A 19 year old male came into my office yesterday for follow up for meningitis diagnosed at his college campus. One month prior to our visit he experienced acute onset of fever, chills, sweats, weakness, headache and stiff neck. He was admitted to the local hospital with a presumptive diagnosis of meningitis. A spinal tap was performed and he was give a single dose of Vancomycin. The results of the CSF (spinal fluid) were reported negative and no further antibiotics were given. He was noted to have a low white blood cell count which subsequently improved. He was diagnosed with viral meningitis and sent home on no treatment. A week after his discharge from the hospital he received a call from the hospital. A blood test showed antibodies to Ehrlichia. He was treated with Doxycyline, 100 mg twice daily for 10 days. He complained that symptoms persisted and the Doxy was renewed for an additional 14 days.
When he came to see me he was still not feeling well. He had persistent low grade headaches, severe fatigue and generalized malaise.
Over the last several years I have seen many patients who have been diagnosed with viral meningitis who have in fact suffered with acute Lyme meningitis.
Although Ehrlichia infection can exist without concomitant Lyme I felt that this was unlikely. Ehrlichia meningitis is extremely rare although a few cases have been reported. In this case the positive serology for Ehrlichia tipped my hand that the "viral meningitis" was actually caused by Lyme disease.
Ehrlichia can be difficult to eradicate since it resides in white blood cells.
For this patient I prescribed Doxycyline 400 mg per day and Rifampin 600 mg per day. This is the most effective combination for Ehrlichia and also covers Lyme disease.
Based on the clinical response future treatments may need to focus more on Borrelia.
I await initial lab studies and will see this patient back in one month.
Tuesday, March 10, 2009
Monday, March 9, 2009
As the IDSA reviews it 2006 guidelines.....
As the IDSA reviews its 2006 Lyme disease guidelines, it should be reminded of its own statements regarding disease guidelines: "Guidelines are...developed...to assist practitioners and patients in making decisions about appropriate health care for specific clinical circumstances. "Attributes of good guidelines include validity, reliability, reproducibility...clinical flexibility, multidisciplinary process, review of evidence..." The IDSA states that: "It is important to realize that guidelines cannot always account for individual variations among patients. They are not intended to supplant physician judgment...adherence to the guidelines...(is) voluntary..."
Unfortunately, the 2006 Lyme disease guidelines have morphed into something which they are not- a template for the determination of the standard of care regarding the diagnosis and treatment of Lyme disease and tick borne disease. Standards of care are known to vary within different medical communities. Clearly two standards exists. Both ILADS and the IDSA have evidence based guidelines for Lyme disease, which have been vetted be the United States Department of Health and Human Resources and are listed with the National Clearing House of Guidelines.
Lyme is frequently seen as the most controversial and perhaps the most important disease of our times. The IDSA guidelines must be seen in their proper context: they represent the opinions of panel members who were assigned the task of creating said guidelines. Although the guidelines may be based on evidence, ultimately they reflect opinion. It should have been noted that not all panel members were unanimous in their support of the conclusions drawn therein. The existence of strident rejections of guideline conclusions by at least one prominent panel member deserves mention. After all, what is being contested here is the validity of one particular paradigm, supported by the IDSA. In essence, this discussion can be characterized as a war between two diametrically opposed, competing paradigms. To that extent, I believe it is disingenuous when the IDSA either wittingly or unwittingly, promotes the notion that panel members were all in agreement. When a subject is this important, and when the disagreements are so vitriolic, minority opinions become important and should be reported. Similarly, the current requirement that of a quorum of 75% amongst new panel is required to consider revision of the 2006 guidelines is problematic. The IDSA is obligated to report that Lyme disease and the IDSA guidelines remain very controversial. History tells us that paradigms in science and medicine do not easily shift. Not terribly long ago, two scientist were ridiculed by their colleagues for suggesting that peptic ulcer disease was connected to a small bacterium seen in the gastric lining of patients. History later proved that these two pioneers were correct and they were awarded a Nobel prize in 2005.
With this in mind, let us review some of the evidence. The two tier diagnostic test for Lyme disease is simply not valid for the diagnosis of Lyme disease. This test was developed as a surveillance test by the CDC in 1994, not a diagnostic test. It is well known that specific bands 31 and 34 were omitted from the surveillance Western Blot. The United States Congress admonished the CDC to correct the misuse of this test. To date this has not happened. Under oath, CDC representatives, in the Connecticut hearings, reiterated that the test was a surveillance tool and that the diagnosis of Lyme disease was largely clinical. It is an outright embarrassment that the IDSA clings to the incorrect use of the test, stubbornly holding that it is an accurate, evidence based tool for the diagnosis of Lyme disease.
The three NIH sponsored studies looked at a narrow population of Lyme patients: Those who had been previously treated but had persistent symptoms. There are many other groups of patients suffering with Lyme disease who are not included in the cohort which was studied. For example, Some patients have had the disease for years or even decades and yet never sought treatment prior to their initial request for medical care. Many patients are co-infected with Babesia, Ehrlichia and/or Bartonella which may interact with Lyme disease as a syndrome or complex, in ways which have not been studied or established. Some patients are diagnosed with neuroborreliosis showing significant mental status changes with abnormal MRI scans and PET or SPECT scans. Other patients have refractory arthritis as their primary syndrome. These patient types represent the tip of the iceberg. Lyme disease is a multisystem disease associated with protean clinical manifestations. Even if the results of the three NIH studies were in accordance, which they arguably are not, it would be bad science to generalize such results to have wide ranging clinical applicability for many different clinical presentations and patient types suffering with Lyme disease.
The studies were small pilot studies and do not reach the same conclusions. The Klempner study has been widely criticism for a plethora of procedural deficiencies.
Patients with evidence of active Lyme disease- PCR positive were excluded. Test subjects included those who were seropositive as well as those who were seronegative. This is confusing since a key IDSA point is that the standard serological test is accurate. How then was the serogneative-PCR negative test group validated? Assuming the seronegative group did indeed have Lyme disease, how can the two subgroups be combined as a single cohort? The number of study subjects was smaller than the requisite number required by the study design. There is no agreed upon the definition of what constitutes long term therapy. For that matter, the correct choice of antimicrobial therapy has not been agreed upon or has the manner in which it should be administered. For example, perhaps the treatment group would have responded more favorably if the 2 months of oral doxycyline preceded the 30 days of IV Rocephin? The study was vary narrow in its design and outcome measurements. The use of these results to support far reaching conclusions, as has been frequently done, would seem to be bad science at best.
