers are a self-selective group that have already proven resistant to logic and evidence.

But this article is an excellent reference for the practicing physician or patients suffering from chronic symptoms. It also makes my job easier, at least in reference to this specific form of quackery.

Perhaps the most important lesson in this whole affair (and the one most likely to be overlooked) is that it demonstrates that it is possible for so many patients and practitioners to fool themselves for so long. Often belief in a phenomenon is used to justify the existence of the phenomenon, using the “where there is smoke there is fire” logic. But often the smoke is just an illusion, or an artifact of sloppy thinking. The story of chronic Lyme adds one more historical example of this, a cautionary tale for anyone putting forward their own pet unfalsifiable hypothesis.

__________

This article is also reviewed by Mark Hoofnagle over at denialism.

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15 responses so far

15 Responses to “The NEJM Takes On Lyme Quackery”

  1. jonny_ehon 04 Oct 2007 at 4:27 pm

    At what point do you declare that someone has a new disease or syndrome? If they have x, y and z symptoms, that don’t fit any known disease, does that mean it’s ‘wear and tear’ or psychosomatic? It sounds like there’s a thin line here.

  2. Steven Novellaon 04 Oct 2007 at 5:18 pm

    What Jonny is really asking is how do you know when someone has a discrete disease or syndrome, as opposed to just a collection of symptoms. There are several ways. You can identify a specific syndrome – meaning a set of symptoms that occur together in different individuals. One or more of the signs and symptoms must be specific enough to conclude that this is not just a chance occurrence of common symptoms. So fatigue and joint pain is not a discrete syndrome, having a rash in the shape of the letter “H” over your left scapula while your tongue turns blue is.

    That is the bear minimum. That is where the process of identifying a new disease starts. It has to be something recognizable.

    From there we try to describe the syndrome epidemiologically – who gets it, what is it associated with, etc.

    Next we identify biological markers – what blood tests are abnormal, etc.

    And in the final stage we learn about the pathophysiology – what causes it, what physiological, biochemical, anatomical, hormonal changes occur, what is its natural history.

    At any point in this process we can look at specific treatments to see if they work, but understanding the pathophysiology really helps.

  3. EmilyBon 04 Oct 2007 at 10:45 pm

    Dr. Novella,
    I am unclear from your first two paragraphs- are you saying that you think fibromyalgia and chronic fatigue syndrome are fake diseases? Or just that people are being diagnosed who don’t actually meet the criteria?

  4. Steven Novellaon 05 Oct 2007 at 7:39 am

    The latter – they exist but are way overdiagnosed based upon vague and nonspecific symptoms.

  5. JoHon 05 Oct 2007 at 8:23 am

    When I hear about Lyme, I’m always reminded of an anecdote told by my uncle (who became quite paranoid of ticks as a result). Apparently he knew a guy who was completely paralyzed by Lyme disease. Is that really a possible outcome?

    Regarding “tertiary syphilis”, I remember that I’ve been somewhat surprised by the number of famous historical people who were claimed to have suffered or died from “syphilis”. Not that I have kept statistics or something, lol. It’s just that it is linked to sexual promiscuity I guess, and biographers or websites with biographies are eager to point out that a historical figure was linked to it.

    Do you think it is likely that this was caused by the type of popular fake diagnosis you mentioned? I.e. most of these people were diagnosed with “tertiary” syphilis and not necessarily the other, more easily identifiable type/stage?

  6. dhmspectoron 14 Oct 2007 at 12:50 am

    Dr. Novella,

    I’m not one of the “chronic lyme” believers although I had a very nasty case of it over 2 yrs ago when I was 42. I am not sure that Lyme is a disease that either as easily diagnosed or as easily treated as one might think. Lyme, if you don’t get the bulls-eye can behave like all sorts of garden variety aliments: A touch of the flu, some joint pain that acts a lot like carpal tunnel or other repetitive-stress injuries, a sinus infection… unless you’re specifically looking for it, it can hide out until you have an experience like the one I had:

    I never got the classic bulls-eye rash, I never knew I had been infected. I got what I thought was, and looked like, a sinus infection – my GP prescribed a course of antibiotics. After several days when the symptoms didn’t start to get better, I went back in, we changed antibiotics, the next day I started to go numb on the left side of my face… back to the GPs office where and in my case, things took a sudden scary turn as my blood pressure was up through the ceiling (from 120/70 to 210/100 in 18 hrs)… they put my on beta blockers immediately and sent me for an immediate MRI to make sure I wasn’t stroking. No signs of a stroke.

