Re: a few things

a_weisman_at_yahoo.com
Date: 02/20/05 

Date: 20 Feb 2005 08:20:59 -0800

a_weisman@yahoo.com wrote:

Picking up where I left off or thereabouts:

> Clinical Manifestations
>
> In untreated patients, Lyme disease usually occurs in stages, with
> different manifestations at each stage.7 In at least 80% of patients,
> the infection begins with a slowly expanding skin lesion, erythema
> migrans (stage 1),8-9 which occurs at the site of the tick bite. As
the
> lesion expands, it often develops partial central clearing with a
> redder outer border. The skin lesion is frequently accompanied by
> nonspecific systemic symptoms, such as malaise and fatigue, headache,
> arthralgias, myalgias, fever, or regional lymphadenopathy.
>
> Apparently, Mr C did not have this characteristic skin lesion of Lyme
> disease. Instead, his illness presented with facial palsy in August
> 1992, which was treated with prednisone. The palsy resolved in about
3
> weeks. Within several weeks after inoculation by the tick, B
> burgdorferi often spreads hematogenously (stage 2). During this
period,
> acute neuroborreliosis develops in about 15% of untreated patients,7
> often in July or August. Possible manifestations include lymphocytic
> meningitis with episodic headache and neck stiffness, subtle
> encephalitis with cognitive difficulty, cranial neuropathy
> (particularly unilateral or bilateral facial palsy), motor or sensory
> radiculoneuritis, mononeuritis multiplex, cerebellar ataxia, or
> myelitis.10-11
>
> Occasionally, facial palsy may be the presenting manifestation of the
> illness. In a Lyme disease vaccine trial in which an attempt was made
> to identify all cases of the infection that occurred in the study
> population, 1 of 269 patients (0.4%) presented with facial palsy.12
In
> an animal model of neuroborreliosis, it has been demonstrated that B
> burgdorferi first infects the meninges and may spread to connective
> tissue surrounding the facial nerve.13 However, even if patients are
> treated only with prednisone, a common therapy for facial palsy,
acute
> neurologic abnormalities usually resolve within weeks or months.14
>
> After this point, Mr C's illness begins to diverge from what would be
> expected in the later stages of untreated Lyme disease. Within months
> after acute neuroborreliosis, untreated patients usually develop
> intermittent attacks or chronic oligoarticular arthritis (stage 3),15
> which was not the case for Mr C. Among 16 untreated patients who had
> neuroborreliosis in the 1970s, before the etiology of the illness was
> known, 14 developed oligoarticular arthritis months after the
> neurologic symptoms subsided.16 Typically, joint swelling and pain
> develop in one or a few large joints at a time, especially the knee,
> with intervening periods of complete remission.15 Knees often become
> very swollen, and the swelling is out of proportion to the pain. By
the
> time arthritis is present, the infection often seems localized to
> joints and systemic symptoms are minimal. Attacks of arthritis
usually
> recur over a period of several years or chronic arthritis may last
for
> this duration. However, even without antibiotic therapy, intermittent
> or chronic arthritis then resolves.15
>
> Rather than this pattern of arthritis, Mr C had severe
musculoskeletal
> pain and neuropsychiatric symptoms after his episode of facial palsy.
> He stated that he became "less and less competent mentally," lost the
> ability to perform simple math, and became depressed. The question is
> whether this clinical picture was caused by chronic infection of the
> nervous system with B burgdorferi. Following the period of
> oligoarticular arthritis, up to 5% of untreated patients have chronic
> neurologic manifestations of Lyme disease.17 In rare cases, a mild
> encephalopathy may develop, manifested primarily by subtle
disturbances
> in memory.17-18 Inflammatory changes are not found in cerebrospinal
> fluid, but intrathecal antibody production to B burgdorferi can often
> be demonstrated by antibody-capture enzyme immunoassay.19 In
addition,
> a chronic axonal polyneuropathy may develop, manifested primarily as
> spinal, radicular pain or distal paresthesias.20-21 In such patients,
> electromyograms typically show diffuse involvement of both proximal
and
> distal nerve segments. Currently, neither neuropsychological tests of
> memory, magnetic resonance imaging of the brain, nor single-photon
> emission computed tomography of the brain have sufficient specificity
> to be helpful in diagnosis.17, 22-23

It is Allen Steere who takes a VERY limited view of even the arthric
presentations in Lyme, and this piece suggests that much of it stems
from his original work (citing a 1987 article). In doing so he denies
all but the oligoarticular presentation has anything to do with Lyme
disease.