The Krupp study was a rehash of the Klempner trial. In this case patients were treated for 28 days with Rocephin. The results were not entirely negative. Patients with severe fatigue were shown to experience improvement. It was not known what outcomes may have been found if the study was extended to 8 or 12 weeks.
The results of the Fallon study were not available at the time the 2006 guidelines were developed. Here a group of individuals with severe neuroborreliois where shown to have cognitive improvements after 10 weeks of Rocephin. That fact that the improvements were not sustained is not evidence that the therapy did not work. It could be easily construed as evidence that the therapy was inadequate. For example, it is not know whether the cognitive improvements would have been sustained if the IV therapy had been continued- or if Rocephin therapy had been followed by continued oral antibiotic treatment for some period of time.
The guidelines are supposed to include multidisciplinary inputs. Where are the contributions of molecular biologists, microbiologists, immunologists and many others? Borrelia burdorferi has been demonstrated to persist in human and animal hosts in the face of extensive exposure to antimicrobials. Borrelia burdorferi has more plasmids than any other known bacteria. It has numerous mechanisms for evading eradication by the immune system and antibiotics. It has the ability to shift its antigens as has been amply demonstrated. It has the ability to live and proliferate in various protected niches. It has the ability to change its morphology and shift into intracellular L-forms and cystic forms. It is known that intracellular bacteria are not amenable to acquired humoral responses and that immunological defenses are mediated by innate immune responses. These innate responses, as has been shown with numerous other intracellular bacteria, frequently fail to completely eradicate the offending bacteria. Bb has the demonstrated ability to readily cross the blood brain barrier causing persistent infection and inflammation. The immune privileged brain allows a protective niche for long term survival. A large repertoire of well documented basic science, published in respected, peer reviewed journals describing the morphology and complex biological activity of Bb, both in vitro and in vivo, lends a great deal of support for the ILADS paradigm suggesting that long term antibiotics are frequently required for the treatment of established chronic Lyme disease.
In addition, there are published clinical studies supportive of the use of long term antibiotics for chronic, persistent Lyme disease. Studies such as those published by Dr. Donta and Dr. Cameron, are not addressed in the arguments marshaled to support the IDSA guidelines.
The guidelines for Lyme and other diseases should have: reproducibility, flexibility and multidisciplinary input. These are the IDSA's words, not mine. The NIH sponsored studies cited, fail to demonstrate reproducibility. The IDSA guidelines are rigid and fail the flexibility requirement. Certainly, as seen above, the input from other disciplines is clearly lacking.
Moreover, the purpose of the guidelines is to assist patients and practitioners as they make decisions regarding appropriate health care. Again, these are IDSA statements. Patients and physicians who opt to treat Lyme disease outside the IDSA guidelines are well apprised of the IDSA guidelines. In the final analysis, individual decisions regarding treatment should be left to the judgments of the patients and their treating physicians, especially when said patients are fully aware of the differing theories and treatment approaches. This acknowledgment fully comports with the IDSA's own claim that adherence to its guidelines is voluntary.
The science is still uncertain. Only today we learn of a new virulence factor in Lyme bacteria reported by the University of Texas.There is much yet to be learned about this vexing microbe and its associated disease. At this time no Lyme disease guidelines should be considered the final word. For the foreseeable future these guidelines should remain in a constant state of flux and reevaluation.
As the panel is asked to evaluate the current Lyme disease guidelines it will likely be flooded with personal stories and anecdotes. Such stories, although personally moving and emotive, should not confound the important work which needs to be done here. The panel is asked to consider the facts, the science. The panel must remain impartial and assiduously avoid the appearance of partisanship or "rubber stamping" the current guidelines. The findings of this panel may have a tremendous impact on many suffering patients and the dedicated physicians who treat them. And I am sure that panel members in all sincerity desire, that at some future time, as they look back on their work, it will be shown that at this critical juncture, that they were indeed on the right side of history.
Unfortunately, the 2006 Lyme disease guidelines have morphed into something which they are not- a template for the determination of the standard of care regarding the diagnosis and treatment of Lyme disease and tick borne disease. Standards of care are known to vary within different medical communities. Clearly two standards exists. Both ILADS and the IDSA have evidence based guidelines for Lyme disease, which have been vetted be the United States Department of Health and Human Resources and are listed with the National Clearing House of Guidelines.
Lyme is frequently seen as the most controversial and perhaps the most important disease of our times. The IDSA guidelines must be seen in their proper context: they represent the opinions of panel members who were assigned the task of creating said guidelines. Although the guidelines may be based on evidence, ultimately they reflect opinion. It should have been noted that not all panel members were unanimous in their support of the conclusions drawn therein. The existence of strident rejections of guideline conclusions by at least one prominent panel member deserves mention. After all, what is being contested here is the validity of one particular paradigm, supported by the IDSA. In essence, this discussion can be characterized as a war between two diametrically opposed, competing paradigms. To that extent, I believe it is disingenuous when the IDSA either wittingly or unwittingly, promotes the notion that panel members were all in agreement. When a subject is this important, and when the disagreements are so vitriolic, minority opinions become important and should be reported. Similarly, the current requirement that of a quorum of 75% amongst new panel is required to consider revision of the 2006 guidelines is problematic. The IDSA is obligated to report that Lyme disease and the IDSA guidelines remain very controversial. History tells us that paradigms in science and medicine do not easily shift. Not terribly long ago, two scientist were ridiculed by their colleagues for suggesting that peptic ulcer disease was connected to a small bacterium seen in the gastric lining of patients. History later proved that these two pioneers were correct and they were awarded a Nobel prize in 2005.
With this in mind, let us review some of the evidence. The two tier diagnostic test for Lyme disease is simply not valid for the diagnosis of Lyme disease. This test was developed as a surveillance test by the CDC in 1994, not a diagnostic test. It is well known that specific bands 31 and 34 were omitted from the surveillance Western Blot. The United States Congress admonished the CDC to correct the misuse of this test. To date this has not happened. Under oath, CDC representatives, in the Connecticut hearings, reiterated that the test was a surveillance tool and that the diagnosis of Lyme disease was largely clinical. It is an outright embarrassment that the IDSA clings to the incorrect use of the test, stubbornly holding that it is an accurate, evidence based tool for the diagnosis of Lyme disease.