    The next day my GP spent the day reviewing all my records for the previous two years and suggested the Alyssa and Western Blot be performed to see if I had Lyme (as well as tests for Erchliosis and Babesiosis). When the tests came back the Lyme titer was off the charts plus an added bonus of Erchliosis just to make things interesting.

    It took 4 30-day courses (with testing after each course) of doxycyclin to knock out the Lyme and the Erchliosis; the Bell’s Palsy was scary, and the Trigeminal Neuralgia and joint paint were unbelievably painful.

    Now, almost 2-1/2 yrs on I still am partially paralyzed from the Bell’s, and cold weather plays havoc with my joints. Since I live on Long Island (as you know being from CT, another Lyme hot-spot) and am outdoors a lot, and even though I practically make love to my spray-bottles of DEET, I have myself tested twice a year to make sure I haven’t gotten re-infected.

    The bottom line is that there may not be any such thing as “Chronic Lyme Disease” but Lyme is 1) Easily contracted; 2) Easily misdiagnosed – between 40%-60% of people eventually diagnosed with Lyme never get or see the bulls-eye rash; 3) Carried by more than just the deer tick; and 4) Can lie hidden for quite a while before those little spirochetes chew on enough of your various nerve tissues to damn near kill you.

    Moral of the story: anyone living in Lyme prone areas who spends time outdoors should have themselves periodically tested for both Lyme and the other common tick-borne diseases (like STARI, Erlichiosis, and babesiosis).

  7. Steven Novellaon 14 Oct 2007 at 1:04 am

    Dhmspector,

    Thanks for the comment. Actually what you are describing is a fairly typical case of neurolyme, minus the rash. You had a Bell’s palsy (I have personally never seen a case of neurolyme without a Bell’s), you had a positive serological test (ELISA and western blot), and you responded to antibiotics. This is very different from the pseudo-chronic lyme I was talking about in which the clinical case is atypical, the serology is negative, an there is no or only temporary response to antibiotics.

    What you have now is not chronic lyme (meaning a chronic persistent active infection) but chronic neurological sequella to a prior lyme infection. In other words, the infection is gone but the damage is done, and so there are lingering symptoms of the damage. Usually nerves will recover, but to a variable degree, and if the original infection was severe there can be permanent symptoms.

    I hope this clarifies things.

  8. dhmspectoron 14 Oct 2007 at 1:47 am

    Dr. Novella,

    Thanks for the clarification – I think my main point is that Lyme specifically is a much more subtle disease than is commonly acknowledged and is actually under-diagnosed because it’s so easily missed/mis-diagnosed.

    On the larger point of the existence of Chronic Lyme, as a software engineer who looks at almost every problem from a “systems viewpoint,” I think that doctors need to have better tools to track patient complaints/symptoms and have software that triggers/suggests things to look for (sort of an up-to-date version of the early expert system MYCIN).

    With the number of patients an average doctor sees and the long-delay between seemingly isolated events that could in fact be the outline of a bigger problem, there is no way any physician can keep track of all that information for every patient in their heads. Having better automatic analysis of patient records and diagnostic cues may help transform “Chronic Lyme” into other diagnoses for concrete diseases that can be actually treated…

    I think that if my GP had had such a system I might have been tested for Lyme a year earlier and not have had to go though such a painful experience. Similarly, for those with what they perceive to be “Chronic Lyme” might have had a different experience if their symptoms had been better tracked and correlated over time…

  9. NeuroLogica Blog » Morgellonson 22 Jan 2008 at 1:23 pm

    [...] disease itself, just a chronic undetectable form of the disease that requires chronic antibiotics. Here is a more thorough treatment of this [...]

  10. cesjron 18 Jun 2008 at 9:31 am

    Hi Steven,

    I am a big fan of the Skeptics Guide to the Universe. But I had a few questions about this blog posting.

