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Define the disease first

My first post on this blog addressed the problem of what I have called “fake diseases” (a problem which needs a more neutral moniker). As I wrote at the time, people suffering from vague ailments are often twice victimized: the medical establishment cannot satisfy them, and quacks prey on them. There’s a certain sense of satisfaction and validation to having your symptoms clearly labeled. While it isn’t a good thing to have heart disease, no one tells you you’re not sick. Not so with people with more vague and protean symptoms. It’s human nature to want answers, to try to understand patterns, and when we, as physicians, cannot help someone understand their symptoms, they’re going to reach out to others for answers.

The Lyme disease community is like that. The internet has helped them to form communities and to share information. This whole idea of “chronic Lyme disease” (CLD) has become a way for people who don’t feel they have a medical home to come together. I understand that impulse. Any human being should be able to understand it.

But the other side of me, the analytic side, has a problem with it. No, not a problem with people supporting each other, but if you read these websites, message boards, etc., you can see a certain commonality—people aren’t getting any better. They are still suffering. Much of that suffering is blamed on a heartless medical community, and when they find a “Lyme literate” doctor, there is a huge sense of relief. But the symptoms often continue.

The very idea of CLD is not implausible (as opposed to Morgellons and other such fake diseases). Other spirochetes give us models for diseases with extended, multi-system effects, syphilis being the most studied. One of the key concepts in science-based medicine is plausibility, because, as Dr. Harriet Hall puts it, no matter how much you study the characteristics of the tooth fairly, you still haven’t proven her existence. But CLD certainly has a plausibility to it, and if an idea is plausible, then it is certainly worth studying and gathering evidence.

The evidence so far has been fairly clear: lyme disease is a common, tick-borne illness that can cause a host of symptoms days to weeks to months after initial infection. These clinical syndromes, such as Lyme arthritis, neuroborreliosis, and carditis are fairly well described. Part of the problem is epistemology and ontology—what is a disease? We have a couple of ways of going about defining diseases. One pathophysiological; if we can see clearly define a disruption of normal function or anatomy, there is a satisfying clarity. Another is genetic; if we can trace pathophysiologic changes to a specific genetic change, Bingo! Of course, genes are rather complicated, and the relationship between genotype and phenotype can sometimes be frustratingly variable. But no one said science would be easy.

The least satisfying way of defining a disease is syndromic. Humans are pattern monkeys, which is both a good and a bad thing. The earliest medical texts were descriptive, and defined illnesses by their outward manifestations, the inner workings being inaccessible to the ancients. We still are forced to resort to description from time to time in medicine. For example, in the 80′s a new disease emerged which didn’t appear to be any single disease but a grouping of different diseases and symptoms with some commonalities. We called this grouping “Acquired Immune Deficiency Syndrome” to acknowledge the fact that all the patients had immune dysfunction and all appeared to have “acquired” it rather than having been born with it. It was called a “syndrome” rather than a disease because it was more of a grouping of illnesses and the unifying pathology wasn’t yet understood. (Now, of course, HIV disease is one of the best understood illnesses in human history.)

Ultimately, the goal of defining a syndrome is to look for the disease or diseases that may underlie the symptoms. We realize that when we define a syndrome we may improperly include and exclude patients from our net, but we try to come up with rational definitions so that we may find the cause. “Syndrome” is more of a tool than an explanation but it can be a very useful tool.

Where this breaks down pretty spectacularly is when we define a syndrome poorly, or make too many assumptions. This is one of the fundamental problems with chronic Lyme disease. Let’s look at this from both ends.

One way of defining a disease is to create criteria and then look for “victims”. We (think) we know what Lyme disease is: in the U.S. it is an infection with a spirochete known as Borrelia burdorferi sensu strictu. This infection can cause a number of symptoms, some of which are a direct result of the infection and some of which are immunologic (which hardly makes it unique). We can define this illness by pathophysiology, anatomy, and microbiology. This inherently limits who we can call a Lyme disease patient. For example, if someone comes to me with knee pain, but has not been to a Lyme-endemic area, has no other signs of Lyme disease, and tests negative for Lyme disease antibodies, we will not label this patient as having Lyme disease. But these lines are, unavoidably, going to blur in some patients. Despite our knowledge of medical science, there is sometimes a small bit of arbitrariness in designating someone as having a disease. But that arbitrariness is smaller the better we understand a disease. Still, when we designate someone as having a disease based on them meeting criteria we set, we will accidentally leave some people out.