The three NIH sponsored studies looked at a narrow population of Lyme patients: Those who had been previously treated but had persistent symptoms. There are many other groups of patients suffering with Lyme disease who are not included in the cohort which was studied. For example, Some patients have had the disease for years or even decades and yet never sought treatment prior to their initial request for medical care. Many patients are co-infected with Babesia, Ehrlichia and/or Bartonella which may interact with Lyme disease as a syndrome or complex, in ways which have not been studied or established. Some patients are diagnosed with neuroborreliosis showing significant mental status changes with abnormal MRI scans and PET or SPECT scans. Other patients have refractory arthritis as their primary syndrome. These patient types represent the tip of the iceberg. Lyme disease is a multisystem disease associated with protean clinical manifestations. Even if the results of the three NIH studies were in accordance, which they arguably are not, it would be bad science to generalize such results to have wide ranging clinical applicability for many different clinical presentations and patient types suffering with Lyme disease.
The studies were small pilot studies and do not reach the same conclusions. The Klempner study has been widely criticism for a plethora of procedural deficiencies.
Patients with evidence of active Lyme disease- PCR positive were excluded. Test subjects included those who were seropositive as well as those who were seronegative. This is confusing since a key IDSA point is that the standard serological test is accurate. How then was the serogneative-PCR negative test group validated? Assuming the seronegative group did indeed have Lyme disease, how can the two subgroups be combined as a single cohort? The number of study subjects was smaller than the requisite number required by the study design. There is no agreed upon the definition of what constitutes long term therapy. For that matter, the correct choice of antimicrobial therapy has not been agreed upon or has the manner in which it should be administered. For example, perhaps the treatment group would have responded more favorably if the 2 months of oral doxycyline preceded the 30 days of IV Rocephin? The study was vary narrow in its design and outcome measurements. The use of these results to support far reaching conclusions, as has been frequently done, would seem to be bad science at best.
The Krupp study was a rehash of the Klempner trial. In this case patients were treated for 28 days with Rocephin. The results were not entirely negative. Patients with severe fatigue were shown to experience improvement. It was not known what outcomes may have been found if the study was extended to 8 or 12 weeks.
The results of the Fallon study were not available at the time the 2006 guidelines were developed. Here a group of individuals with severe neuroborreliois where shown to have cognitive improvements after 10 weeks of Rocephin. That fact that the improvements were not sustained is not evidence that the therapy did not work. It could be easily construed as evidence that the therapy was inadequate. For example, it is not know whether the cognitive improvements would have been sustained if the IV therapy had been continued- or if Rocephin therapy had been followed by continued oral antibiotic treatment for some period of time.
The guidelines are supposed to include multidisciplinary inputs. Where are the contributions of molecular biologists, microbiologists, immunologists and many others? Borrelia burdorferi has been demonstrated to persist in human and animal hosts in the face of extensive exposure to antimicrobials. Borrelia burdorferi has more plasmids than any other known bacteria. It has numerous mechanisms for evading eradication by the immune system and antibiotics. It has the ability to shift its antigens as has been amply demonstrated. It has the ability to live and proliferate in various protected niches. It has the ability to change its morphology and shift into intracellular L-forms and cystic forms. It is known that intracellular bacteria are not amenable to acquired humoral responses and that immunological defenses are mediated by innate immune responses. These innate responses, as has been shown with numerous other intracellular bacteria, frequently fail to completely eradicate the offending bacteria. Bb has the demonstrated ability to readily cross the blood brain barrier causing persistent infection and inflammation. The immune privileged brain allows a protective niche for long term survival. A large repertoire of well documented basic science, published in respected, peer reviewed journals describing the morphology and complex biological activity of Bb, both in vitro and in vivo, lends a great deal of support for the ILADS paradigm suggesting that long term antibiotics are frequently required for the treatment of established chronic Lyme disease.
In addition, there are published clinical studies supportive of the use of long term antibiotics for chronic, persistent Lyme disease. Studies such as those published by Dr. Donta and Dr. Cameron, are not addressed in the arguments marshaled to support the IDSA guidelines.
The guidelines for Lyme and other diseases should have: reproducibility, flexibility and multidisciplinary input. These are the IDSA's words, not mine. The NIH sponsored studies cited, fail to demonstrate reproducibility. The IDSA guidelines are rigid and fail the flexibility requirement. Certainly, as seen above, the input from other disciplines is clearly lacking.
Moreover, the purpose of the guidelines is to assist patients and practitioners as they make decisions regarding appropriate health care. Again, these are IDSA statements. Patients and physicians who opt to treat Lyme disease outside the IDSA guidelines are well apprised of the IDSA guidelines. In the final analysis, individual decisions regarding treatment should be left to the judgments of the patients and their treating physicians, especially when said patients are fully aware of the differing theories and treatment approaches. This acknowledgment fully comports with the IDSA's own claim that adherence to its guidelines is voluntary.
The science is still uncertain. Only today we learn of a new virulence factor in Lyme bacteria reported by the University of Texas.There is much yet to be learned about this vexing microbe and its associated disease. At this time no Lyme disease guidelines should be considered the final word. For the foreseeable future these guidelines should remain in a constant state of flux and reevaluation.
As the panel is asked to evaluate the current Lyme disease guidelines it will likely be flooded with personal stories and anecdotes. Such stories, although personally moving and emotive, should not confound the important work which needs to be done here. The panel is asked to consider the facts, the science. The panel must remain impartial and assiduously avoid the appearance of partisanship or "rubber stamping" the current guidelines. The findings of this panel may have a tremendous impact on many suffering patients and the dedicated physicians who treat them. And I am sure that panel members in all sincerity desire, that at some future time, as they look back on their work, it will be shown that at this critical juncture, that they were indeed on the right side of history.
Friday, March 6, 2009
IDSA and bad science
The IDSA is accepting comments and letters as they prepare for their open hearing on Lyme disease and the IDSA guidelines this April in Washington D.C. I am sure many are aware of this. At this time I am preparing a model letter which I plan to publish on this BLOG.