    You state that: “Finally, there are antibiotics to which B. burgdorferi is sensitive, and if treated aggressively and long enough should eradicate the infection.”

    Why do you say “should”? As opposed to “will”? It seems that you are not confident that the scientific evidence establishes that antibiotics will always eradicate the infection.

    For example, I refer to the following:

    Bayer ME and Zhang L, Bayer MH (1996). “Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases”. Infection 24 (5): 347–353. doi:10.1007/BF01716077. PMID 8923044.

    Preac-Mursic V, Weber K, Pfister HW, et al (1989). “Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis”. Infection 17 (6): 355–359. doi:10.1007/BF01645543. PMID 2613324.

    Oksi J, Marjamaki M, Nikoskelainen J, and Viljanen MK (1999). “Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis”. Ann Med 31 (3): 225–232. doi:10.3109/07853899909115982. PMID 10442678.

    In light of these (and many other) published references to continued infection in antibiotically treated patients (proven by PCR and other objective means), how can you confidently assert the following in response to Dhmspector (or other patients experiencing continuing problems from a lyme infection):

    “What you have now is not chronic lyme (meaning a chronic persistent active infection) but chronic neurological sequella to a prior lyme infection. In other words, the infection is gone but the damage is done, and so there are lingering symptoms of the damage.”

    Clearly, this COULD be the case, for some patients or all patients hit with lyme that are experiencing continued symptoms. However, what scientific evidence establishes (beyond reasonable question) that this is in fact the case – for all patients experiencing continuing problems? Isn’t it equally plausible – given the scientific evidence of continued infection despite antibiotic treatment in some patients — that continued infection is causing the problem? Isn’t this a problem science hasn’t really figured out yet – so that bold pronouncements are unwarranted and potentially dangerous?

    One could cite the studies regarding lack of efficacy of long-term antibiotics for your position. However – and without getting into the merits of those studies — one cannot definitively tie lack of efficacy of antibiotic treatment to lack of presence of the organism. Simply because there could be other reasons for lack of efficacy of the treatment – including failure to completely eliminate the infection. This is rather starkly demonstrated by the above cited articles (and many others showing the same thing).

    Chronic lyme puts neurologists and ID doctors in a bind – it’s a tough thing to treat and diagnose because of the non-specific nature of the symptoms and the limitations of the testing (e.g., published articles have identified infection through PCR and other means in serologically negative patients). Also, the treatment has serious issues.

    But the science is the science – and I don’t see how there is a scientific basis for the conclusion that antibiotics will in fact always eliminate the infection – which I presume is why you use the fudge word “should” eliminate, as opposed to “will” eliminate.

  11. sesquapedalianon 29 Apr 2011 at 7:54 pm

    Whoa. Great article and comments, particularly the last one. I’m on the fence about chronic Lyme, although I was treated for it (after a positive Western Blot). I wonder if you’ve read the book “Everything You Need to Know About Lyme Disease and Other Tick-Borne Disorders”, by Karen Vanderhoof-Forschner. I read this while trying to figure out my own situation (I was menopausal and had a sore knee and what I like to think was temporary dementia, for which I wanted to blame something treatable like Lyme. I had also removed untold ticks from myself while tromping about on my land, where I discovered Lyme is endemic).

    Was Chronic Lyme an imaginary disorder with somewhat cult-like devotees who blamed it from an inability to balance one’s checkbook to failure to find lasting love? Or was it something that was difficult to either prove or disprove, whose sufferers and imagined-sufferers tended to the hysterical, thereby making physicians skeptical? Was this group being preyed on by a fringe-element bunch of practitioners, or undertreated because of conspiring pseudo-researchers and insurance companies who didn’t want to pay for PICC lines and months if not years of Rocephin and ever-more-exotic and expensive antibiotics?

    I’m sure the truth is somewhere in between, but I’ve seen what SEEM to be credible writings on the capacity of the Lyme spirochete to encapsulate and thereby resist Rocephin, the biggest-gun antibiotic usually used, to infiltrate the blood-brain barrier where many antibiotics don’t, so well, and to go dormant and resurface.

