Thursday, December 13, 2012

5 Part Two: How A Skeptic Ended Up Seeing An ILADS Doctor

In the first installment of this series, the circumstances which gave rise to my seeing an LLMD were outlined. Having issues getting proper diagnosis and treatment for an early acute case of Lyme disease, the inability to secure a referral to an infectious disease specialist, a referral to a doctor from local Lyme disease support groups, and being incredibly ill all led to my first visit with an LLMD.

In today's installment, I'll talk about how I decided to take antibiotics long term, how the Lyme disease patient community became part of my life, and the inner conflicts which have arisen by being a patient with my condition.

On Being A Somewhat Different Chronic Lyme Disease Patient

Unlike the majority of chronic Lyme disease patients who were surveyed, I did not have to see many doctors before my diagnosis. And unlike the majority of chronic Lyme disease patients, I still felt like modern medicine worked pretty well for me up to that point: If I got bronchitis - the doctor helped. If I got a sinus infection - the doctor helped. If I got an ingrown toenail... You get the idea.

So for me, the health care system - at least up until my Lyme disease experience - worked well enough for me. I received as much care as I needed for the problems I faced and made few demands on the system because I was (for the most part) healthy.

This perspective initially carried over to my LLMD: I thought we would have an appointment or two, I'd check in if I had a question or needed a prescription filled; I'd take antibiotics for a few weeks - and otherwise, our paths probably wouldn't cross again unless I got another EM rash someday.

But as I reached the month mark and realized how lousy I felt, I wasn't so sure about stopping antibiotics. I was severely ill. And when I stopped antibiotics, I discovered that within a few days I was even less functional and in even more pain than I was while taking antibiotics.

I told my LLMD, "I don't understand. I thought I'm supposed to feel better by now. I caught this early." My LLMD said, "This is Lyme. This is how it is."

What do you mean, "This is how it is?"

At that point in the game, my brain was so cognitively impaired I had to take notes and try to reason through this explanation given over time - but to be frank, nothing made sense at that point because I was too ill and wasn't tracking conversations well.

I found out that the choice to continue taking antibiotics rapidly became a pragmatic one:

Every time I stopped taking antibiotics, the worst of my symptoms would return and I would drop out of being an active member of society.

With the antibiotics, I was eventually able to walk up and downstairs at a slow to normal speed. I could drive short distances, I could run some errands, I could walk to the train station, and even begin working part time again. I'd still be in some pain and have some fatigue - but I could at least do something.

Without the antibiotics, I would be overcome with pain and fatigue and begin losing cognitive ground again. I would have trouble leaving the bed - let alone leaving the house. The pain and fatigue were so overwhelming that any stoic attempts on my part to push past them failed.

I didn't like this new reality - but I didn't want to lose my job.

I reasoned to myself that I knew a few diseases were treated with longer courses of antibiotics so there was risk management for such situations - and considered treatment was probably low risk, provided I didn't stop antibiotics and restart them often as that would create antibiotic resistance. Or if I decided to stop and wanted to restart - I could restart with a different antibiotic which was effective in order to avoid resistance.

I rationalized my decision at each step, and I did so directly in response to the improvements I experienced while on antibiotics - but also due to the projected loss if I stopped antibiotics entirely.

I knew the risks to continue the drugs were there - and the risks to stop them were as well. I thought I was damned if I did...and damned if I didn't.

The Ups And Downs Of My New Condition

When I first went off antibiotics and symptoms resurgence occurred, I joined a few online support mailing lists for Lyme disease patients and asked if people knew what was happening to me. I was also in so much pain, I wanted someone else to complain to who would understand and not have to dump on my friends about it.

Outside of Lymeland, my healthy friends knew I contracted Lyme disease - but they could not relate to what I was going through. A few of them had Lyme disease in the past and got it treated - but none of them had developed the kind of problems I had. None of them had symptoms which were as severe as mine or had lasted as long.