One glaring, critical flaw in the IDSA logic is staring me in the face, so in advance of my letter, I have decided to share this one point with my readers.
The IDSA claims that the controlled trials have shown that patients with chronic Lyme or post Lyme do not benefit from prolonged use of antibiotics. They are of course referring to the 3 NIH sponsored studies: Klempner, Krupp and Fallon.
All three studies were designed to look at patients with an established diagnosis of LD who were first treated with IDSA approved courses of antibiotics and yet still complained of various symptoms.
Most of the patients I see with chronic Lyme developed symptoms over a period of years and have never been treated with the IDSA approved Lyme disease regimens or any antibiotics for that matter. These patients are not the subset studied in the 3 NIH sponsored trials.
These studies consider only a small subset of patients identified as having chronic Lyme or post Lyme. The generalization of the findings to all groups of patients with Lyme disease is bad science at the very least.
If one were to study patients who had been previously treated for primary syphilis and then apply the results to heretofore untreated patients with disseminated tertiary syphilis, all would agree that this would be preposterous. In the case of Lyme disease the rules of logic and science apparently do not apply. Not only is the illogical non-science accepted by many well known physicians, but the New England Journal of Medicine agreed to publish an editorial predicated on such nonsensical thinking. One can only conclude that a determined group of individuals, having decided a priori what a particular study would show, twisted, massaged and manipulated the limited data to fit into the "Procrustean bed" of their forgone conclusions. This is not science. Whatever it may be- I have no name for it.
Unfortunately as absurd as this all may seen, the consequences of these machinations has had, and continues to have, a devastating impact on so many suffering patients and the physicians who treat them.
This is not just bad science- it is outside the pale.
One glaring, critical flaw in the IDSA logic is staring me in the face, so in advance of my letter, I have decided to share this one point with my readers.
The IDSA claims that the controlled trials have shown that patients with chronic Lyme or post Lyme do not benefit from prolonged use of antibiotics. They are of course referring to the 3 NIH sponsored studies: Klempner, Krupp and Fallon.
All three studies were designed to look at patients with an established diagnosis of LD who were first treated with IDSA approved courses of antibiotics and yet still complained of various symptoms.
Most of the patients I see with chronic Lyme developed symptoms over a period of years and have never been treated with the IDSA approved Lyme disease regimens or any antibiotics for that matter. These patients are not the subset studied in the 3 NIH sponsored trials.
These studies consider only a small subset of patients identified as having chronic Lyme or post Lyme. The generalization of the findings to all groups of patients with Lyme disease is bad science at the very least.
If one were to study patients who had been previously treated for primary syphilis and then apply the results to heretofore untreated patients with disseminated tertiary syphilis, all would agree that this would be preposterous. In the case of Lyme disease the rules of logic and science apparently do not apply. Not only is the illogical non-science accepted by many well known physicians, but the New England Journal of Medicine agreed to publish an editorial predicated on such nonsensical thinking. One can only conclude that a determined group of individuals, having decided a priori what a particular study would show, twisted, massaged and manipulated the limited data to fit into the "Procrustean bed" of their forgone conclusions. This is not science. Whatever it may be- I have no name for it.
Unfortunately as absurd as this all may seen, the consequences of these machinations has had, and continues to have, a devastating impact on so many suffering patients and the physicians who treat them.
This is not just bad science- it is outside the pale.
Tuesday, March 3, 2009
Chest pain in a young woman- should be an easy one
It looked like an easy one for a change. I picked up the chart of my new patient- a 36 year old woman complaining of chest pain. She appeared to be a fit healthy woman in no obvious stress. Immediately, I began considering the differential diagnosis of chest pain in a young woman. The usual suspects quickly came to mind: chest wall strain, costochondritis- inflammation of the cartilage where the ribs join the sternum, a trapped gas bubble, stress/anxiety, lung infection- especially pleurisy, possible mitral valve prolapse, acid reflux disease and a few others. Coronary heart disease seemed quite unlikely. Pericarditis was near the bottom of my list.
I then took the patient's history. The pain had been present for two months, but recently- over the past one week, it had become more severe. It was constant and was located in the left chest area. It was not pleuritic (it did not increase with respiration). It did not radiate. It was not associated with sweating or shortness of breath. She did not have heartburn. The pain was not reproducible with pressure applied to the chest wall or with movements of her body. There was no history of trauma. These are standard doctor questions in the evaluation of chest pain.
What made the pain better or worse? The pain improved with aspirin and with leaning over. Interesting.
Oddly enough she complained of severe fatigue. She denied a history of a recent respiratory infection or viral syndrome.
And then oddly enough she complained of occasional night sweats over a period of two months corresponding to the time frame of the chest pain. I filed this away in my head.
Her history and exam were unremarkable. She had a mild systolic heart murmur but I thought it was within the normal range.
To be complete I performed an EKG: normal. I considered the fact that the pain decreased when she bent over. I recalled that pericarditis associated chest pain can improve with a change in position. Frequently bending forward makes it worse rather than better.
I have on site cardiac echo. To be thorough, I performed an echocardiogram.
The findings were surprising. There was fluid around the heart in the pericardial sack. This is compatible with the diagnosis of pericarditis. Frequently preicarditis in an otherwise healthy young woman is due to a viral infection and is self limiting. Of course there is a long list of disorders which may cause pericarditis, including: lupus and other autoimmune syndromes, tuberculosis, HIV, fungal infections, parasitic infections, bacterial infections, kidney disease, and unusual cardiac disorders. I also know that pericarditis can be a manifestation of Lyme disease. I ordered an anti inflammatory drug, Indocin assuming she had viral pericarditis.
As we were finishing up the visit I asked another question, as an after thought: Have you had any tick bites?
She answered: Yes, three years ago, it was a tiny tick and I could barely see it. I think there was a rash as well.
Pericarditis, fatigue, night sweats and a tick bite: I had to connect the dots- It looks like Lyme yet again.
I then took the patient's history. The pain had been present for two months, but recently- over the past one week, it had become more severe. It was constant and was located in the left chest area. It was not pleuritic (it did not increase with respiration). It did not radiate. It was not associated with sweating or shortness of breath. She did not have heartburn. The pain was not reproducible with pressure applied to the chest wall or with movements of her body. There was no history of trauma. These are standard doctor questions in the evaluation of chest pain.