Again, what he calls Lyme is very narrow. Many patients with clear
evidence of the same etiologic agent found in Steere's Lyme patients,
have a much wider range of musculoskeletal manifestations. This
includes symptoms of arthralgias, diffuse pains, and arhtric
manifestations in addition to and or instead of the oligoarticular
manifestations.

It is actually the rare patient who presents with the big swollen knee
(which is usually seen in later stage disease meaning a misdiagnosis
occurred or inadequate treatment was given). And those who present with
polyarticular manifestations often have Lyme.

However, if you're allen steere and conduct studies where you make
oliogarticular frank manifestations a major entrance criteria and deny
other presentations as having anything to do with Lyme, then cite your
own articles which say that Lyme is only oligoarticular or
monoarticular presentations, well it is a self fulfilling prophecy.

I've read much of his work, and much of the work that cites his work
and that is what happens, all of this self fulfilling prophecy stuff.

So if you deny that low grade fevers, fatigue, joint aches without
"frank arthritic" manifestations, arthralgias, headaches, mental
confusion etc are LYme disease once and then continue to cite that
denial, for you it will never be Lyme even though patients with those
"vague symptoms" (medicine calls them "Vague" and it doesn't mean that
they're vague to the patient but rather difficult to objectively verify
for doctors--it is NOT my term) well then that won't ever be thought of
as "LYME" by you, even if those patients have very good evidence of the
presence of the same etiologic organism and other causes have been
ruled out.

It is substantial circular reasoning, poor science, poor medicine,
worse logic that leads Steere and those who cite his work to these
ridiculous and limited views, a priori and usually baseless assumptions
that operate as "givens" though there is no reason to accept them (such
as the use of the term "adequate treatment"--once you've been given
"adequate treatment" your symptoms can no longer be from Lyme--though
what in the world ever established a few weeeks of antibiotics as
"adequate" even steere's studies have documented treatment failure
rates of 30-35% and long term sequelae in patients given "adequate"
treatment and though at times he admits a "very few" patients might
need more, he cites the rareness of this to always deny it to everyone!
Astounding.

What gets me though is that his work is so filled with these obvious
flaws, methodological flawws, baseless assumptions, bad science, bad
medicine, worse logic, but it seems to be accepted so uncritically by
others!

I don't think the problem is failure to read the literature in the
field as greatcod suggests quite often. I think the problem is the
failure to read CRITICALLY, to parse the work, to seperate opinion from
science, to question methodology, to try to undertand the limitations
and limit the extrapolations from one type of patient to the entire
world of patients.

And what I also don't get is why infectious disease doctors,
neurologists, opthamologists, pediatricians, dermatologists,
psychiatrists etc all seem to be so deferential to the opinions of this
rheumatologist (and sigal too).

Typically in medicine one would expect to see the inf disease guys and
gals saying "well this is an infectious disease and he's ONLY a
rheumatologist, so perhaps he can shed some light on the rheumatologic
manifestations of the disease but hey WE'RE the experts about this--and
neurologists would say the same thing. Particularly when he's so
clearly wrong about so much and takes such a limited view of things
outside (and inside) his own field of expertise.

Again I just don't get it?

> Instead of a subtle encephalopathy or polyneuropathy, Mr C had severe
> musculoskeletal pain, neurocognitive symptoms, sweats, and fatigue.
> However, chronic neuroborreliosis cannot be diagnosed on the basis of
> symptoms alone. In addition to a positive antibody test result to B
> burgdorferi in serum, patients with Lyme encephalopathy often have
> intrathecal antibody production to the spirochete,19 and those with
> neuropathic symptoms typically have electromyographic evidence of an
> axonal polyneuropathy.21 Mr C had neither of these tests.

