From
the LymeLight Newsletter of the Lyme Disease Foundation
The controversies
surrounding Lyme Disease diagnosis and treatment and why it is
not uncommon for patients to experience persistent symptoms despite
receiving conventional" (short-term) antibiotic therapy
for Lyme disease.
"Randomized
controlled studies of treatment of patients who remain unwell
after standard courses of antibiotic therapy for Lyme disease
are in progress. To date, there are no convincing published data
that repeated or prolonged courses of either oral or iv antimicrobial
therapy are affective for such patients. The consensus of the
Infectious Disease Society of America (IDSA) expert-panel members
is that there is insufficient evidence to regard "chronic
Lyme disease" as a separate diagnostic entity."
So reads the most disturbing statement in the latest Lyme disease
diagnostic and treatment protocol, formulated by the Infectious
Disease Society of America (IDSA) and published in the September
issue of Clinical and Infectious Diseases (2000; 31:1-14). Not
surprisingly, the protocol dismisses the existence of chronic
Lyme and provides clinicians with a virtual "four weeks
cures all" protocol. The LDF expected the contents of the
protocol after it discovered internal National Institutes of
Health (NIH) documents that confirm the IDSA protocol was coordinated
with a CDC-funded protocol to ensure they were identical. Another
unsurprising aspect of the protocol is that it does not disclose
IDSA committee members' conflicts-of-interest, as some committee
members consult for insurance companies and Health Maintenance
Organizations.
The IDSA's
chronic Lyme disease (LD) statement is especially troubling because
it comes during a time when physicians who recognize and aggressively
treat late-stage LD are being charged by state licensing boards
with overdiagnosis and overtreatment of the disease. For such
doctors the protocol adds another "authoritative" document
dictating "appropriate management" of a disease in
which treatment failure can occur in any stage and no test can
definitively diagnose or distinguish active from past infection.
Adding further confusion to doctors trying to responsibly help
patients is that no consensus has been reached about the clinical
spectrum of LD, which the Centers for Disease Prevention and
Control (CDC) states is a clinical diagnosis not to be ruled
out based on negative tests.
"The
implications of the guidelines are chilling," said Kenneth
Liegner, M.D., a LD specialist from Armonk, NY, an area hyperendemic
for Lyme disease. "They place physicians who treat beyond
[IDSA] parameters in an extremely defensive position." Sam
Donta, MD a Boston University Hospital infectious disease specialist,
has already experienced the impact IDSA's statement is having
on other clinicians. "Patients have already told me doctors
are telling them there is no such thing as chronic Lyme disease,"
he said.
Donta, who
like Liegner treats late-stage LD patients from around the country
with longer-term antibiotic therapy, said he too was stunned
that the Society could come to such a conclusion, especially
since the National Institutes of Health (NIH) believes in chronic
LD enough to study it.
Many physicians
and researchers voice displeasure that since Lyme was supposedly
"identified" in and around Lyme, Connecticut in 1975
by rheumatologist and IDSA committee member Allen Steere (a medical/insurance
consultant), he and a few of his colleagues have become crowned
"leading authorities" on LD. They say the approach
they and the CDC take studying the disease continues today: minimize
medical costs associated with the disease by downplaying its
seriousness and defining it in the narrowest terms possible.
Such an approach limits patient access to tests, reduces the
official number of patients reported to have the disease, and
reduces treatment costs, they say.
Initially
Steere believed LD was a viral arthritis that affected only children,
its symptoms were limited to arthritic conditions, and the disease
eventually went away on its own. Southeastern Connecticut shoreline
towns were thought to be the only place in the country where
one was at-risk for the disease. It was also believed neurological
manifestations of LD, common in Europe, did not occur with US
strains of the LD bacterium, Borrelia burgdorferi, (Bb).
As science
evolved, Steere and his colleagues, most of which continue to
receive large government grants to study the disease, were slow
to acknowledge Lyme is often a multisystemic disease. As it became
apparent that symptoms often did not disappear on their own,
they acknowledged antibiotic treatment was sometimes necessary
to eradicate the Lyme bacteria. They steadfastly maintain, however,
that short-course antibiotic therapy is highly curative, seronegative
disease is rare, and patients who remain symptomatic after treatment
suffer from misdiagnosis or "post Lyme syndrome", which
attributes persisting symptoms to past, not active infection.