The other way to understand illness is to gather in victims and try to shove them into a disease category. If we see a pattern, such as people suffering from similar symptoms and no known cause, and we have a disease that might explain their symptoms, it can be tempting to shove these people into that disease category. This approach will have the opposite type of error to the first—we will accidentally diagnose people with the disease who do not in fact have it.

We try to minimize both of these types of errors, but since we are dealing with real people, these errors can lead to real suffering. When it comes to chronic Lyme disease, self-defined victims feel we are making the first type of error, and most medical scientists feel we are making the second. Are these irreconcilable differences?

Yes, and no. There are ways we can help reconcile these differences, and ways in which we can drive people further apart. The problem with “chronic Lyme disease” and Morgellons syndrome is what Dr. Harriet Hall calls “tooth fairly science”. Many folks have stopped by the comment section at my other blog lately to explain why this or that theory correctly explains various symptoms and outcomes in CLD, but what they haven’t done is first shown that the disease in fact exists. This leads to infinite recursions of our second type of error. If you have not yet proved the existence of CLD, if you have no clear diagnostic criteria, then anyone can have it, and definitions without boundaries are useless. If the CLD folks want to be taken seriously by the rest of the medical community, they must drop their conspiracy theories and do real, difficult science. More important, they must be willing to accept the answers that the science gives them.

You see, in medicine, the stakes are very real. My job would be much easier if I had the hubris to simply declare someone to be ill or well, to have disease A or B, to lay on hands and heal. But I can’t do that. My MD didn’t come with superpowers (and if it did, I still would have chosen flying; I mean, c’mon…). But what we have to work with is still very powerful. We have a way of approaching human health and disease that is unmatched in human history. While our ancestors struggled to understand disease, they bounced from one bad hypothesis to the next, from humors to spirits to bad air. Over the last century, we have developed (and continue to refine) our current science-based approach to medicine.

The most important fact in the grey areas of medicine is that real people suffer. Part of this suffering is the feeling of being ignored, or worse, dismissed. No matter what we as doctors do, some people will always feel this way. But currently, many more do than need to. The sense of victimization felt by some of the CLD folks has become part of their identity. We need to help avoid making people feel victimized. When they do, they will run into the arms of any charlatan who gives them an answer, and be further victimized. This reconciliation is going to require a great deal of patience, but it will happen, with time. As much as people might not believe it, science always brings the closest approximation of the truth—but sometimes it takes time.

Posted in: Science and Medicine

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17 thoughts on “Define the disease first

  1. Karl Withakay says:

    “The other way to understand illness is to gather in victims and try to shove them into a disease category. If we see a pattern, such as people suffering from similar symptoms and no known cause, and we have a disease that might explain their symptoms, it can be tempting to shove these people into that disease category. This approach will have the opposite type of error to the first—we will accidentally diagnose people with the disease who do not in fact have it.”

    The other obvious problem with this approach is that it tends to assume that there is a single disease common to all diagnosed sufferers of a defined syndrome- Chronic Lyme Disease, Gulf War Disease, etc, when the “syndrome” may actually be multiple overlapping and unrelated conditions with different root causes.

    As has been explained before both here and elsewhere, humans are pattern seeking beings, and we are often able to find meaningful patterns even when none actually exist.

    Diagnoses like CLD have a kind of black hole effect, where anything that strays inside their event horizon gets sucked in and attributed to CLD.

  2. sowellfan says:

    Does anyone have good skeptical links that talk more in-depth about the flawed ideas behind CLD? The Diane Rehm show had a segment about CLD a couple weeks back, and they had a doctor arguing the factual medical side, but he was opposed by one doctor and one journalist presenting the side that believes strongly in CLD. The doctor who was pushing CLD talked about various lab tests that supposedly proved the existence of this disease, but I haven’t really been able to find anything that addresses these various arguments one by one.

