Dr. Weinstein: Was not a member of the original 2006 guidelines panel, but I was a consultant and reviewed draft copy before it went to press. I have no conflicts, I have no patents [Phonetic] [0:00:15], no relationships with laboratory, or vaccine companies. And unfortunately, I have no extra real funding at present for Lyme disease research. So I would like to thank you and the idea, say for the opportunity to present my opinion to you regarding chronic symptoms of Lyme disease, post Lyme disease syndrome, post Lyme disease symptoms as discussed in the 2006 guidelines. And the title of this talk is chronic symptoms… by the way I have no power point presentations, so you have to look at me. Chronic symptoms of Lyme disease, if not chronic Lyme disease then what is the diagnosis? So I was a clinical and academic rheumatologist University of Connecticut, when Allen first described Lyme arthritis. And then in 1985 I moved to New York Medical College in Westchester County where Lyme disease is of course highly endemic. And I developed an interest in its diagnosis and treatment, especially the musculoskeletal features. Over the years I have seen numerous patients with Lyme disease in all it’s stages developed and ran a diagnostic laboratory which included in house Lyme disease testing served on a number of communities and panels with some of you concerned with laboratory diagnosis of Lyme disease and have collaborated in a number of research studies related to it’s diagnosis and it’s treatment. The focus of my interest as a rheumatologist has been the musculoskeletal manifestations associated with Lyme disease.

Initially, I believed that Lyme disease was eminently treatable in it’s early and even later stages and that most if not all patients would become asymptomatic with proper antibiotic therapy. We certainly understood that occasionally a single course of antibiotics might be insufficient in eradicating the organism, especially, in patients with Lyme arthritis and we also knew that some patients would develop as Allen has mentioned chronic Lyme arthritis with persistent or recurrent possibly autoimmune inflammation of a previously infected joint. However, in both these instances the symptoms were accompanied by objective findings of knee inflammation and could be treated by another course of antibiotics for the former and by synovectomy for the later. However, I remained skeptical that other musculoskeletal problems were induced by Lyme disease. I was disavowed of that belief by my faculty colleagues, who noted that there were patients who remained symptomatic, despite one or more courses of antibiotics and that these symptoms could be disabling and persist for months or even years. We were spured on by the patients that we were seeing in our practices with these complaints, mainly arthralgia and fatigue without objective physical findings, seeming to improve temporarily with oral or intravenous antibiotics to conduct a retrospective observation study on patients who had been diagnosed and treated for Lyme disease reported to the Westchester County Department of Health.

Now admittedly, this study had major flaws. It was subject to the biases of a retrospective study. There was no control group in Lyme disease diagnosis by laboratory testing was not very accurate at that time. However, among cohered of 215 patients were some who clearly have a history of objective findings of reinfection or relapse to late Lyme disease or who had incomplete recovery with objective structural change. However, there were many patients who had chronic complaints of arthralgia and fatigue

without objective findings that had begun concomitantly with or soon after early or late Lyme disease. These patients had improved from their original acute Lyme disease illness and the persistent symptoms did not collaborate with a history of reinfection or with persistent sera positivity by ELISA testing. So this prompted us to speculate that this was a post infectious syndrome, rather than caused by Borrelia infection, but we had no direct proof of such. Since then as you know there hasn’t been much investment of time and of energy and of funding, into tempting to determine whether objective evidence of chronic Borrelia infection is the cause of these symptoms and whether repeated or prolonged courses of antibiotic treatment has a durable affect in eradicating them. Sadly, solid and robust scientific evidence does not support this theory or this treatment.

So if not due to Borrelia infection what then is the cause of these symptoms and how are these unfortunate patients to be treated? This post Lyme disease syndrome has many features, but prototypically it is a pain syndrome characterized by arthralgias and myalgias without joint swelling or objective muscle weakness, profound fatigue, and subjective cognitive difficulties. The symptoms may wax and wean overtime, but are chronic and maybe very debilitating as we have heard. Some have drawn parallels of these symptoms to fibromyalgia and few studies including one by Dr. Steere has documented fibromyalgia occurring after Lyme disease. However, fibromyalgias defined by the American College Of Rheumatology occurs in women far more than men at a ratio of 9:10:1 and no such degree of gender predilection has been found in patients with these symptoms after Lyme disease. Furthermore, in a small study we were able to diagnose fibromyalgia in only 30% of patients with these post Lyme disease symptoms. On the other hand the physical and neurocognitive complaints and the findings on functional testing and even on imaging using brain SPECT scan are similar in fibromyalgia and in these patients.

My suggestion like that of others is that our concept of narrow [Phonetic] [0:07:07] specialty based diagnoses of patients with unexplained somatic symptoms including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, atypical facial pain, TMJ syndrome, noncardiac chest pain syndrome needs revision. These syndromes have more in common than there are apparent differences which suggest and maybe best considered under rubric of a functional or more accurately dysfunctional somatic syndrome. I will now give you some of the features, first thing they are very common, it is estimated that chronic wide spread pain may occur up to 10% of the population 2% of which fulfill the American College Of Rheumatology criteria for fibromyalgia. They are clinically important, they account for up to 20% of consultations in primary care and specialty settings. They are disabling as we have heard. Patients with these conditions can have functional limitations on the order of patients with heart failure. They wax and wean in intensity, but are chronic. They can occur spontaneously, but are often triggered or exacerbated by other processes such as infections.