While initial
conclusions about the disease have been modified, their narrow
definition of the disease allows the most conservative conclusions
relative to diagnosis and treatment to be made. Patients in late
disease with severe neurologic symptoms, which are the most problematic
to diagnose and difficult to cure, rarely meet the narrow CDC
surveillance criteria (e.g. swollen joint(s) and positive two-tier
tests) used as inclusion criteria for research studies. As a
result, a large void in Lyme research exists.
Testimony
by IDSA committee member/insurance consultant Raymond Dattwyler,
MD during a 1994 Food and Drug Administration (FDA) meeting on
the Lyme vaccine reveal enough gray areas in scientists' understanding
of the disease to suggest standardization of diagnosis and treatment
of LD is not yet possible. Nationally-based treatment trials
of erythema migrans, Dattwyler said, may suggest regional differences
in patients' symptoms and response to antibiotic therapy due
to many different strains of Bb found throughout the U.S. Dattwyler
also testified that patients who mount a weak immune response
to the disease tend to have worse disease and a greater chance
of treatment failure than do those who mount a vigorous immune
response.
In addition,
Dr. Dattwyler echoed the consensus among experts concerning the
relationship between the LD bacteria and how it affects humans.
"I don't think we have fully delineated all the various
clinical manifestations associated with this infection,"
he said. Several times throughout his testimony Dattwyler repeated
that sentiment.
Dr. Liegner
has concerns that suggest IDSA bias against the existence of
chronic LD. "It's amazing that the Committee ignored piles
of published case studies detailing chronic Lyme because they're
not double-blinded peer-reviewed studies," he said. Liegner
went on to echo the consensus among he and his colleagues: In
lieu of the absence of such research and disagreement among experts
over the etiology and clinical spectrum of the disease, there
are no "evidence-based" experts qualified to determine
appropriate standards of care for LD. Therefore, Liegner said,
empirical treatment, or treatment based on patient response,
should be the standard of care.
Dr. Liegner
also expressed concern that out of 99 studies cited in the protocol,
only two examines chronic LD. One cited study by Dr. Steere,
"Chronic neurologic manifestations of Lyme disease"
(N Engl J Med 1990; 323:1438-44) evaluated the outcomes of patients
with late neurological LD symptoms when treated with iv ceftriaxone
(2 grams daily for two weeks). Of 27 adult patients, 17 (63%)
of patients had "uncomplicated improvement." 6 (22%)
had improvement and then relapsed and 4 (15%) had no change in
their condition. Regardless of this study's 66% "uncomplicated
improvement" rate, IDSA recommends treating late neuroborreliosis
with 2-4 weeks of ceftriaxone. Guidelines state "response
to treatment may be slow and incomplete." Unless relapse
is shown by "reliable, objective measures" repeat therapy
is not recommended.
An abstract
presented by IDSA committee member Dr. Dattwyler at the VII International
Congress on Lyme Borreliosis in 1996 revealed similar statistics.
That study evaluated the effectiveness of intravenous orintramuscular
injections of ceftriaxone, 2 grams daily, for 2 versus 4 weeks.
Patients in the study had to have objective evidence of a usculoskeletal,
neurologic or dermatologic disorder compatible with the diagnosis
of LD and positive ELISA and Western blot tests.
The abstract
reported clinical cure rates of 76% for patients treated for
14-days and 70% for those treated with 28-days. While the 28-day
group had a lower efficacy rate, patients in this group were
"more severely ill" than those treated for two-weeks.
(No data concerning patients' specific immune response was included.)
To be eligible
for the study, patients must have had an erythema migrans or
exposure to an endemic area no less than 3 months prior to enrollment.
Therefore it is likely most patients, if not all, were infected
less than four months prior to treatment. Doctors such as Liegner
and Donta find the hardest patients to treat are those who are
likely to have been infected many months or even years before
getting diagnosed.
Despite assertions
by Dr. Dattwyler that a positive test stands a 98% chance of
being a false-positive (1993 WLIW TV interview), the protocol
does not explicitly state what constitutes "reliable, objective
measures" that would warrant extended therapy when i.v.
treatment fails to alleviate symptoms of neroborreliosis. Using
direct-detection tests such as PCR, the experience of front-line
physicians like Donta and Liegner find such short duration therapy
in late stage cases is not likely to eradicate the LD spirochete.
