Wednesday, July 15, 2009

Science-based medicine conference, part 5: chronic lyme disease

This is part five of my summary of the Science-Based Medicine conference at TAM7, which will be followed by a summary of TAM7 itself. Part one, Dr. Steven Novella's introduction, is here. Part two, Dr. David Gorski on cancer quackery, is here. Part three, Dr. Harriet Hall on chiropractic, is here. Part four, Dr. Kimball Atwood on evidence-based medicine and homeopathy, is here.

The fifth session speaker was Dr. Mark Crislip, infectious disease specialist and host of the Quackcast podcast, on "Lyme from the IDSA to the ILADS to the ABA."

Like several of the other speakers, Dr. Crislip began with a disclosure of potential conflicts of interest, saying that he had "barely any" and "[hasn't] spoken to a drug rep in 25 years."

He started his talk with a description of Lyme disease. It's caused by a spirochete related to syphilis, that comes in three varieties, European, Asian, and North American. The latter is Borellia burgdorferi, a nasty little organism that lives in ticks, primarily deer ticks. It's transmitted via a tick bite, requiring 36 hours of attachment for transmission, and has grown in prevalence in the northeastern United States with the growth of the deer population. In the northeastern U.S., most ticks have Lyme, while in the northwestern U.S., only 1.3% of ticks have Lyme, because those ticks feed on the blood of a fence-sitting lizard that contains something that kills the spirochetes. (Here, Dr. Crislip joked that despite the presence of numerous fence-sitting lizards in Washington, D.C., the effect doesn't work there.)

North American Lyme disease goes through three stages:
  1. skin rash, arthritis
  2. spreads to whole body, causes meningitis
  3. results in encephalomyelitis and neurological symptoms
There are drugs that work well to treat the disease at all three stages.

However, there are "also people who think they have Lyme but don't," or "post-Lyme disease."

Two Camps
Dr. Crislip identified two groups that have radically different views about Lyme disease:

1. The Infectious Diseases Society of America (IDSA).
2. The International Lme and Associated Diseases Society (ILADS)

The latter says that Lyme is common, hard to diagnose, and "requires infinite antibiotic treatment." The former says nearly the opposite.

The New England Journal of Medicine published a critical appraisal of "chronic Lyme disease" which put the sufferers into four categories:

1. Symptoms of unknown cause, no evidence of B. bergdorferi.
2. Well-defined illness unrelated to B. Bergdorferi (e.g., ringworm).
3. No history of Lyme disease, but blood contains B. Bergdorferi antibodies.
4. Post-Lyme disease syndrome, chronic illness.

The study performed controlled trials of those in category four, and concluded that there is no evidence of B. Bergdorferi persisting beyond treatment, the name "chronic Lyme disease" is a misnomer, and there is no justification for continued antibiotic treatment of such persons.

Dr. Crislip then stated that the two camps present a false dichotomy, but that the truth is closer to the IDSA position. He asked, "is there asymptomatic Lyme?", and answered "yes." 7% of test subjects have asymptomatic seroconversion (show B. Bergdorferi antibodies) in vaccine trial placebo groups. He asked, "can [Lyme be] persistent due to antibiotic resistance?", and answered that there is no good data of that.

He pointed out that Borellia can exist in three forms, the spirochete, a cyst, and an L-shaped form with no cell wall. The cysts appear when the organism is stressed, but isn't found in humans (and is supported in fewer than 25 references in PubMed) and the L-shaped form can be made in the lab but doesn't survive in humans.

Diagnostic Testing
Dr. Crislip said that the standard test for Lyme disease is a two-step process, an ELISA test confirmed with a Western Blot (the same process used for testing for HIV). With classic Lyme disease, this is a very reliable method. It can also be tested with PCR and with antigen assays, and "there is genotypic variation in Lyme that could potentially make the two-step test less sensitive."

There are also labs which perform their own unvalidated tests, such as a lab in Texas that he says "almost always yield[s] positive results." These labs with unvalidated diagnostic tests have caused the CDC and FDA to issue warnings about non-valid Lyme tests.

Dr. Crislip posted a list of alleged symptoms of chronic Lyme disease, which was a very long list including "unexplained hair loss" and "feeling as if you are losing your mind," along with another list of alleged symptoms of chronic candida, and noted that they were quite similar. Using such lists, virtually any symptom is an indicator of these alleged chronic conditions.

The ILADS guidelines go even further, and say such things as:
  • The labs are all unreliable, so treat for Lyme even if the test is negative.
  • The primary symptom is that the patient thinks they have the condition.
  • Physical findings are nonspecific and often normal.
  • If the Western blot result is ambiguous, treat it as positive (the opposite of what you do with HIV).
  • A comparison to tuberculosis and leprosy provides justification for long-term antibiotic treatment (even though those diseases are biologically dissimilar to Lyme).
In short, the ILADS guidelines provide a nonfalsifiable definition of Lyme disease.

The best trials in the NEJM treated Lyme disease patients with a month of cipro (and?) doxycycline. The "chronic Lyme disease" advocates say that the immune system is damaged with antibiotic use, and then Lyme disease increases as the immune response declines--based on no data.