What made the pain better or worse? The pain improved with aspirin and with leaning over. Interesting.
Oddly enough she complained of severe fatigue. She denied a history of a recent respiratory infection or viral syndrome.
And then oddly enough she complained of occasional night sweats over a period of two months corresponding to the time frame of the chest pain. I filed this away in my head.
Her history and exam were unremarkable. She had a mild systolic heart murmur but I thought it was within the normal range.
To be complete I performed an EKG: normal. I considered the fact that the pain decreased when she bent over. I recalled that pericarditis associated chest pain can improve with a change in position. Frequently bending forward makes it worse rather than better.
I have on site cardiac echo. To be thorough, I performed an echocardiogram.
The findings were surprising. There was fluid around the heart in the pericardial sack. This is compatible with the diagnosis of pericarditis. Frequently preicarditis in an otherwise healthy young woman is due to a viral infection and is self limiting. Of course there is a long list of disorders which may cause pericarditis, including: lupus and other autoimmune syndromes, tuberculosis, HIV, fungal infections, parasitic infections, bacterial infections, kidney disease, and unusual cardiac disorders. I also know that pericarditis can be a manifestation of Lyme disease. I ordered an anti inflammatory drug, Indocin assuming she had viral pericarditis.
As we were finishing up the visit I asked another question, as an after thought: Have you had any tick bites?
She answered: Yes, three years ago, it was a tiny tick and I could barely see it. I think there was a rash as well.
Pericarditis, fatigue, night sweats and a tick bite: I had to connect the dots- It looks like Lyme yet again.
Chronic Lyme disease- The debate- Rephrased
Lyme disease symptoms can persist after IDSA recommended antibiotic therapy.
The argument that this represents a post-infection syndrome rather than a continuing infection has become the crux of the debate as framed by the IDSA.
This disagreement is really a sidebar. Let us put this particular discussion aside for the moment and look at things from a different perspective.
Across the board, physicians agree that late disseminated Lyme disease is a real entity. The IDSA argument claims that MOST Lyme patients present with an acute easily discernible syndrome. The IDSA would agree that some patients with well documented Lyme disease present differently.
Let's look at a comparison with syphilis once more. Syphilis starts with a painless lesion in the genitalia, called a chancre- the acute syndrome. Many patients with syphilis can recall no history of such an exposure. For decades syphilis has been called the great imitator. It has the ability to disseminate widely after a quiescent stage and mimic many other medical disorders. We know that syphilis has 3 stages. In the second stage, years or decades may pass without the appearance of symptoms. When syphilis finally shows itself, stage 3, we can see a devastating, multi-system disease. We know that late syphilis of the brain and central nervous is frequently associated with dementia and death and that no satisfactory therapy is reported in current medical literature/guidelines.
Lyme is now referred to as the new great imitator. Does initial Lyme infection always cause features consistent with an acute case? Clearly the answer is no. The most common vector is the nymph forms of the hard body Ixodes ticks. These tiny arthropods are the size of a poppy seed. They are stealthy vectors, and more often than not are unobserved by their victims. Many patient do not develop the tell tale rash. There is some disagreement about the frequency of EM rashes, but there is no dispute that they are absent in some or many patients. Bites frequently occur in areas which are hidden, for example,the back of the neck. If the classic rash does occur it can easily be missed by the patient. Some patient, newly infected with Bb develop acute flu like symptoms; but as we have seen, such symptoms are frequently dismissed as viral.
Lyme may enter into a prolonged asymptomatic phase, just like syphilis. These latent spirochetes can quietly disseminate. Symptomatic disease may not appear for many months or even years. A great imitator like Lyme disease can cause a protean array of symptoms and syndromes. This may be a point of disagreement between ILADS and the IDSA. This dispute can also be put aside for the moment. There is no debate that Bb is very neurotropic: It has a known proclivity for infecting both the brain and nervous system.
Penicillin treatments for neurosyphilis are known to be unsatisfactory. The treatment of established spirochete infection in the brain is known to be very difficult.
Many late stage patients with Lyme disease present with neuroborreliosis. This is clearly established and accepted by all groups familiar with the disease, irrespective of their IDSA/ILADS bias. Neuroborreliosis patients have concrete, object findings: Alterations of mental status, abnormal MRIs and abnormal SPECT scan. Forgive my verbiage- It is "no brainer".
Fallon has shown: patients with neuroborreliosis improve with IV Rocephin. The improvements regress with cessation of therapy. The improvements return when therapy is started again. What does this tell us??
I don't think you have to be a physician (or a rocket scientist) to imagine what might be occurring here. The antibiotics temporarily keep the infection at bay- patients improve; antibiotics are stopped- patients worsen- because the offending germs have not been eradicated. Fallon did not continue patients on oral antibiotics when the IV Rocephin was stopped. Many LLMDS, myself included have found that this approach frequently maintains the improvements gained from Rocephin. This begs the question: Why is there a controversy- at least regarding documented neuroborreliosis.
If something is working why stop therapy ? Why is this considered good medicine?
The argument that this represents a post-infection syndrome rather than a continuing infection has become the crux of the debate as framed by the IDSA.
This disagreement is really a sidebar. Let us put this particular discussion aside for the moment and look at things from a different perspective.
Across the board, physicians agree that late disseminated Lyme disease is a real entity. The IDSA argument claims that MOST Lyme patients present with an acute easily discernible syndrome. The IDSA would agree that some patients with well documented Lyme disease present differently.
Let's look at a comparison with syphilis once more. Syphilis starts with a painless lesion in the genitalia, called a chancre- the acute syndrome. Many patients with syphilis can recall no history of such an exposure. For decades syphilis has been called the great imitator. It has the ability to disseminate widely after a quiescent stage and mimic many other medical disorders. We know that syphilis has 3 stages. In the second stage, years or decades may pass without the appearance of symptoms. When syphilis finally shows itself, stage 3, we can see a devastating, multi-system disease. We know that late syphilis of the brain and central nervous is frequently associated with dementia and death and that no satisfactory therapy is reported in current medical literature/guidelines.