I think the perecentage of patients who have intrathecal antibody
production is actually LOW as is the percentage of patients who even
have such testing. And the incidence of axonal polyneuropathy isn't
necessarily very high either.

But, astoundingly, the absence of those things is considered
significant here--not because Mr C doesn't have those findings, but
because HE NEVER HAD THE DAMNED TESTS! So how could anyone logically
attribute any value to an absence of testing EVEN if a negative test
might add something (but not much).

Amazing!

> Diagnostic Testing
>
> How is Lyme disease diagnosed? The culture of B burgdorferi in
> Barbour-Stoenner-Kelly (BSK) medium permits definitive diagnosis, but
> this complex method has been performed only in research studies.
> Moreover, with a few exceptions, positive cultures have been obtained
> only early in the illness, primarily from biopsy samples of erythema
> migrans skin lesions,24 less often from plasma samples,25 and
> occasionally from cerebrospinal fluid samples.26 Later in the
infection
> in patients with Lyme arthritis, polymerase chain reaction (PCR)
> testing is greatly superior to culture for the detection of B
> burgdorferi in joint fluid,27 and this has been the major use for PCR
> testing in Lyme disease. However, this procedure, which must be
> carefully controlled to prevent contamination, is not routinely
> available. Neither culture nor PCR testing has been of much value in
> patients with chronic neuroborreliosis.

Well why in the world isn't PCR testing used more often? It is used in
MANY diseases. So why not Lyme? And it is always subject to issues of
contamination but that is easy--control for it. Use positive and
negative controls, clean rooms, UV lighting, and other universal
precautions when doing PCR testing. And with this organism it is NOT
floating around in the air (it is mostly aneorobic and the vector is
not airborne transmission).

So proper sample taking and handling and proper testing methods and an
adequately specific primer, PCR testing SHOULD be THE gold standard.
And it is good enough for Steere's studies and vaccine studies, so why
not for clinical use? It is NOT all that expensive.

And though I've heard this "contamination" issue bandied about, please
someone explain how it can't be dealt with? Where does the
contamination occur? One uses new needles and test tubes so it doesn't
occur at the point of taking the samples (and it isn't resident on
people's skin or floating around the office). If you use proper sample
handling and lab technique including positive and negative controls,
how is it an issue?

Sure a positive control can cause contamination but then the negative
control lights up. Sure once there is contamination it is hard to get
rid of but that means that all subsequent samples are going to be
positive unless and until decontamination is done. And one doesn't
expect to see sample after sample after sample after sample be
positive, so one gets a hint--and most labs run programs designed to
alert the lab to unusual patterns of findings like that.

So where's the freaking beef?

>Borrelia burgdorferi has not
> been cultured from cerebrospinal fluid in such patients,

I don't think the above is even accurate. It has been cultured from
such patients but cultured rarely (not never) and culture is
notoriously difficult so seldom done even in studies and pretty much
never done in clinical practice or labs.

So what?

>and B
> burgdorferi DNA has been detected in cerebrospinal fluid in only a
> small number of cases.28 Finally, the urine antigen test, which has
> given grossly unreliable results,29 should not be used to support the
> diagnosis of Lyme disease.

I agree that the LUAT is not reliable and IGenex never proved that it
was in response to klempner's study so that one is pretty much
checkmate klempner at least as far as we know (rather than suspect
sabotage it has never been proven and igenex really dropped the ball on
responding).

> Because of the problems associated with the direct detection of B
> burgdorferi, the diagnosis of Lyme disease is usually based on
> recognition of a characteristic clinical picture,

The problem is that very few patients present with the "characteristic
clinical picture" that Steere DOGMATICALLY AND RIGIDLY INSISTS UPON and
many patients who definitely have evidence of the same etiologic agent
that he sees in those he gives the Lyme diagnosis to, present with
variant clinical presentations, not so characteristic, quite
heterogeneous in fact.

> exposure in an endemic area,

But one has to consider ANY exposure (in your own backyard) in any area
which is endemic or even has Lyme, which a patient not only lives in
but travels to or recreates in no matter how infrequently and given
delays in diagnosis, perhaps temporally distant particulary considering
the possibility that the disease was dormant or latent and now has
reemerged.