They find several months or more of therapy is often required
before a patient is symptom-free/relapse free. In some patients,
restoration of prior health may not be possible.
Many case
reports support the adaptation of a longer-term treatment approach.
Liegner has published case studies detailing Bb's ability to
evade antibiotic destruction, including "Recurrent erythema
migrans despite extended antibiotic treatment with minocycline
in a patient with persisting Borrelia burgdorferi infection"
(Journal of the American Academy of Dermatology, 1993; 28: 312-314).
Numerous full text articles detailing persistence or relapse
of LD despite "appropriate" or "conventional"
antibiotic therapy have also been published in peer-reviewed
journals.
Among the
most compelling published evidence of chronic infection despite
prolonged antibiotic therapy is the case study "Seronegative
Chronic Relapsing Neuroborreliosis," (Eur Neurol 1995; 355:
113-17). It details a patient whose serum was consistently negative
for free antibodies for Bb infection, but had laboratory evidence
of active infection in the cerebrospinal fluid (CSF). The patient,
a previously healthy 58-year-old woman, received four courses
of intense antibiotic therapy: 3-weeks of intravenous ceftriaxone
followed by 8-weeks of ceftriaxone; 2 weeks of intravenous ceftriaxone
followed by 19 weeks of doxycycline; 3-weeks intravenous treatment
followed by additional treatment with doxycycline; and 2 weeks
of intravenous ceftriaxone.
Evidence of
active infection was found each time after intense prolonged
antibiotic therapy was administered. Relapse occurred soon after
treatment was stopped and Jarish-Herxheimer episodes were experienced
each time treatment was initiated. (J-H reactions are symptoms
that include fever and nausea and are believed to be cause by
the body's initial reaction to toxins from dead Bb.) When the
patient was given clarithromycin for 22 months, no new symptoms
or deficits occurred.
The report
concludes the case is "an unusual case of seronegative Lyme
disease" in a patient with "chronic relapsing Bb infection."
Renowned neuro-Lyme expert and IDSA committee member Patricia
Coyle, MD, SUNY Stony-Brook School of Medicine, co-authored the
article. She did not respond to Email requests to discuss the
IDSA protocol.
In addition
to its rebuttal of chronic Lyme and endorsement of a short-term
protocol, the way the Society conducted itself while formulating
the guidelines remains a concern to many scientists. Dr. Donta
was originally a member of the IDSA while it was drafting the
protocol. He says the committee "disbanded" after years
without success of trying to agree on anything beyond diagnosis
and treatment of early-stage disease. He said during his time
on the committee, no statement on chronic LD was included in
the protocol's original draft.
When Donta
learned the guidelines were going to be published, he said he
voiced his desire to make changes to its late-stage section.
Rather than consider his suggestions, Dr. Donta said committee
member Robert Nadelman, MD, informed him that unanimity was not
required for publication, and Donta's name was removed from the
protocol without explanation. For reasons that remain unclear,
the protocol was taken from committee chair Benjamin Luft, who
Donta believes wanted to make changes to its late stage section,
and given to Dr. Gary Wormser, an insurance consultant (Aetna)
who took over as IDSA chair during the reorganization of the
committee. Dr. Donta previously told LymeLight he believed the
IDSA meetings "were based on politics, not science"
and that when the guidelines were published, they would be "an
embarrassment to the Society." Dr. Luft did not return messages
to discuss the protocol.
Documents
obtained by the LDF support Donta's conclusion. In a October
1995 e-mail, former NIH Lyme Disease Program Officer Edward McSweegan
(who was removed from his position), tells new NIH Lyme Disease
Program Officer Phil Baker that the American College of Physicians
(ACP) and IDSA are currently working on Lyme disease diagnostic
and treatment protocols. McSweegan says Dan Rahn, who was in
charge of CDC-funded ACP protocol and an IDSA member for the
LD protocol, is "supposed to be talking with" IDSA
chair Benjamin Luft, MD to "avoid duplication incompatibility."
Rather than "copy the wheel," (presumably by writing
a third identical protocol), McSweegan suggests NIH find a way
"to support the current efforts or provide some kind of
endorsement for them."