It was frustrating, because I didn't understand why my path wasn't the same as theirs. It made me wonder just what was in that tick that bit me that I ended up so much sicker than any of them had been.

Not knowing what else to do, I read the posts and archives on my patient mailing lists and struggled to understand what had happened to me. It was challenging because reading and comprehension came very slowly; I had to take notes because I kept forgetting things.

Before I could understand what was happening to me, a clear picture began to form of what life was like for many patients diagnosed with chronic Lyme disease:

- Most people there had symptoms for a long time before they were given a diagnosis of chronic Lyme;
- Most had already seen multiple doctors who had not been able to diagnosis them - or they were diagnosed with something else but were told their case was "atypical";
- Most felt disowned and dismissed by the medical community at large;
- Most if not all had their lives destroyed in some way by the onset of these symptoms which continued plague them.

Patients who were once married were divorced, due to having partners who were unwilling to be supportive or adapt to the reality of their illness. Patients who lost five and six-figure jobs had to sell their homes and downsize considerably - sometimes moving back in with their elderly parents. Patients who were once avid hunters and rock climbers had to stop doing what they loved and either sold their gear or enshrined it prominently in hopes of using it someday in the far off future.

I didn't know what to make of myself and how I fit into all of this as time went on. It was overwhelming to hear how much physical suffering everyone had endured, how much personal loss everyone experienced, and how much humiliation everyone went through at the hands of various medical professionals.

I swore to myself. This wasn't going to be me. After all, I just had early Lyme disease. Not this chronic stuff. Right?

But as time went on, I realized that as early as my infection had been treated, something wasn't right because like the rest of the group - I was still quite sick.

I was barely able to work part time even with extended treatment. I would get home, take off my shoes, and immediately lie down. I would wait two or three hours before getting up to attempt making myself dinner. And after a simple dinner, I would lie down and pass out for the night.

There was no energy to go out and socialize. It hurt too much to return to clubbing, hiking, and biking. My plan to take surfing classes on Hawaii's beaches was scuttled...There was no money to do it, anyway.

Periodically, I would stop all antibiotics and take painkillers and anti-inflammatory medication instead. But each time, the symptoms which made me totally dysfunctional would come back, and I would give in to taking the antibiotics again and double my consumption of yogurt and acidophilus capsules. Pain medication - over the counter and prescription, both - had little effect on the symptoms I had.

Slowly, very slowly, I improved. Months later, I eventually managed to get a new, full time job - and by the time I did, I was about 80% of my pre-tickbite baseline for health. I was initially relieved and thrilled, because to me this meant I'd finally made it. I thought I'd gotten past the Lyme disease, and wrote off remaining 20% of symptoms as residual fatigue and odd random aches which would heal in time.

This little victory was to be short-lived, however, as after many months of no antibiotics (I had decided to quit, having felt mostly better), I began to relive that sinking sense of decline I'd had the previous year. Cognitive abilities began to wane. Energy lacked. More new symptoms I never had before joined the chorus. I fell behind at work. I attempted to telecommute. But long story short: I had to leave this job, too.

I went to my new family doctor and saw a few specialists and tried to figure out if anything else was going on. We tested for autoimmune disorders - nothing. CBC and metabolic panels - nothing. Vitamin deficiencies? Okay, I was slightly low on B-12, but that was easily correctible.

Nothing else showed up, though. And yet I continued to decline and become increasingly useless. Despondent. Exhausted.

Concerned for my sanity, I decided on my own to consult with a therapist and see if depression or other psychiatric conditions could be causing any of my symptoms. The therapist's evaluation of my situation was that I was somewhat depressed, but the nature and magnitude of my symptoms indicated I had a medical problem that wasn't being properly addressed. What problem? The therapist had no idea.

Not finding any answers from my family doctor, specialists, or therapist, I returned to my LLMD. There, the reason for some of the absolute worst of my symptoms had been revealed: My spiking fevers, sweats, chest compression, and shortness of breath which began attacking at night were pinned down to babesiosis, a tickborne disease caused by babesia - protozoa which cause symptoms similar to malaria. The grinding fatigue and cognitive slowing I'd been struggling with may also have been caused by this organism.