  3. I really need to explain a few things.before I begin. I have Morgellons. I am very sick. Some days are better than others. My energy level runs down faster than a dollar store battery. In the beginning (2001), I was determined to find what was making me sick. Then, I planned to march into the Drs’ offices (of the ones that had failed me ) and confront them with what I had uncovered. All I wanted was an apology.( as well as proper medical care). Of course, this did not happen. Little did I (or any of us) realize how complicated this condition was. As an RN of over 32 yrs, I dedicated most of my life to medicine. I still cannot understand how the best medical minds in the greatest country ever could not figure out what was literally stealing my life away. I apologize for the emotional scene. If any one of you reading this had experienced what Morgellons patients have gone through, only then, could you possibly comprehend the paroxysmal commitment to learning the scientific & medical cause and treatment for Morgellons that \we have. I am sure a few will post snide remarks and cutting analytical comebacks. Since my energies are limited, I may not be able to respond. Please know that I appreciate you took the time to read what I have written. At the very least you had to think about us “Morgies” for one minute. And, that’s a start to opening a mind.
    This article calling Morgellons a fake seems to be getting around the Internet at a rapid pace. In some ways, this can be viewed as positive. More people are learning about this serious condition as the debates and discussions continue. For those of you that are just arriving, here is the link to where it seems to have started. I do not feel it is necessary to repost everything here. http://scienceblogs.com/whitecoatunderground/2009/05/saturday_morning_reflections.php

    Morgellons is a very real and life altering disease. The CDC stated, “…Morgellons is an unexplained and debilitating condition that has emerged as a public health concern. … The on going research is certainly science based and peer reviewed. This is one reason that it is taking so long. At present more than 20,000 households are registered with Oklahoma State University Center for Health Sciences. The university generously is hosting the site for The Center for the Investigation of Morgellons Disease. The volunteer Director is Dr. Randy Wymore, PhD. (Here is a brief bit of information about him: “Randy S. Wymore holds PhDs in Physiology and Biophysics and Pharmacology; … has co-authored seventeen articles published in peer-reviewed scientific journals ;… was involved in cancer & heart disease research before taking on Morgellons”. Dr. Wymore came into the Morgellons arena as a skeptic. After viewing some actual lab specimens, he was soon convinced as to the reality of this condition. Since 2005, he has struggled through investigating Morgellons where answers only produced more questions and puzzling dead ends.
    Despite his full responsibilities as a Professor in the OSU Medical School & family obligations, Dr. Wymore volunteers his time to research Morgellons Disease. We are fortunate to have him. Any other qualified scientists that would like to join his team are encouraged and welcomed. Please contact Dr. Wymore at OSU via email which is on his website. Here is the link to OSU’s website for further details about on going research: http://healthsciences.okstate.edu/morgellons/

    Before citing Morgellons as a “fake disease”, at least consider the known facts. Thousands of patients suffering with this horrendous and life altering illness deserve compassion, empathic understanding and proper medical management. We have come a long way from the non-believing doctors/medical practitioners encountered in previous years. Presently, many more medical professionals are opening their eyes, minds, & offices to Morgellons patients. After taking time to read the facts for themselves, these caring individuals have realized the truth. For anyone that is interested in further information, I have included links:

    http://healthsciences.okstate.edu/morgellons/
    http://thenmo.org/)
    http://www.cdc.gov/unexplaineddermopathy
    http://www.clongen.com/morgellons_disease.php
    http://www.morgellons.org/

    Gwen Simmons, RN

  4. daedalus2u says:

    Gwen, I have posted about Morgellons.

    http://daedalus2u.blogspot.com/2008/02/morgellons-disease-hallucinatory.html

    I think the symptoms are real, just not caused by a parasite.

  5. Mojo says:

    My energy level runs down faster than a dollar store battery.

    By this, do you mean to say that you get tired quickly?

  6. Scott says:

    Gwen,

    Peter’s not arguing that there aren’t real and troubling symptoms that have been labelled as “Morgellon’s.” His argument is that there is no good evidence that there’s actually a single problem which is leading to those symptoms in all people so labelled, or that such symptoms result from a parasite.

    And until there IS such good evidence, assuming that it is known what’s going on is highly counterproductive, as it diverts attention and resources from figuring out what the real story is. So you’re doing not only yourself, but everyone with similar symptoms, a GRAVE disservice.

  7. ticker says:

    It’s worth mentioning that there are also diseases which are too fuzzy at first.

    In my family, a condition called Ankylosing Spondylitis is uncommon (about 1/15 get it) and while we’re rather familiar with it, doctors aren’t, and besides, the initial symptoms are too ambiguous or diverse.

    It’s not a life-threatening condition in that it might kill you, but it is severely inconvenient because it makes it impossible (or very hard) to work for a living and maintain your own home properly.

    This inconvenience starts long before a positive diagnosis is possible. While we know what we’re dealing with, the best a doctor can say is that it’s unclear whether it really is AS or not.

    The “gold standard” (there isn’t really one) for diagnosis is a combination of detecting an amino acid which occurs in far more than the number of actual AS patients, and there’s also AS patients who don’t have it, and scans of the skeleton for specific damage which can fail to be visible for over a decade of suffering.

