British billionaire's family stricken

General or non-medical topics with information and discussion related to Lyme disease and other tick-borne diseases.
Henry
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Re: British billionaire's family stricken

Post by Henry » Thu 17 Dec 2015 14:44

Please show me where the LD diagnostic algoritm that you mention is presented in the IDSA guidelines?

Henry
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Re: British billionaire's family stricken

Post by Henry » Thu 17 Dec 2015 19:19

dlf: The seronegative arm of the Klempner study was established in response to Lyme disease patient advocates who insisted that such a group be included. However, such patients were enrolled only if there was documentation of an EM rash in their medical history. Otherwise, they could not be enrolled.

My previous comments were made with respect to enrollment criteria for both arms of the study. The criteria were developed to ensure that those enrolled had a high probability of having PTLDS. That means that they had to have been correctly diagnosed (by CDC criteria) and then treated appropriately for Lyme disease as evidenced by their medical history. I think you would agree that if a lot of patients were enrolled who had symptoms very much like those of Lyme disease, but with no serological or clinical data to support the diagnosis of Lyme disease, they might have an unrelated medical condition that would not be responsive to antibiotic therapy; this would compromise the results of the study. Obviously, some patients were excluded from enrollment who had Lyme disease that was not documented adequately; however, those that were enrolled had a high probability of having had Lyme disease that presumably contributed to PTLSD. As you can see, it was difficult to find large numbers of these seronegative patients.

dlf
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Re: British billionaire's family stricken

Post by dlf » Thu 17 Dec 2015 21:55

Henry, you wrote:
It should be noted that in the Klempner studies, whether patients were seropositive or seronegative refers to their status at the time of enrollment , not at the time they originally were correctly diagnosed for Lyme disease by CDC criteria , 6 months or more before enrollment
( http://www.nejm.org/doi/pdf/10.1056/NEJM200107123450202 ). So, those studies had nothing to do with whether there is such a thing as seronegative Lyme disease per se.
Yes, I understand that the enrollment criteria had to ensure that the patients had been properly diagnosed and actually had PTLDS. I think the enrollment criteria did establish that these patients did have Lyme. The seronegative patients were properly diagnosed as having Lyme with appropriate physician documentation of an erythema migrans rash. We do agree on that. However, whether these patients ever had a positive serology test was not a factor in the inclusion or the exclusion criteria and they certainly did not test positive with serology at study entrance. The study did not report on whether those patients were ever tested or ever showed positive serology by CDC standards. Ergo, they had Lyme disease, but they were seronegative. Seronegative Lyme disease can and does occur as demonstrated by Klempner's study. Can we agree on this?

One of many problems with your argument and with your thinking that Lyme diagnosis must be predicated on positive serology relies on the physician not testing before antibodies fully develop and then testing multiple times until one test comes up positive. Usually they only test once or at most twice and then just tell the patient, "You don't have Lyme". Antibodies (particularly IgG) can take quite some time to develop even in immunocompetent patients and the immune response can be undulatory. Physicians would rarely even bother to test for immunocompetence. Many physicians miss the original rash (if the patient even sees or has one), or misdiagnose it as something else. So where does that leave the patient (like the patient profiled by Cheng) with a record of an erythema migrans who doesn't test positive until months and months later or ever?

There are lots of problems and limitations with the current Lyme serology. I suspect you may be the only IDSA supporter left who still believes that reactivity to CDC sanctioned North American two-tier serology should dictate whether a person can be diagnosed with Lyme or not. Well, maybe Ed McSweeney is also of that opinion, but the limitations seem to be recognized by many others.

Henry
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Re: British billionaire's family stricken

Post by Henry » Thu 17 Dec 2015 22:07

It's impossible to address the issues you raise adequately. A lot depends on when the infection is initiated, duration of exposure, and/or if symptoms are the result of a new or an old untreated (?) infection etc. Too much speculation, which I don't want to pursue. Faced with all the negative results and possibilities, it makes more sense to examine other causes rather than be fixated solely on Lyme disease as the one and only answer. There have been patients who have been treated by LLMDs for years, only to find that they have a thyroid problem or a vitamin B12 deficiency which, once identified and treated properly, were restored to good health. Perhaps the little girl in the wheel chair falls into that category?

dlf
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Re: British billionaire's family stricken

Post by dlf » Thu 17 Dec 2015 22:59

Henry,

By posting the ALDF Cheng-PDF, you were the one who opened up this speculation based on the issues that were included in the article. You are not that patient's physician and neither am I. It always makes sense to examine other causes rather than be fixated solely on Lyme disease as the one and only answer. It seems to me that in this little girl's case that had been done by the many physicians she did see, but perhaps not thoroughly enough, particularly by the hospital she was taken to when she became paralyzed. Neither of us are in a position to speculate on what actually took place. This is why the ALDF Cheng-PDF is objectionable. It assumes facts that are not in evidence. She may very well be suffering from Lyme disease.

But, you still didn't provide your answer as to whether we can agree that Klempner's treatment study demonstrated that patients with confirmed Lyme disease can in fact be seronegative. Did Klempner's study demonstrate this or not?