It turned out babesia treatment was the best investment I ever made since the entire Lyme disease debacle began, as it began to alleviate my most serious symptoms. It enabled me to sleep more than three hours a night, restored a huge chunk of my cognitive ability, stopped sharp stabbing pains in my legs, and restored my breathing to normal.

I improved, but to this day have still not returned to my former health before the tick bite.

Trying To Make Sense Of It All

A couple years prior to this point, I went into my situation expecting to take a couple weeks' worth of antibiotics then go back to work. I didn't expect to experience not only a protracted improvement - but also an improvement followed by a more serious decline.

After my cognitive abilities began to improve again, I tried to make sense of my situation: On one hand, clinical trials had shown that only a subset of the most symptomatic patients enrolled improved with additional antibiotic treatment. But on the other hand, I had my own experience with antibiotics over a longer trajectory than those in trials, and had seen greater improvement. On one hand, anecdote is not evidence. On the other hand, I had nothing else to go on because there was no officially sanctioned treatment from the Infectious Disease Society of America, who labeled my condition as being "Post Lyme Disease Syndrome" - hypothesized to be an autoimmune-like disorder.

Tired of having either the contested and hotly debated chronic Lyme disease or the ill-defined Post Lyme Disease Syndrome, I wanted answers. Where were they? Where was the scientific research which would determine my diagnosis without any doubt?

My patient support groups and research I'd read reinforced the idea that Borrelia burgdorferi could cause a persistent infection. But I'd also read that molecular mimicry was associated with Lyme arthritis - at least in some instances. I began to read through all the research I could find, and see if I could independently draw my own conclusions about my condition.

I half jokingly wanted someone to conduct a clinical trial pitting antibiotics against non-antibiotic analogs which contained the anti-inflammatory component. I thought maybe this would answer some questions as to whether it was the anti-inflammatory component of antibiotics which alleviated patients' symptoms - or the antibacterial one. But it was quickly pointed out to me that if any patients were still infected, this would be considered an unethical trial if those patients were placed in the analog arm. I dropped that idea.

I had looked to enroll in clinical treatment trials for either chronic Lyme disease or Post Lyme Disease Syndrome, willing to bet on either horse in this race - but neither was ever running on the NIH-NIAID track whenever I looked. And to this day, there has been no Post Lyme Disease Syndrome treatment trial, and no test of the hypothesis that PLDS - outside of Lyme arthritis - is autoimmune in nature. So my career as a lab rat was over before it could even start.

I wanted to do everything right, and not rely on anecdote alone for my treatment - even if it showed some signs of success. I looked for how I could engage in the research needed to help myself and others - but there was no avenue open for this, either.

So here I was, stuck doing something which I didn't think I'd be doing in the first place and which I wanted to understand: How could I have ended up taking antibiotics longer term when officially published trials indicated that more antibiotics were not better? I thought that as someone with a research background, that I would have used the outcome of those trials as a basis for my decision. I didn't.

One could argue I did it out of desperation. That's probably true. I was so seriously sick, I didn't know what else to do. I was desperate for relief and at one point, nearly suicidal with pain. So desperation played a role - there is no denying that. It was the reality of the situation.

But it really began with the need for a short course of antibiotics to begin with - and ending up continuing it because the alternative was much worse.

And at the time, it was really the only option presented to me by any medical professional outside of pain medicine, and I needed to make sure my brain worked in order to hold down even a part time job - opiates and narcotic pain medicine would have stolen away what brains I had.

I did it because no other options were presented to me, no one else knew how to treat my condition, and the boundaries defining my condition were ill-defined. I definitely had Lyme disease - at least at one point. I definitely had babesia, and now I can never donate blood again. I don't know if any other pathogen was in that tick and will likely never know; perhaps some entirely different microorganism which was antibiotic responsive was killed off by my efforts.