    This all is highly vexing, but we’re aware it’s simply not possible to unambiguously demonstrate AS when it hasn’t progressed beyond a certain point. I wonder how AS patients from families where it is extremely rare deal with this gap between onset of serious, debilitating symptoms and actual diagnosis by a competent doctor.

    It must be awfully tempting to run to the frauds who promise you’ll be free of all your symptoms, especially when doctors will for years do nothing for you.

    It’s not malice, it’s simply that no doctor worth their degree will commence treatment before establishing a reliable diagnosis. Treating someone for the wrong illness might as well worsen the one they really have, which for someone with AS is in fact rather easy to do. I’ve heard rather terrifying stories about what happened to my ancestors before this disease was known.

    My point with all this is, just how many people with an initially ambiguous or even invisible illness will end up in some of these “black hole” categories for years? And worse, they will be delaying an already rather late diagnosis even further as they seek to justify and advocate for a disease which simply isn’t their problem, or might not even exist.

    I suppose it’s simply hard to accept that sometimes the honest truth about your own personal health is “too soon to tell”. Not to mention that you generally don’t get any form of disability benefits for that, while still not being able to work for a living.

  8. Prometheus says:

    Gwen,

    Dr. Wymore has been studying Morgellons for four years and hasn’t published a single paper on it. In fact, the last publication I can find for him was in 2005, on integrins.

    I would be very interested to see what a real scientific analysis would make of the “blue, red or black” fibers “Morgellons Disease” sufferers pull from their skin. I would also be interested in the results of any DNA testing of these fibers. I wonder if the “Morgellons Disease” groups would be as accepting of the results if they fail to show what they expect.

    This is not to say that the symptoms experienced by people who identify themselves as having “Morgellons Disease” aren’t real – they may be very real, indeed. However, it remains to be seen if all – or even most – of the people who identify themselves as having “Morgellons Disease” actually have the same disorder.

    Prometheus

  9. medstudent6973 says:

    Gwen, you clearly didn’t read the his article. If you did, you clearly didn’t understand it. In fact, you never even once mentioned his extremely well written and informative article. It looks as if you’ve just copied and pasted a propaganda piece on morgellon’s.

    You completely missed the big points.

    1. Nobody is denying that your symptoms are real.
    2. At this point, it should be called “Morgellon’s Syndrome” because it’s a series of symptoms of unknown cause. When you or somebody else figures out what is causing the syndrome, then you can call it Morgellon’s Disease.

    Your post suggests multiple times that you ALREADY KNOW THE ANSWER and the mean, stubborn doctor’s won’t listen. While you didn’t directly say it, the context of your sentences demonstrates that you haven’t an ounce of healthy skepticism. You need to understand that there is a great deal of evidence that suggests Morgellon’s is relabeled “delusional parasitosis”. If you deny that even some of this evidence exists, then it is you who is being stubborn.

    While more evidence is being gathered, please stop referring to it as Morgellon’s “disease”. Take solace in the fact that we humans have not discovered and named every ailment that plagues the human body. By simple probability, it’s almost certain that there are some obscure connective-tissue diseases that we have yet to realize. Nobody is doubting that you may be suffering from real symptoms, perhaps from an unknown disease. If you want to sound intelligent and have people take you seriously, stick with this argument. The moment you bring up the “alien fibers”… you won’t be taken seriously by any real doctor or scientist.

  10. tmac57 says:

    I am struck by the similarities of the symptoms of CLD, Morgellon’s ,Chronic fatigue syndrome, and Fibromyalgia.

  11. daedalus2u says:

    tmac57, I think that one of the reasons that those disorders are so similar is because they all have the final common pathway of low NO (including ankylosing spondylitis). Low NO increases the “gain” of the immune system and that increased gain is what causes the chronic inflammation that characterizes most of these disorders (and disorders that are associated with them). Acute low NO (from the respiratory burst) increases the gain and produces a robust turn on. Chronic inflammation decreases NO also, and can lead to a permanent state of low NO. You want inflammation to increase the “gain” on the immune system, so you get positive feedback and a robust “turn-on” when you need it, especially locally before a small infection gets big. Without enough basal NO to reduce the gain, you end up with too much gain, and too much “feedback” (as when you put a microphone next to a speaker).

    The immune system (like virtually all evolved systems) operates with automatic gain control. That automatic gain control is modulated up and down via what is known as stochastic resonance (for the most part). The gain creeps up until something gets activated and then it creeps down. The ups and downs of normal immune system activation keep everything in balance. It isn’t a static balance, it is a dynamic balance.