Lyme is now referred to as the new great imitator. Does initial Lyme infection always cause features consistent with an acute case? Clearly the answer is no. The most common vector is the nymph forms of the hard body Ixodes ticks. These tiny arthropods are the size of a poppy seed. They are stealthy vectors, and more often than not are unobserved by their victims. Many patient do not develop the tell tale rash. There is some disagreement about the frequency of EM rashes, but there is no dispute that they are absent in some or many patients. Bites frequently occur in areas which are hidden, for example,the back of the neck. If the classic rash does occur it can easily be missed by the patient. Some patient, newly infected with Bb develop acute flu like symptoms; but as we have seen, such symptoms are frequently dismissed as viral.
Lyme may enter into a prolonged asymptomatic phase, just like syphilis. These latent spirochetes can quietly disseminate. Symptomatic disease may not appear for many months or even years. A great imitator like Lyme disease can cause a protean array of symptoms and syndromes. This may be a point of disagreement between ILADS and the IDSA. This dispute can also be put aside for the moment. There is no debate that Bb is very neurotropic: It has a known proclivity for infecting both the brain and nervous system.
Penicillin treatments for neurosyphilis are known to be unsatisfactory. The treatment of established spirochete infection in the brain is known to be very difficult.
Many late stage patients with Lyme disease present with neuroborreliosis. This is clearly established and accepted by all groups familiar with the disease, irrespective of their IDSA/ILADS bias. Neuroborreliosis patients have concrete, object findings: Alterations of mental status, abnormal MRIs and abnormal SPECT scan. Forgive my verbiage- It is "no brainer".
Fallon has shown: patients with neuroborreliosis improve with IV Rocephin. The improvements regress with cessation of therapy. The improvements return when therapy is started again. What does this tell us??
I don't think you have to be a physician (or a rocket scientist) to imagine what might be occurring here. The antibiotics temporarily keep the infection at bay- patients improve; antibiotics are stopped- patients worsen- because the offending germs have not been eradicated. Fallon did not continue patients on oral antibiotics when the IV Rocephin was stopped. Many LLMDS, myself included have found that this approach frequently maintains the improvements gained from Rocephin. This begs the question: Why is there a controversy- at least regarding documented neuroborreliosis.
If something is working why stop therapy ? Why is this considered good medicine?
Monday, March 2, 2009
Alan G. Barbour, M.D: In his own words
Dr. Barbour wrote a wonderful little book intended for the lay public in 1996.
The Book is titled: Lyme Disease, The Cause, the Cure, the Controversy.
The book is full of interesting and sometimes quite detailed information. Dr. Barbour does a wonderful job of explaining the ELISA test, its methodology and "Pitfalls."
The sensitivity and specificity of the test is claimed to be 94 to 98%. But the predictive value of the test is consider "much lower," when the history and physical show that the chance of having Lyme disease is low. This is a critical point. First of all, why would someone perform the test if the likelihood of Lyme disease was low?
The sensitivity and specificity numbers are based on what LLMDS would call a narrow notion of the symptoms and signs associated with Lyme disease. The thinking at that time, which has persisted to this day in IDSA quarters, is that Lyme disease presents with certain well defined syndromes. These include the EM rash,inflammatory arthritis- typically a large joint, Bell's Palsy, acute meningitis and typical cardiac disease such as atrioventricular block. In this "old" thinking, symptoms such as fatigue, generalized pains and brain fog are not part of the equation. These are the classic symptoms that most LLMDS consider typical of Lyme disease.
The ELISA test gives a reaction on a scale. He admits (pages 96,97) that the positive cutoff point is set by "someone, or more likely a committee." This means that a group of experts picked a cutoff point for a positive reaction based on the best information available to the group at the time.
Here are his important words: "How is the cutoff point set? Selecting a cutoff point would be simple if people without Lyme disease showed no reactivity in the assay...But this is not what has been found. On the contrary, a substantial number of healthy people or 'negative controls,' as they are known, have had detectable antibodies that bound to spirochete parts." ...These people seldom had titers or color values which were as high as those of Lyme disease patients, but the two groups did overlap. There was no value below which all control sera fell and which all Lyme disease sera fell."
What he is clearly saying is that patients without Lyme disease and those with Lyme disease could react similarly on the ELISA assay. The people without "Lyme disease" were a healthy control group. Remember, his definition of Lyme disease was quite narrow. Control subjects with fatigue and brain fog could have been included in the "healthy" control group.
He cites 3 reasons for what he considers false positive results: Infection with something that causes cross reactivity, like syphilis; someone could have "sticky" antibodies, as seen in autoimmune disorders; or test subjects may have actually been exposed to Lyme disease in the past. Question: How can previous exposure to Lyme disease be considered a false positive? The science now informs us that Lyme is a persistent infection once it becomes established in the host.
It seems to me that it is relatively easy to rule out the first two items. therefore, a positive ELISA test should indicate exposure to Lyme disease.
As explained above, the cutoff for a positive ELISA was set high based on prevailing beliefs. If a patient has a positive ELISA it would seem to prove Bb exposure.
According to CDC/IDSA rules the positive ELISA must be followed by a Western Blot. Based on what is described above this does not seem reasonable. The WB bands reported are based on the CDC surveillance case definition and have not been validated as a diagnostic test. We know that critical bands such as the 31 and 34 bands have been omitted AND that only 3 IgM bands are reported.
Based on what logic can this test be used to confirm a positive ELISA test? The ELISA tests we are told have many false positives. Dr. Barbour, who was there when the ELISA test for Lyme disease was developed seems to be saying, that in the main, false positive ELISA results indicate previous exposure to Lyme disease.
To make matters worse, labs no longer report the value of the ELISA index. If a physician were to reasonably infer that the cut off for a positive test was set to high, the physician is no longer afforded the ability to apply his clinical judgment to assess the significance of a particular ELISA value.
On page 170, Dr. Barbour discusses the controversy of post-Lyme disease versus chronic Lyme disease. He does not deny that chronic Lyme disease exists. He relates this to "late infection." He states: "The difference between the two disorders is that most patients with late infection, still respond, at least partially, to antibiotic therapy, while patients with the post-infection syndrome usually do not."
Dr. Barbour's writing here would appear to support the ILADS approach: "If a patient improves with continued antibiotic therapy, the patient has chronic Lyme disease."
After all, is this not the basic issue upon which ILADS and IDSA disagree? He states that studies sponsored by the NIH should further clarify the issue. Three studies have now been done, yet, the waters remain muddy.