After some time has passed, I've noted that the most severe of my symptoms have not returned. I'm hesitant to say they're permanently gone, given how I was at 80% of my baseline before, only to decline again. And while I'm not well enough to work, I'm not so disabled I can't get out of bed and do a number of basic tasks - provided I pace myself.

Arriving at this stage, I have had to reevaluate how I decide to treat my condition. Since I'm concerned about antibiotic resistance and allergies, I wanted to avoid taking more antibiotics. And since I'm concerned about the condition of my digestive system, I thought stopping antibiotics was in my best interest. So I have stopped again, and tried other methods of treating my symptoms - but none have been effective enough to worth noting.

Today, life goes on - to some degree. I am not improving. I miss working. I miss doing all the things I love to do that I - like so many others on the mailing lists I inhabited - cannot do.

And I debate about what to do next - especially if my symptoms deteriorate more. I am on a rollercoaster where I can't be sure how I'm going to be affected next, and most of the medical community seems ill equipped to know how to manage a patient with my condition.

This is not a blame thing, by the way - this is a simple fact. And yet, if the projections are anything to go by, I am the medical face representing tomorrow's patients: More of us are going to be chronically ill, and have to cope with complex conditions. What can we do to set the groundwork in place to prevent others from becoming chronically ill as I have - and to effectively help those who have become as ill as I am?

(Part three of this series next: The pseudoscience and science of chronic Lyme disease. Part one of this series is here.)

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Wednesday, December 5, 2012

7 Part One: How A Skeptic Ended Up Seeing An ILADS Doctor

Early November 2012, the International Lyme and Associated Diseases Society - also known as ILADS - held their annual conference in Boston, Massachussetts. Due to the incoming frankenstorm, Sandy -  and other reasons - I did not attend the conference. Instead, I joined hundreds of viewers in watching a prerecorded version of different ILADS conference presentations on livestream last weekend.

I was originally going to give my own bullet summary about each of the conference presentations I viewed - but I think that if you are interested in what each of the presenters had to say, it's best to view a replay of their presentations during the next two weekends and view their slides on the ILADS website. It is going to take me a long time to write on the presentations I intend to single out.

(I did write a quick overview of my initial impressions of the streamed video feed on a thread on Lymenet Europe, and that - along with other conference watchers' opinions - can be found here: Thoughts re ILADS 2012 Streamed Conference, Dec. 1-2 )

But before I write more extensively on specific conference presentations (and also grade them based on how much they are evidence-based) what I want to do today is share part one of a series of posts on how it is I got involved with ILADS and LLMDs in the first place. Not only as a patient - but as a skeptic.

This series will hopefully shed some light on how someone like me would fall into ILADS' orbit instead of accepting the Infectious Disease Society of America's guidelines for the treatment of Lyme disease, and explain how someone like me has come to view the issue of chronic Lyme disease after several years of living with persisting symptoms.

How I Ended Up Seeing An LLMD

It's important to offer some backstory so you know how I came to know ILADS doctors, and how some patients with similar backgrounds such as my own may end up seeing an ILADS doctor - or even more generally, what is called a Lyme Literate Medical Doctor (LLMD).

It should be noted that the term "Lyme literate doctor" is in and of itself almost meaningless to most people, and in various circles it can mean anything from an infectious disease specialist to a doctor who knows enough about Lyme disease to know it when he sees it and will treat it. For the sake of discussion here, a Lyme literate doctor is one who knows about multiple tickborne infections, is willing to treat patients using longer courses of antibiotics than the IDSA guidelines state, and does not put a hard limit on either treatment duration or dosage.

But I digress... Here's my story:

One day several years ago I went for the hike in the mountains, and that evening, found a tick embedded in my back. I was alone, there was no one else around to remove it, and I am certain I removed it improperly.