If you don't have the data, sue
The state of Connecticut passed a bill "giving doctors immunity for giving infinite supplies of antibiotics" to patients purportedly suffering from "chronic Lyme disease." Since the IDSA guidelines are against long-term antibiotic use, the Connecticut Attorney General sued the IDSA. They couldn't afford $250,000 in legal expenses, so they settled the case.

Dr. Crislip concluded by pointing out that the cause of this unsubstantiated syndrome will be promoted by a new film coming out, called "Under Our Skin," which has the tag line "There's no medicine for someone like you." Crislip noted that of the two doctors in the film promoting this illness, one lost his license for diagnosing Lyme disease over the telephone.

(Part six of my conference summary, on online health and social media, and the final Q&A panel session, is here.)


Nickname said...

Wow, a lot of slanted opinion in this article. It doesn't take a genius to figure out that when the medical establishment is publishing obviously propagandist articles like "A Critical Appraisal of Chronic Lyme Disease" by the same authors that came up with the diagnosis and treatment guidelines, that something has gone horribly wrong in medicine. Check out the conflicts of interest published along with the article:

Dr. Feder reports receiving lecture fees from Merck and serving as an expert witness in medical-malpractice cases related to Lyme disease. Dr. Johnson reports holding patents on diagnostic antigens for Lyme disease. Dr. O'Connell reports serving as an expert witness related to Lyme disease issues in civil and criminal cases in England. Dr. Shapiro reports serving as an expert witness in medical-malpractice cases related to Lyme disease, reviewing claims of disability related to Lyme disease for Metropolitan Life Insurance Company, and receiving speaker's fees from Merck and Sanofi-Aventis. Dr. Steere reports receiving a research grant from Viramed and fees from Novartis. Dr. Wormser reports receiving research grants related to Lyme disease from Immunetics, Bio-Rad, and Biopeptides and education grants from Merck and AstraZeneca to New York Medical College for visiting lecturers for infectious-disease grand rounds, being part owner of Diaspex (a company that is now inactive with no products or services), owning equity in Abbott, serving as an expert witness in a medical-malpractice case, and being retained in other medical-malpractice cases involving Lyme disease. He may become a consultant to Biopeptides. No other potential conflict of interest relevant to this article was reported.

I think I will have to go with Upton Sinclair on this one. "It is difficult to get a man to understand something when his salary depends upon his not understanding it."

Lippard said...

a_riot: You say there is "a lot of slanted opinion in this article," but you didn't identify any. What I wrote is a summary of Dr. Crislip's presentation. You'll note that although he cited the NEJM article, he "stated that the two camps present a false dichotomy."

I agree with you that if someone has financial interests in holding and arguing for a particular position, that is a reason for skepticism--and is the reason for academic disclosure standards on such article publications.

I also think that there is good evidence that some diseases of recent vintage without obvious causes do have real causes beyond the psychological, such as chronic fatigue syndrome, which many doctors have been skeptical about but now has been correlated with the XMRV retrovirus (which may not be the actual cause). New developments in the emerging field of "personalized medicine" will probably be revolutionary in identifying new diseases and subtypes of diseases.

That said, however, there are obviously still significant psychological and sociological factors that can lead to erroneous reports, and the main upshot of Dr. Crislip's talk seems to be that there is little or no evidence that what is called "chronic lyme disease" is related to the spirochete that causes lyme disease, and you've presented no evidence to the contrary.

Nickname said...

"the main upshot of Dr. Crislip's talk seems to be that there is little or no evidence that what is called "chronic lyme disease" is related to the spirochete that causes lyme disease, and you've presented no evidence to the contrary."

There are plenty of peer reviewed studies showing the persistence of borrelia past the standard 2-4 weeks of treatment both in animals and humans, and I am sure whoever has the desire can easily find them. Ask any veterinarian, as they correctly treat lyme disease as a relapsing disease that is very dangerous. Animals are treated more carefully than humans when it comes to this illness. The 'there is no scientific evidence that...' ruse is often used to try and discredit anyone not in the medical establishment, but absence of evidence is not evidence of absence. There are no double-blind placebo controlled studies showing that banging your head against the wall can cause concussion. So I guess you wouldn't recommend I stop?

Lippard said...

You seem to be asserting that chronic Lyme disease is caused by the persistence of borrelia beyond original treatment, but the best available evidence is that diagnoses of chronic Lyme disease are being made in the absence of supporting evidence of that, similar to past erroneous diagnoses of "tertiary syphilis." The recommended treatment also seems to be long-term use of antibiotics, which the available evidence also suggests is not effective.

We don't need double-blind placebo controlled trials to learn *anything*, but it certainly seems to be the best method for determining the efficacy of medical treatments of chronic conditions. Your example of concussion isn't analogous.


NeuroLogica Blog, "The NEJM Takes on Lyme Quackery"

Science-Based Medicine Blog, "Lyme disease--who is credible?"

Science-Based Medicine Blog, "Define the disease first"