Adding further
suspicion of collusion to establish one specific protocol for
LD diagnosis and treatment is a portion of the book "Lyme
Disease" authored by IDSA-committee membr Dan Rahn,M.D.,
M.P.H., and Yale physician Janine Evans, M.D., and the American
College of Physicians. Page 199 of the book states: "Nationwide,
efforts are well underway to limit practice variation, reduce
unnecessary health care expenditures, and measure and improve
patient outcomes." Not only might this pertain to avoiding
"duplication incompatibility" on authoritative LD protocols,
but also one must wonder its relevance to the nationwide harassment
of physicians by state health departments against doctors who
deviate from "authoritative" protocols such as the
IDSA's and treat beyond their recommendations.
Reached at
his office at the Medical College of Georgia (MCG), Dr. Rahn,
Chair of the MCG-Blue Cross/Blue Shield Center of Health Care
Improvement, said no effort was made to coordinate protocols
and that the paragraph in question simply pertains to analyzing
if Lyme patients are receiving "the known best practice
by leading authorities" for diagnosing and treating LD.
As an example, Rahn cited "Quality of Medical Care Delivered
to Medicare Beneficiaries" a study in the October issue
of Journal of American Medical Society (JAMA 2000;284:1670-1676).
The study analyzes quality of care Medicare recipients receive
for primary prevention, secondary prevention and/or treatment
of 6 medical conditions (e.g. stroke) for which there is "strong
scientific evidence and consensus that the process of care either
directly improves outcomes or is a necessary step in a chain
of care that does so." In light of polarized medical and
scientific communities over the diagnosis/treatment and clinical
spectrum of LD and ongoing NIH studies examining the issue of
chronic LD, it seems such a study for Lyme cannot be done on
a scientific basis.
Likewise,
efforts to "standardize" diagnosis and treatment protocols
would be, at best, premature. Though Rahn cited the JAMA study
as an example what his book referred to, he offered no specifics
as to what similar studies may have been "well underway"
when the book was published in 1997.
It is such
suggestions as Dr. Rahn's that make many Lyme doctors such as
New Jersey physician Anthony Lionetti irate. "Right now,
it is impossible to formulate any protocol for Lyme that goes
beyond early stage disease," Lionetti said. "Thousands
of treated patients experience persisting symptoms despite 28-days
of treatment. How can we standardize their treatment when there
is not one double-blinded, controlled study that examines how
they respond to additional antibiotic therapy." Lionetti
estimates he has treated over 1,000 late-stage Lyme patients.
For the majority of those, he prescribes a maximum of eight weeks
of intravenous antibiotic therapy and estimates the success rate
by treating with such duration is "about eighty to ninety
percent."
New York State
Office of Professional Medical Conduct's trial against East Hampton
doctor Joeseph Burrascano, Jr., on charges of overdiagnosis/treatment
of LD and its revocation of Long Neck Lyme specialist Perry Orens,
MD, last year exemplifies the "chilling" impact Liegner
and others believe the protocol will have on Lyme docs who aggressively
treat late-stage LD. After leaving Burrascano's case open for
over six years, OPMC informed him just weeks after the protocol
was first released in late August that they will proceed with
their case against him. The opening date of his trial took place
October 26. LDF chair Karen Vanderhoof-Forschner anticipates
the IDSA protocol will be among the primary evidence used against
Burrascano.
Though Burrascano
cannot reveal the specific charges against him, media reports
state the charges include overdiagnosis and overtreatment of
LD. The case represents a pivotal chapter in the Lyme disease
controversy, as Burrascano is perhaps the most vocal, respected
and influential physician who recognizes and aggressively treats
LD. With his Lyme disease diagnosis and treatment protocol published
in Conn's Current Therapy (Rakel, 1997), many Lyme-literate doctors
rely on his guidelines to diagnose and treat LD.
Should Burrascano
lose his case, the ever-shrinking list of doctors willing to
aggressively treat patients who remain symptomatic after "conventional"
short-term therapy because of unscientific protocols such as
the IDSA's is sure to become even shorter.
And the implications
of that go far beyond chilling.
To download
a copy of the Infectious Disease Society of America's Lyme disese
protocol .