One needs to consider syphillis in neurological patients in comitted
marriages who have never cheated even if their last contact other than
with their partner was decades ago!

>and except in patients with erythema migrans, a positive
> antibody response to B burgdorferi by enzyme-linked immunosorbent
assay
> (ELISA) and Western blot, interpreted according to the criteria of
the
> Centers for Disease Control and Prevention and the Association of
State
> and Territorial Public Health Laboratory Directors (BOX 1).30-31

Well first the EM might be atypical and not a bullseye. Second, the WB
criteria cited are ridiculously narrow for no good reason and exlude
specific and unique bands insisting on an unrealistic combination of
bands to appear simultaneously, and many many probably 35% or more are
definitely Lyme patients who won't meet those criteria and using the
ELISA as a screening test is absurd mathematically scientifically and
medically because of the high rate of false negatives. In the vaccine
trials 35% or more were "Seronegative" by those standards but PCR
positive.

>During
> the first several weeks of infection, when most patients have
erythema
> migrans, serodiagnostic tests are insensitive and depend primarily on
> the detection of an IgM response to B burgdorferi.32-33 However,
after
> 4 weeks of infection, by which time most patients have disseminated
> infection, the sensitivity and specificity of the IgG response to the
> spirochete are both very high, in the range of 95% to 99%, determined
> by the 2-test approach of ELISA and Western blot.33

This is just demonstrably not true. Yes early on due to the vagaries of
the antibody response as it develops the tests are not sensitive. But
later on the tests are NOT sensitive or specific at anything
approaching those rates. The ELISA is, at best, 40-60% accurate if one
takes into account false negatives not just "false positives" as Steere
has redefined the term. And the WB using those criteria is not great
either, maybe 60-80% sensitive depending on a number of factors. If one
combines the error rate of using a test that might be only 40-60%
sensitive to "Screen" and then only test the positives, using a test
that itself is only 60-80% sensitive, one obviously misses HUGE swaths
of patients.

Also, since when is a "clinical" diagnosis, dependent on demonstrably
unreliable testing?

Again, what is at work here is figures lying and liars figuring and
circular reasoning and self fulfilling prophecies and proceeding from
baseless a priori and dubious at best assumptions.

> In persons who have
> been ill for longer than 1 month, a positive IgM finding alone is
> likely to represent a false-positive result; therefore, such a
response
> should not be used to support the diagnosis of Lyme disease after the
> first month of infection.

Even though Steere himself has written about and documented a recurring
IgM response as being indicative of recrudescing and/or chronic
disease?

When it suited him at least.

> In rare instances, patients who are incompletely treated with
> antibiotics during the first several weeks of infection, prior to the
> development of a humoral immune response to B burgdorferi, may
> subsequently experience subtle joint or neurologic symptoms without
> accompanying humoral reactivity to the spirochete, a phenomenon
called
> seronegative Lyme disease.34

Rare? Rare that Steere admits it. But several of his studies have
documented treatment failure rates which are high as high as 35% and
that uses fairly generous definitions of "success" and only short term
follow up.

And one of his long term follow up studies documented a great deal of
long term sequelae after using such treatment.

So how does he define rare, other than he rarely admits it or admits
that it is due to Lyme?

EVEN IF IT WERE "RARE" so what? Does that mean that a patient who has
that presentation can NOT be a Lyme patient? What is rare? If it
happens to 5% of people, well that is 5 of 100, 50 of 1000, 500 of
10,000, 5000 of 100,000, 10,000 of 200,000.

And if one accepts that there are now 25000 or so CDC cases, that means
that we'd see 1250 cases a year--if one accepts that the CDC figures
are only 10% of CDC qualified cases, it would be 12,500 cases a year,
if one accepts that CDC undercounts many lyme cases and maybe there are
twice as many (after all surveillance excludes definite cases, is not
for diagnosis, and there is underreporting by a factor of ten according
to the CDC and it might even be 15 or 20 times underreported) and there
is 500,000 cases a year one would see 25,000 cases a year of a RARE
manifestation!

See, that is one way that figures lie and liars figure--a low
percentage may actually be a high number. So is he denying that
thousands of people exist?