    People don’t appreciate that the most complex physiological state is the state at rest where all of the up and down pathways are exactly in balance. As you move away from the “at rest balance point”, some pathways get turned off and stay off. That makes the physiological state away from the “at rest” state more simple because less is going on.

    Low NO reduces mitochondrial biogenesis so you end up with fewer mitochondria generating the same ATP by working at a higher membrane potential. That is ok at rest, but there is no excess mitochondrial capacity to generate more ATP if you increase your metabolic activity so you fatigue easily. That is why chronic fatigue is a common symptom to all of these disorders, and comes from the same mechanism as occurs during normal deconditioning, not enough mitochondria biogenesis.

    TNF-alpha causes production of superoxide and reduces local NO levels. Block the action of TNF-alpha on its receptors with Etanercept and you improve ankylosing spondylitis (I think by increasing NO levels). I think this is the mechanism by which Etanercept causes a prompt improvement in Alzheimer’s disease, due to reduction in superoxide and prompt increases in NO.

    What is quite interesting is that Etanercept (a TNF-alpha blocker) and Infliximab (a TNF-alpha monoclonal antibody) have similar effects on ankylosing spondylitis yet quite different effects on Crohn’s disease (for some individuals).

  12. DLC says:

    On the other hand, sorry to sound rude about it, but there are many out there who would fall into the “worried well” category.
    People who interpret otherwise normal aches and pains as some sort of illness. “Something has to be wrong” he says, because his ‘energy level’ isn’t right or he has ‘brain fog’.
    then there are some people seem to select a label for their illness and then doctor-shop until they get one who agrees with them.
    I’m reminded of the Seinfeld episode wherein George is told he has lupus. He does not want to have lupus, so he insists it must be cancer.

  13. The Blind Watchmaker says:

    Unfortunately, many people suffer from (as Dr. Novella describes it) “symptoms of living”. People come to the doctor with a list of complaints. We must listen to the complaints, weigh them with respect to known medical problems and evaluate them when appropriate. Most people just want to know if they are ok or not. When their symptoms are benign “symptoms of living”, most are happy with that. The doctor must ensure the patient that he/she is available to them if things do not go as planned or other problems develop. The patient and doctor must act as a team. Patients do not (and should not) want to get the idea that a doctor is shrugging off their complaints.

    Rarely, there are individuals that cling to (sometimes implausible) ideas of illness when there clearly isn’t any illness to be found. They point out the anecdotes of unfortunate patients that had missed diagnoses. As doctors, we must be sympathetic to these patients as well. Provided that the doctor has done the appropriate investigations, it is ok to acknowledge the symptoms and state that a “disease” has not been found. Referrals to tertiary care centers can be very helpful. Occasionally, serious diagnoses surface after evaluation by specialized experts. More often though, if the work-up remains negative after due diligence, reassurance and validation is what people are looking for.

  14. tmac57 says:

    The Blind Watchmaker- That makes a lot of sense to me, but not being a physician, I would never openly be skeptical of someone’s ‘disease’ because after all, what do I know about it.
    It does seem like exercise is often beneficial for people with these constellations of symptoms, but I bet it is hard to get them moving, since they are already in so much discomfort. I have suffered with chronic back pain most of my life, and have found that getting moving (exercise) is usually the best remedy, but boy is it initially difficult to work through that pain.

  15. yeahsurewhatever says:

    “One way of defining a disease is to create criteria and then look for “victims”. We (think) we know what Lyme disease is: in the U.S. it is an infection with a spirochete known as Borrelia burdorferi sensu strictu.”

    Your illiteracy of Latin is showing. ‘Sensu strictu’ simply means ‘in a strict sense’ and is not part of the name of B. burgdorferi, which you also misspelled. It was named after medical entomologist William Burgdorfer, PhD, the first man to describe its role in human illness.

    http://lymerick.net/1999-Burgdorfer-keynote.pdf

  16. Prometheus says:

    The use of “sensu stricto” in taxonomy simply means that there are more than one way of defining the species (or genus or…) and that the organism in question is the one described by the narrowest definition. The opposite would be “sensu lato

    Contrary to what “yeahsurewhatever” has said, the use of “sensu stricto” is common when Borrelia burgdorferi is discussed, as there are both narrow and broad definitions of that species.

    Dr. Lipson’s typographical errors are – of course – to be deplored by all who are inerrant in their typing.

    Prometheus

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