To be fair to Dr. Barbour, he discounts the correlation of "atypical symptoms": fatigue, generalized aches and pains, sleep problems, brain fog and others with Lyme disease. The paradigm described in the book states that such symptoms are likely not due to chronic Lyme disease. Although, he leaves open the door for post-Lyme correlating with such symptoms.
He wrote that other infections such as HIV should be considered. He wrote that patients may have chronic fatigue syndrome, fibromyalgia or a psychiatric disorder.
He does have an interesting chart in which he compares the features of Post-Lyme disease with Fibromyalgia and Chronic fatigue syndrome. He considers that the following symptoms may be found in all three disorders: Fatigue unrelieved by rest, activity less than 50% normal, unrefreshing sleep, difficulty concentrating, musculoskeletal pain and headache. If current science shows that Lyme persists in the host then would it not be reasonable to at least consider the possibility that post-Lyme really is chronic Lyme?
He further posits the main IDSA argument: Symptoms are subjective- there are no objective measurements which prove that Lyme is the cause for chronic symptoms. At any rate it is assumed that persistent symptoms are largely the product of a post-infection syndrome.
He posits that Lyme is not the cause of neurological disorder such as MS and ALS.
He says that Lyme is not a cause of autoimmune disease such as RA and SLE. He does admit that it has been postulated that infections may trigger such disorders but states there is no objective evidence that treatment is effective.
I believe that Dr. Barbour's statements reflect the ongoing position posited by the CDC and ILADS. Perhaps some updating of these views should be considered.
We certainly know that Lyme disease, if not the cause of MS and ALS, can mimic these disease states.
We know that patients with "autoimmune," inflammatory arthritis have shown positive PCR tests of synovial fluid and tissues for Lyme and Mycoplasms. We know that the same patients have improved with antibiotic therapies. Some patients show positive tests for RA and SLE which improve with antibiotic therapy.
Patients DO GET BETTER WITH CONTINUED ANTIBIOTICS. Shouldn't chronic Lyme rather than post-Lyme be considered based on Dr. Barbour's own comments?
There IS objective evidence in chronic Lyme patients. They have fevers and chills. They have Herxheimer reactions with antibiotic therapy and then seroconvert on ELISA and Western Blot tests. They test positive for co-infections. They have abnormal physical exams which revert to normal after therapy. They have abnormal lab studies, outside of Lyme per say. They have organisms in the blood which have yet to be identified. They have low CD57 counts. They have changes in vitamin D levels. They have changes in vitamin B12 and folic acid. They have abnormalities seen in the- CBC, sed rate, CRP, comlement levels and other lab parameters. They have abnormal MRI and SPECT brain scans.
There is at least one NIH sponsored clinical study which supports the existence of chronic Lyme disease. The two other studies are controversial and can be interpreted in different ways.
This book is full of interesting facts and contradictions. It reflects a mainstream medical position which remains unchanged for years, and which continues to ignore information which undercuts its primary tenants.
The ELISA and Western Blot tests are clearly flawed, as evinced in this book, yet the CDC's has solidified its position regarding the two tiered Lyme test. On what basis?
An oft quoted adage in medicine is: "You only diagnose that which you know."
One must always keep an open mind because in a field like medicine, there will always be much that one does not know.
The Book is titled: Lyme Disease, The Cause, the Cure, the Controversy.
The book is full of interesting and sometimes quite detailed information. Dr. Barbour does a wonderful job of explaining the ELISA test, its methodology and "Pitfalls."
The sensitivity and specificity of the test is claimed to be 94 to 98%. But the predictive value of the test is consider "much lower," when the history and physical show that the chance of having Lyme disease is low. This is a critical point. First of all, why would someone perform the test if the likelihood of Lyme disease was low?
The sensitivity and specificity numbers are based on what LLMDS would call a narrow notion of the symptoms and signs associated with Lyme disease. The thinking at that time, which has persisted to this day in IDSA quarters, is that Lyme disease presents with certain well defined syndromes. These include the EM rash,inflammatory arthritis- typically a large joint, Bell's Palsy, acute meningitis and typical cardiac disease such as atrioventricular block. In this "old" thinking, symptoms such as fatigue, generalized pains and brain fog are not part of the equation. These are the classic symptoms that most LLMDS consider typical of Lyme disease.
The ELISA test gives a reaction on a scale. He admits (pages 96,97) that the positive cutoff point is set by "someone, or more likely a committee." This means that a group of experts picked a cutoff point for a positive reaction based on the best information available to the group at the time.
Here are his important words: "How is the cutoff point set? Selecting a cutoff point would be simple if people without Lyme disease showed no reactivity in the assay...But this is not what has been found. On the contrary, a substantial number of healthy people or 'negative controls,' as they are known, have had detectable antibodies that bound to spirochete parts." ...These people seldom had titers or color values which were as high as those of Lyme disease patients, but the two groups did overlap. There was no value below which all control sera fell and which all Lyme disease sera fell."
What he is clearly saying is that patients without Lyme disease and those with Lyme disease could react similarly on the ELISA assay. The people without "Lyme disease" were a healthy control group. Remember, his definition of Lyme disease was quite narrow. Control subjects with fatigue and brain fog could have been included in the "healthy" control group.
He cites 3 reasons for what he considers false positive results: Infection with something that causes cross reactivity, like syphilis; someone could have "sticky" antibodies, as seen in autoimmune disorders; or test subjects may have actually been exposed to Lyme disease in the past. Question: How can previous exposure to Lyme disease be considered a false positive? The science now informs us that Lyme is a persistent infection once it becomes established in the host.
It seems to me that it is relatively easy to rule out the first two items. therefore, a positive ELISA test should indicate exposure to Lyme disease.
As explained above, the cutoff for a positive ELISA was set high based on prevailing beliefs. If a patient has a positive ELISA it would seem to prove Bb exposure.
According to CDC/IDSA rules the positive ELISA must be followed by a Western Blot. Based on what is described above this does not seem reasonable. The WB bands reported are based on the CDC surveillance case definition and have not been validated as a diagnostic test. We know that critical bands such as the 31 and 34 bands have been omitted AND that only 3 IgM bands are reported.
Based on what logic can this test be used to confirm a positive ELISA test? The ELISA tests we are told have many false positives. Dr. Barbour, who was there when the ELISA test for Lyme disease was developed seems to be saying, that in the main, false positive ELISA results indicate previous exposure to Lyme disease.