>However, in contrast to Mr C's course,
> such patients have a mild, attenuated clinical picture, and their
> symptoms respond well to standard courses of antibiotic therapy.35

According to Steere YES--self fulfilling propehcy a priori assumption
substantial circular reasoning bad science bad math bad medicine worse
logic.

> Although seronegative patients may have cellular immune responses to
B
> burgdorferi as determined by proliferation assay, this test is not
> recommended for support of the diagnosis of Lyme disease because of
> problems with standardization.34

Well standardize it! I mean this issue has been known since the early
80s. 20 years later now. When are you going to get on the ball?

> In Mr C's case, serologic testing was first done in 1994,
approximately
> 2 years after the episode of facial palsy. A screening ELISA test
using
> a polyvalent conjugate (IgM and IgG) was positive with a value of
1:4,
> just above the usual cut-off of 1:0. A value in this range may well
> represent a false-positive result, particularly since a polyvalent
> conjugate was used. Among patients with late infection, the value
would
> usually be considerably higher. In a patient who had the illness for
2
> years, it would be necessary to show that the IgG result was positive
> by 2 tests, ELISA and Western blot, before concluding that the
> serologic test result was positive.

Yawn. See above. These tests SUCK.

> Five years later, Mr C's serum was tested with a Western blot assay
but
> apparently not with ELISA. The only positive band, using the criteria
> of the Centers for Disease Control and Prevention, was an IgG
response
> to the 41-kd flagellar protein of the spirochete.31 About half of
> healthy control subjects have sera that react with this protein;
> therefore, this response, by itself, has no diagnostic
significance.33

What about his 83 band?

> Although the antibody response may be aborted by antibiotic treatment
> during the first several weeks of infection,34 it is unlikely that a
> positive response could have been abolished by the many courses of
> antibiotic treatment Mr C received later in the infection. Of 39
> patients who had late Lyme disease 10 to 20 years previously, 6 (15%)
> had low-level IgM responses and 24 (62%) still had moderate to high
IgG
> responses to B burgdorferi, determined by the 2-test approach of
ELISA
> and Western blot.36 Moreover, in most of the patients who were
> classified as having negative results by the 2-test approach,
low-level
> IgG reactivity was still apparent by ELISA, and 3 or 4 bands were
> present on Western blot rather than the requisite 5 or more bands.
> Because the antibody response to B burgdorferi commonly persists for
> years after active infection, serologic testing demonstrates exposure
> to the spirochete but does not distinguish between past or active
> infection. This is the major limitation of serologic testing.

Yes it is.

> I would conclude that Mr C's illness did not meet the criteria of the
> Centers for Disease Control and Prevention for the diagnosis of Lyme
> disease.

Okay but those are SURVEILLANCE NOT DIAGNOSTIC criteria! So what?

>He had exposure in an endemic area for Lyme disease and his
> illness began during summer with a possible neurologic manifestation
of
> that infection. However, his subsequent clinical course was not
> characteristic of untreated late Lyme disease, and he did not have
> serologic evidence of B burgdorferi infection.

Gee this guy IS annoying. And very unprofessional. He (and we) need to
know MUCH more about differential testing and other results (ESR, lfts,
both of which can be elevated in Lyme) and so much else!

> Antibiotic Treatment
>
> Mr C was treated with many prolonged courses of tetracycline over a
> 5-year period, and he also received several courses of clarithromycin
> and hydroxychloroquine. During a 1-year course of antibiotic therapy,
> he felt progressively better but never totally well. When the
> antibiotics were stopped, severe pain recurred and antibiotic therapy
> was reinstituted.

So doesn't that show the abx were doing SOMETHING? Lyme or not, they
were helping even if not totally curative.

So back to resistant TB--if every doctor took that attitude that a
patient who was improving but not cured by the "Standard" conventional
course of treatment (prior to resistant tb) clearly didn't have TB
since they weren't CURED, then lots of patients would be dying of TB
that the doctors refused to acknowledge was TB out of sheer obstinance
and narrow mindedness.