Henry
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Re: British billionaire's family stricken

Post by Henry » Thu 17 Dec 2015 23:57

Obviously, patients that are seronegative can have Lyme disease, providing they have an EM which -- as has been stated by the CDC-- is sufficiently diagnostic to justify recommended treatment. I thought I made that clear and it was a condition for enrollment in that arm of the Klempner study. Note that the EM rash appears early during infection, before sufficient amounts of antibody can be detected. So, the results you get depends on when you do the serology. Also, these patient were treated with antibiotics, but developed symptoms ascribed to CLD, 6 months or more later. Perhaps such treatment -- depending on when it is given-- may have prevented antibody formation from progressing to a higher level. I don't know. One would have to examine the clinical history of these patients and may still not get an answer. In any event, the investigators state that it was extremely difficult to find a lot of patients that fit this category. Finding enough patients for the seropositive arm of the study was not easy either.

Lyme disease is not such a mysterious thing and is no different that any other infectious disease. If one is infected for 4 or more weeks, the immune system -- unless the patient is immunocompetent is going to make antibodies specific for that infectious agent, with or without an EM rash. There is ample evidence to indicate that such antibodies can be detected by 2T testing -- certainly late after infection-- with a specificity of 100% and a sensitivity of 98-100%.

If the girl in the wheel chair had an EM, her health insurance company would not have denied payment. Most if not all health insurance companies accept the CDC's recommendation that an EM is sufficiently diagnostic for Lyme disease so that other serological tests would not be need to establish a diagnosis and justify recommended therapy. One must therefore assume that she was not only seronegative, but also did not have an EM. Tough to justify treating for Lyme disease under such conditions, let alone expecting a health insurance company to pay for it. Her symptoms must be due to other causes.
Last edited by Henry on Fri 18 Dec 2015 4:54, edited 2 times in total.

duncan
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Re: British billionaire's family stricken

Post by duncan » Fri 18 Dec 2015 1:31

Henry, are you saying patients can have Lyme and be seronegative, but in order for this phenomenon to occur they MUST have an EM (Period!!)?

There can be no instances of seronegative Lyme that did not manifest an EM?

Lorima
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Re: British billionaire's family stricken

Post by Lorima » Fri 18 Dec 2015 4:01

I seem to recall seeing the diagnostic flow chart, in Steere's chapter on LD in the dominant internal medicine text and reference book,
Harrison's Principles of Internal Medicine: Volumes 1 and 2, 18th Edition Hardcover – August 11, 2011
by Dan Longo (Author), Anthony Fauci (Author), & 4 more.

But it could have been Steere's chapter in an equally influential infectious disease textbook.

I'll check next time I'm at the library and get back to you.

Here are some web-accessible versions:

http://www.jci.org/articles/view/21681/ ... pdf/render
See figures 4 and 5
The emergence of Lyme disease.
Review article
Authors
Steere AC1, Coburn J, Glickstein L.
Author information
1Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. asteere@partners.org
Citation
J Clin Invest. 2004 Apr;113(8):1093-101.
PMID 15085185 [PubMed - indexed for MEDLINE] PMCID PMC38
http://www.aafp.org/afp/2005/0715/p297.html See figure 3.
Diagnosis of Lyme Disease

DANIEL L. DEPIETROPAOLO, M.D., Christiana Care Health Services, Wilmington, Delaware

JOHN H. POWERS, M.D., National Institutes of Health, Bethesda, Maryland

JAMES M. GILL, M.D., M.P.H., and ANDREW J. FOY, Christiana Care Health Services, Wilmington, Delaware;

Am Fam Physician. 2005 Jul 15;72(2):297-304.
I will edit my comment from "IDSA's oversimplified diagnostic algorithm" to "Steere's oversimplified diagnostic algorithm."

As you know, diagnostic recommendations have not changed since 2004.
"I have to understand the world, you see."
Richard Feynman

Henry
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Re: British billionaire's family stricken

Post by Henry » Fri 18 Dec 2015 4:25

Lorima: A close examination of the IDSA guidelines reveals that they do not address the issue of diagnosis. To save time, go to the CDC's website where you will find the algorithm you are searching for. It wasn't designed by Steere, although he may have referenced it in several of his publications.

The criteria for 2T testing was established by the CDC and approved by the FDA. Complete details may be found on their website. The IDSA was not involved in that process; their guideline address the treatment of those who have been properly diagnosed for Lyme disease. So if you have any concerns about 2T testing, go to the CDC. They have lots of information on all that.

Incidentally, there is an excellent paper that has just been published on Lyme disease serology by M.E. Schriefer at the CDC (Clin Lab Med 35: (2015) 797-814. It gives a complete history and goes into great detail on the development of criteria for Western blots , as well as issues related to sensitivity and specificity for tests conducted during various stages of Lyme disease (early to late).

Henry
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Joined: Thu 10 Nov 2011 18:49

Re: British billionaire's family stricken

Post by Henry » Fri 18 Dec 2015 4:55

Duncan: See revised previous comments on that issue.

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