To make matters worse, labs no longer report the value of the ELISA index. If a physician were to reasonably infer that the cut off for a positive test was set to high, the physician is no longer afforded the ability to apply his clinical judgment to assess the significance of a particular ELISA value.
On page 170, Dr. Barbour discusses the controversy of post-Lyme disease versus chronic Lyme disease. He does not deny that chronic Lyme disease exists. He relates this to "late infection." He states: "The difference between the two disorders is that most patients with late infection, still respond, at least partially, to antibiotic therapy, while patients with the post-infection syndrome usually do not."
Dr. Barbour's writing here would appear to support the ILADS approach: "If a patient improves with continued antibiotic therapy, the patient has chronic Lyme disease."
After all, is this not the basic issue upon which ILADS and IDSA disagree? He states that studies sponsored by the NIH should further clarify the issue. Three studies have now been done, yet, the waters remain muddy.
To be fair to Dr. Barbour, he discounts the correlation of "atypical symptoms": fatigue, generalized aches and pains, sleep problems, brain fog and others with Lyme disease. The paradigm described in the book states that such symptoms are likely not due to chronic Lyme disease. Although, he leaves open the door for post-Lyme correlating with such symptoms.
He wrote that other infections such as HIV should be considered. He wrote that patients may have chronic fatigue syndrome, fibromyalgia or a psychiatric disorder.
He does have an interesting chart in which he compares the features of Post-Lyme disease with Fibromyalgia and Chronic fatigue syndrome. He considers that the following symptoms may be found in all three disorders: Fatigue unrelieved by rest, activity less than 50% normal, unrefreshing sleep, difficulty concentrating, musculoskeletal pain and headache. If current science shows that Lyme persists in the host then would it not be reasonable to at least consider the possibility that post-Lyme really is chronic Lyme?
He further posits the main IDSA argument: Symptoms are subjective- there are no objective measurements which prove that Lyme is the cause for chronic symptoms. At any rate it is assumed that persistent symptoms are largely the product of a post-infection syndrome.
He posits that Lyme is not the cause of neurological disorder such as MS and ALS.
He says that Lyme is not a cause of autoimmune disease such as RA and SLE. He does admit that it has been postulated that infections may trigger such disorders but states there is no objective evidence that treatment is effective.
I believe that Dr. Barbour's statements reflect the ongoing position posited by the CDC and ILADS. Perhaps some updating of these views should be considered.
We certainly know that Lyme disease, if not the cause of MS and ALS, can mimic these disease states.
We know that patients with "autoimmune," inflammatory arthritis have shown positive PCR tests of synovial fluid and tissues for Lyme and Mycoplasms. We know that the same patients have improved with antibiotic therapies. Some patients show positive tests for RA and SLE which improve with antibiotic therapy.
Patients DO GET BETTER WITH CONTINUED ANTIBIOTICS. Shouldn't chronic Lyme rather than post-Lyme be considered based on Dr. Barbour's own comments?
There IS objective evidence in chronic Lyme patients. They have fevers and chills. They have Herxheimer reactions with antibiotic therapy and then seroconvert on ELISA and Western Blot tests. They test positive for co-infections. They have abnormal physical exams which revert to normal after therapy. They have abnormal lab studies, outside of Lyme per say. They have organisms in the blood which have yet to be identified. They have low CD57 counts. They have changes in vitamin D levels. They have changes in vitamin B12 and folic acid. They have abnormalities seen in the- CBC, sed rate, CRP, comlement levels and other lab parameters. They have abnormal MRI and SPECT brain scans.
There is at least one NIH sponsored clinical study which supports the existence of chronic Lyme disease. The two other studies are controversial and can be interpreted in different ways.
This book is full of interesting facts and contradictions. It reflects a mainstream medical position which remains unchanged for years, and which continues to ignore information which undercuts its primary tenants.
The ELISA and Western Blot tests are clearly flawed, as evinced in this book, yet the CDC's has solidified its position regarding the two tiered Lyme test. On what basis?
An oft quoted adage in medicine is: "You only diagnose that which you know."
One must always keep an open mind because in a field like medicine, there will always be much that one does not know.
The amazing Lyme WB 100 Kd band???
Clongen labs reports the whole spectrum of Lyme WB bands. The Bands as seen on a Western Blot strip are shown heaviest to lightness. Other labs that I am familiar with report the heaviest band as 83-93. Lyme WB strips from Clongen show "all the bands"; there are more than 14. The Clongen strips frequently show reactivity at 100 Kd band which exceeds the control response. I asked Dr. K what this 100 Kd band was. He did not know. He just presents the data. Intrigued, I did a little research. I have found nothing in human literature. But I did find something.
Of particular interest is a paper called: Lyme-Disease- "a consensus statement"
This paper is talking about canine, not human Lyme disease.
The piece was written in 2005. It comes from a German lab- LABOKLIN.
The bands discussed in the paper are for the most part quite familiar. They include:
the 24Kd band (23-25), the 31Kd band, the 39Kd band and the 41Kd band.
The article notes that the 41 band is associated with flagellin protein and that the 31 band is associated with OSPA. Sound familiar?
They paper claims that the best Lyme WB band is the 100 Kd band. Although it is seen only in late disease, the authors state "...there is not known cross reaction and (it) is therefore pathognomonic." The means that reactivity at the 100 Kd WB bands confirms Lyme exposure with 100% accuracy. If the same holds true in humans this may be incredibly significant!
Comments please!
Of particular interest is a paper called: Lyme-Disease- "a consensus statement"
This paper is talking about canine, not human Lyme disease.
The piece was written in 2005. It comes from a German lab- LABOKLIN.
The bands discussed in the paper are for the most part quite familiar. They include:
the 24Kd band (23-25), the 31Kd band, the 39Kd band and the 41Kd band.
The article notes that the 41 band is associated with flagellin protein and that the 31 band is associated with OSPA. Sound familiar?
They paper claims that the best Lyme WB band is the 100 Kd band. Although it is seen only in late disease, the authors state "...there is not known cross reaction and (it) is therefore pathognomonic." The means that reactivity at the 100 Kd WB bands confirms Lyme exposure with 100% accuracy. If the same holds true in humans this may be incredibly significant!
Comments please!
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