    Assuming these things are all true, I still think there’s a fair amount of hysteria about Lyme. I’m not convinced any of my “symptoms” (sore knee and forgetfulness) were caused by Lyme, or that my 30 days of IV Rocephin made any difference. I suspect every hiking dog in endemic areas has Lyme, yet the consensus among vets seems to be that dogs they rarely have symptoms. I’m guessing this is because dogs, with the notable exception of my chihuahua, are not prone to hysteria.

    I’d appreciate comments from you, Dr. Novella and cmsjr, on this. Thanks muchly.

  12. educatedguesson 04 Sep 2011 at 3:42 pm

    “It remains to be seen what effect, if any, this review published in a prestigious journal by recognized experts will have on the chronic Lyme subculture. I predict none. The evidence and arguments were all already there. Also, the chronic Lyme true believers are a self-selective group that have already proven resistant to logic and evidence.”
    Logic and evidence? Your blog is riddled with inaccuracies and grandiose self catered opinion. The slant you create is bloated with layers of serious corrupted thinking. Do you even consider published studies that differ from your obvious irrational stance? Obviously not. You are exactly the reason patients with Lyme or it’s co-infections can not get treatment. Pompous and insulting to the point of extremism. There is so much new evidence of persistent infection and yet you acknowledge none. Not a very ethical view Dr. Novella.
    Do people reading your blog know that you do not work for Yale? Your clinic rents the name for a fee. And yet strangely any doctor associated with Yale has the same illogical perception of what exactly ‘Lyme’ disease is.
    *”However, old habits die hard, particularly for the tradition-bound academicians at research institutions like Yale. Numerous patients have reported being told by Yale doctors that they didn’t have Lyme only to be diagnosed with it at a later date in its more severe chronic stages. Many Yale physicians are also conservative in prescribing the long-term intravenous antibiotic therapies which are increasingly thought to be the only option for people with recurring Lyme.”

    (basically blaming the condition on the patient and their fashionable hypochondriac Google driven search for relief) How is it possible the rest of the worlds researchers and scientists could be so wrong and you could be so right? You have no qualification or understanding of vector born diseases as you mainly utilize Botox as the cure all of your own practice. I really wish I could word my reply without resorting to name calling or bashing but science is science and you obviously have little understanding of what it means to be ethical in your approach of anything you disagree with.

  13. jpspickupon 14 Nov 2012 at 9:16 pm

    The best thing that could happen to a doctor that knows very little about lyme is to suffer from it him self and then write about it. otherwise everything you imagine is bla bla bla. you dont even mention lyme comes with many coinfections, and the testing that you rely on is completely inaccurate and can not be relied on when negative. the kind of aches and pains and brain symptoms normal healthy people suddenly come down with are not normal aging. you are the kind of doctor that lets people suffer needlessly.stop writing. you really have no personal experience and can never understand until you are sick your self.

  14. Steven Novellaon 15 Nov 2012 at 7:18 am

    educatedguess – you are wrong on every account. You are listening to mudslinging by quacks. I am a full time faculty member at Yale University in the department of Neurology. The Yale Medical Group is a group practice of Yale faculty. Also, I am a board certified neurologist, with subspecialty certification in Neuromuscular medicine. Botox therapy for neurological disorders is a very small part of my practice. You should be careful before you repeat libel.

    I am relaying the consensus of expert opinion. Your personal attacks do nothing to counter the facts. The only thing it accomplishes is to make you look foolish and contribute to the impression that the chronic Lyme subculture is not rational or evidence-based.

    JPS – the last statement applies to you as well. The evidence is what it is, whether or not I have personally suffered from Lyme disease.

  15. Dustpanon 24 Oct 2013 at 2:47 pm

    Also in response to the 6th response by # bachfiendon on 24 Aug 2010 at 5:32 pm,

    bachfiendon, you probably don’t have primary adrenal dysfunction but it is still possible that you could still of had secondary or tertiary adrenal dysfunction which would be hypo-pituitary or hypo-hypothalamus function. In other words dysfunction somewhere else within the Hypothathalmus-Pituitary-Adrenal (HPA) axis. If your not producing enough ACTH, then your adrenals aren’t going to produce cortisol because they aren’t getting the proper signal (ACTH) to do so. The end result without artificial stimulation of ACTH is very similar (a hypo cortisol state).

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