> Is there evidence that B burgdorferi may persist for years despite
> multiple, prolonged courses of antibiotic treatment? In one European
> study,37 B burgdorferi was isolated from cerebrospinal fluid or skin
> biopsy samples of 3 patients each, months after treatment with 10 to
14
> days of oral or intravenous antibiotic therapy for erythema migrans
or
> acute neuroborreliosis. Those authors postulated that the spirochete
> may develop spheroplast L-forms, which could survive despite
antibiotic
> treatment.38

Well that sure isn't the ONLY study demonstrating persistence of the
organism.

> However, the long-term persistence of the spirochete has
> not been substantiated in any large series of patients treated with
> currently recommended regimens, in either Europe or the United
States.

So? Does that mean it doesn't happen? Sheesh!

> In 2 large retrospective analyses, B burgdorferi DNA was not found in
> the joint fluid or cerebrospinal fluid of patients with Lyme
arthritis
> or chronic neuroborreliosis after 2 or more months of oral
antibiotics
> or at least 1 month of intravenous antibiotics,27-28 suggesting that
> the spirochete had been eradicated by this treatment.

Or suggesting that the testing SUCKED and the patients were VERY
atypical due to the ABSURD entrance criteria for the lousy NIH study!
Patients were exlcuded if they were thought to actually have persisting
infection in the first place so the failure to find it proves, what?
That those patients with it weren't allowed in to the study which
doesn't prove that those who did have it, can't have it.

I mean, how does any of this pass the basic tests for logic?

>Borrelia
> burgdorferi has only been seen extracellularly in affected tissues39;
> the organism has not been shown to "hide out" in intracellular
> locations for prolonged periods and thereby evade antibiotic
exposure.

Sure it has and even Yale recently documented it!

> According to evidence-based recommendations presented by the
Infectious
> Diseases Society of America, the various manifestations of Lyme
disease
> can usually be treated successfully with oral doxycycline or
> amoxicillin, except for objective neurologic abnormalities, which
seem
> to require intravenous therapy, usually with ceftriaxone (BOX
2).40-41
> In most instances, 14 to 28 days of treatment is sufficient.

"USually" be succesfully treated. Based on steere's studies ignoring
the high treatment failure rates. So what anyway? What about the
UNusual cases, no matter how often they occur.

Do they get no treatment because they fall out of an arbitrarily
determined group?

I mean really this stuff is so obviously absurd.

>With these
> regimens, more than 90% of patients with early infection have had
> satisfactory outcomes.42-43

But many many many patients are NOT diagnosed early or treated early.
Even if it were only 10% that means a LOT of patients are not
succesfully treated:

25000 CDC qualified cases a year, 10%=2500

250,000 CDC qualified cases using the CDC admission to reporting of
only 10% of qualifiable cases, 10%=25000 a year

500,000 (using a formula calculating CDC qualifiable cases, those the
CDC excludes, misdiagnosis and I think that might be conservative), 10%
=50,000 annually--that is EVERY YEAR!

So that is actually a LOT of people who are getting screwed even using
steere's 90% success rate figure, and I think that is pretty generous
to him and ignores his own higher treatment failures and accepts his
self servingly generous and short term follow up based definition of
"success" in treatment.

So how can you deny the others?

Listen, most West Nile Virus is asymptomatic or self limited. Only a
tiny fraction of patients who are exposed have serious disease. But we
don't deny their exitstence in fact a LOT of attention is focused on
them and that disease (by the way, ever notice that there is not a
single WNV support group in the nation but there are dozens of Lyme
groups? Why is that?).

>Although some patients have subjective
> symptoms after treatment, objective evidence of relapse has been
rare,
> and retreatment has not usually been needed.

In your freaking narrow opinion and definitions Steere.

> Patients with
> encephalopathy or polyneuropathy, the typical manifestations of
chronic
> neuroborreliosis, have usually responded to treatment with 4-week
> courses of intravenous ceftriaxone.20-21,44 Although their symptoms
> changed little during treatment, these patients usually improved
slowly
> during the following 2 to 6 months and relapse was rare. In contrast,
> Mr C's symptoms improved while taking antibiotics, and they recurred
> each time that treatment was stopped.

Bull***.

> Post-Lyme Disease Syndrome or Chronic Lyme Disease

Okay more later. I'm sick of this and getting really pissed.

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