There is substantial overlapping the definitions of these so called Specific Syndromes in their symptomatology overtime and in the co-occurrence of clinical symptoms. They are often associated with psychiatric comorbidity specially anxiety and depression. Somatization is a common accompanying feature and there is some evidence that it

maybe a primary predisposing feature. These conditions seem refractory to standard medical therapy, although there maybe modest improvement with antidepressants, SSRI medications, and cognitive behavior therapy, but it is clear that a multidisciplinary approach to treatment is best. There is symptom amplification in these patients possibly because of internal factors, such as central sensation in the spinal cord and in the brain. But also because of external psychosocial factors such as disease labeling, naming [Indiscernible] [0:09:33], stress, and even secondary gain. The chronic symptoms after Lyme disease best fit into the category of a functional somatic syndrome. The symptoms are overlapping, nonspecific, chronic, and are not associated with signs of inflammation, active infection, or structural damage. The symptoms are significant and are disabling with important abnormal scores on the fibromyalgia impact questionnaire, SF36 test, etc. These patients often have more psychiatric comorbidity than those who recover completely from Lyme infection. The symptoms are refractory to standard therapy including antibiotics and wax and wean overtime.

Finally there is serious amplification of the clinical symptoms, especially, in our modern society. In part because of disease labeling calling it chronic Lyme disease and a believe in a traditional biomedical explanation of the cause of the symptoms fostered by advocacy groups, media publicity, sympathetic physicians, and prominent individuals in our society. However, it is also our failing a failing of traditional biomedicine both in its lack of understanding of the pathophysiology of these syndromes and its inability to institute effective and durable symptom relief that is partly responsible for our current dilemma with these conditions. Our own focus on biomedical explanations for these patient’s symptoms often leaves us to arrive late at the correct diagnosis and treatment and initiate and perpetuates patient’s beliefs in this disease specific etiology. Therefore, I agree with the recommendations in the 2006 Lyme disease guidelines against excessive and chronic antibiotic treatment for patients with post Lyme disease symptoms.

In the seven pages devoted to this topic there is a reason and the in-depth discussion of the clinical and scientific literature, which demonstrates convincingly that Borrelia infection is not the cause of these chronic symptoms and antibody therapy not the treatment of choice. I disagree, however, with the recommendation of defining post Lyme disease symptoms and syndrome as a unique and specific entity. I myself have been guilty of this in the past, in fact I was one of the first, I believe that clinical and scientific studies of these patients in the context of a functional somatic syndrome will be more likely to shed light on its pathophysiology and appropriate treatment. Thank you.

Dr. Baker: Thank you for your testimony Dr. Weinstein. Let me ask you a question about recategorizing, seeing as you are a rheumatologist and it seems that you have mentioned here that the American College Of Rheumatology does have a definition of fibromyalgia. Are you suggesting that all these syndromes that you list be put in a larger category?

Dr. Weinstein: I’m. I think the Fred Wilson [Phonetic] was lead author on that classification definition also, [Indiscernible] [0:13:18] sorry about what he thinks he has rote [Phonetic] [0:13:22] on us, so that patients who have who don’t fulfill fibromyalgia

criteria then are called not fibromyalgia and they are thought to have perhaps something else. In fact these patients all have similar overlapping complaints and really should be studied as a group, because how else are we going to shed light on pathophysiology and appropriate treatment.

Dr. Baker: Well that leads me into my second question which is pathophysiology. We have heard variety of things, but two things we have heard from you post infectious, from others very similar and an insult on a genetic background leading to something later on. But in my experiences and infectious disease specialist if it’s post infectious or an infectious disease sets off, whatever, typically there is signs of inflammation and so I would like you to comment on that.

Dr. Weinstein: I don’t pretend to know the etiology of these pathphysiology here. I think there are many ways to get to this syndrome. I do believe that if one goes back in time many patients have had a history of somatic complaints dating back to adolescence or early childhood or adolescence late childhood, 20s, so that the fibromyalgia symptoms may start after Lyme disease or aches and pains may start after Lyme disease when they are in their 50s. But if you go back you can find history supportive of a somatic syndrome much earlier than that. So, I don’t know why some people get symptoms in their bowel and others will get joint and muscle complaints and what those different triggers are. But I think they are worthy of study. And I do believe that illnesses that cause aches and pains in these patients are more likely to result in chronic aches and pains or and so that maybe a trigger at one time in their lives. But I don’t think that’s the only symptom complex that they have.

Dr. Baker: Thank you. Other questions from the panel.

Dr. Lantos: Are you aware of continuing research efforts [Indiscernible] [0:15:42].

Dr. Weinstein: I’m, in my department.

Dr. Lantos: And are you aware of… has there been any effort to try and do a multi-growth trial in which antibiotics [Indiscernible] [0:15:59] alone.

Dr. Weinstein: I don’t know, this is more pathophysiology.

Dr. Baker: So one more question from me?

Dr. Weinstein: By the way it’s not me doing the research, it’s somebody…

Dr. Baker: As an infectious disease doctor I try to avoid steroids as a rheumatologist, you sometimes have to use steroids and other anti-inflammatory agents. I haven’t heard much data on using these in the persistent arthritis or some of the other things do you know of data…

Dr. Weinstein: Well in general steroids are ineffective when treating patients with fibromyalgia, so that that is fairly well known. I don’t know specifically about patients with these types of symptoms after Lyme disease, but I would suspect they be relatively ineffective. There is just no evidence that there is an anti-inflammatory basis for this [Indiscernible] [0:16:50].

Dr. Baker: Well then that wouldn’t certainly explain why steroids haven’t been looked at very intensively. Are there other questions? If not, Dr. Weinstein thank you very much.