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.