Fast forward... I developed a rash around the bite site, and went to a local clinic to get it checked out. I was told I was having a localized allergic reaction to the bite, and that there wasn't any Lyme disease in the area I'd been bitten. In fact, I was told Lyme didn't exist in the area and was rare in the state.

The doctor gave me a prophylactic dose of doxycycline, but little did I know at the time that it wouldn't be enough. In another week, my rash had expanded, I felt like I was getting a flu, and I returned to the clinic - only to be prescribed Zithromax and get diagnosed with a sinus infection. I got very sick after I finished my Z-pack (the full story in all its gory detail is on this page), had to get dropped off at the door to the clinic rather than walk there, and during my appointment was told again that I couldn't have Lyme disease. Lyme disease wasn't endemic to the area in which I'd been bitten. But nonetheless, a blood draw for an ELISA was taken at my insistence.

The test result came back negative, and I was told that I did not have Lyme disease. However, what I did not know at the time - and learned later - is that people don't always immediately produce antibodies to Borrelia burgdorferi, the bacteria which causes Lyme disease. It can take 4-6 weeks to produce a positive antibody response.

I also learned later that taking antibiotics early in infection can abrogate the immune response to the degree that antibodies may not register on the test even if you are infected. (Fortunately, this was not the case with me, as some time later I did have a positive test.)

Even the Centers For Disease Control (CDC) - viewed by many chronic Lyme disease patients as being too restrictive in its approach to diagnostic criteria, testing, and treatment of Lyme disease - has made it clear that these two factors can lead to a false negative in testing for early Lyme disease.

By now, you might be sitting there wondering where I'm going with all this. It's this simple:

My family doctor knew nothing about Lyme disease.

My (now ex) family doctor did not think I had Lyme disease because of where I was bitten - and missed the pathognomonic (which means a symptom which is the gold standard for diagnosis) sign of Lyme disease which should have led to my immediate treatment with a few weeks of doxycycline - if not a few weeks of IV Ceftriaxone.

The doctor did not even treat me based on the IDSA's own guidelines when they should have.

I am considered in the minority among chronic Lyme disease patients - at least so far as I know. The largest survey of chronic Lyme disease patients that I know of was conducted by Lorraine Johnson of, a patient advocacy organization. The results indicated that in their survey of over 4,500 patients with chronic Lyme, 73% were not diagnosed within a year. And many patients report not remembering receiving a tick bite, not seeing an EM rash, and having to see numerous doctors before receiving a diagnosis of Lyme disease.

This was not me. I am the person who, in many ways, was already an outlier in life - and now I had become an outlier among outliers; the estranged among the estranged.

Had my family doctor known what I had and referred me to an infectious disease specialist immediately - and had that specialist seen the severity of my symptoms - odds are good I would not be here writing all this here for you to read.

But between having gone online to contact Lyme disease support groups for a referral, and my inability to get a referral to an infectious disease specialist, I ended up seeing a LLMD for diagnosis and treatment.

My LLMD told me that I was in fact a textbook case of Lyme disease, and it was astonishing that I had not received treatment right away. I agreed, knowing exactly what happened to me and just how seriously ill I was, I did not understand why this happened to me.

When I returned to the original clinic a couple times, enlarging EM rash and all, that should have been the signal to act. Instead, it was written off.

My LLMD informed me that he and the state health department knew the region in which I'd been hiking was endemic for Lyme disease, and further follow up with the state health department confirmed this as true. My LLMD immediately gave me my first round of antibiotic treatment, and while I should have had IV antibiotics, I could not because insurance would not cover it. I also could not afford to pay for it out of pocket because I stopped working when I got too sick.

I had a test for Lyme disease and at that point, my test was positive. And as I continued to get sicker while on treatment, my LLMD suspected I had a coinfection and tested me for a few - of which babesiosis also came back positive, and it made sense because my symptom presentation matched the diagnosis.

What I experienced early on in this LLMD's office was not what I'd experienced in my local clinic. First, the LLMD knew about early Lyme disease and knew where endemic areas in the state were. I had no idea where they were - nor did the previous doctor I'd seen. The LLMD was well informed about different coinfections ticks can carry. At the time, I knew nothing about coinfections - and I barely knew anything about Lyme. The LLMD also ran additional tests to rule out other conditions at the time, and make sure nothing outside of tickborne infection was missed. I appreciated the thorough analysis.

The appointment was thorough, and I got the impression my new LLMD was more competent than the doctors I had seen in my local clinic. And over the following months, this LLMD's treatment took me from being unable to think straight, hardly being able to walk, and being in so much pain I had been contemplating suicide to slowly thinking again and walking from the bedroom to the mailbox and back.

So here are the factors which lead to my getting involved with the world of LLMDs and ILADS:

- Repeated misdiagnosis of early infection by my family doctor when I had a glaringly obvious EM rash.
- Being denied a diagnosis due to a negative ELISA when the doctor should have known it was given too early to result in a positive test.
- The inability to get a referral to an infectious disease specialist.
- The impression that the LLMD was knowledgable and competent, and more knowledgable and competent than doctors at my clinic.
- Being believed that I was in fact as severely ill as I had stated.
- Receiving an extensive exam and having a full medical history taken - more time was spent with me than any doctor had ever spent on me.
- Being given tests to rule out any other conditions - both tickborne coinfections and non-tickborne related medical conditions.

So to any family doctors who are out there who have a patient in front of them with an expanding dark red oval rash with no central clearing and a tick bite in the middle of it: Treat them. Don't wait for a positive blood test result. A little doxycycline goes a long way in early Lyme disease and helps patients avoid becoming a late stage case or take on this controversial diagnosis of chronic Lyme disease.

But the number one factor which landed me in the LLMD's office cannot be emphasized enough:

I was very, VERY sick. Sicker than I had ever been in my entire life. What I had did not feel like a mild or even moderate flu-like illness. I had so much pain in my body, it felt bone-breaking. I had a high fever and shortness of breath. I had so much inflammation and weakness in my arms that I could not wash my own back. I could not stand in the shower. This went on for weeks, and did not match in magnitude or form the experience that a patient, John, describes of his own brush with Lyme disease on the CDC's website.

I needed to see someone who would treat me, and I wasn't going to go to some alternative doctor who was going to give me herbs and supplements and send me on my way. The clinic had already blown me off. And my friends were concerned about me - some even thought with my symptoms that I should see a neurologist - but getting an appointment for one had its own slow timeline.

When I ended up looking online and called a few local Lyme disease support groups and told them about what happened to me and asked which clinic I should go to, I was informed by multiple members of these groups that my experience was not that uncommon; that I was better off getting an appointment with an LLMD right away.

Lyme disease patient advocacy played a role in my getting to see a LLMD. Before I had made any of my phone calls, I had never heard of an LLMD nor did I know what it meant. I did not know all about how LLMDs treated patients. All I knew was that I had contracted Lyme disease recently and needed help. And who else do you call about specific diseases outside of doctors who treat them other than other patients who have them?

At that stage, I did not know there was a controversy surrounding Lyme disease. That would come later. All I knew at this stage was that I had early Lyme disease and it needed treating. The pain needed to stop - and stop soon.

(Part Two next: How I decided to take antibiotics long term, how the Lyme disease patient community became part of my life, and the inner conflicts which have arisen by being a patient with my condition. Followed up by Part Three: Lyme disease pseudoscience and science.)

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Friday, November 30, 2012

0 Placeholder: ILADS 2012 Conference Remarks

Coming soon... ILADS 2012 Conference Remarks - watch this space.

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0 Late November Newsletter From Camp Other

There are a few announcements I'd like to make today...

For those of you who are here for the first time, via Twitter: Welcome to Camp Other blog. I'm glad to see you here, and I look forward to having interesting discussions with you both here and on Twitter.

Whether you are new to this blog or a returning visitor, the following announcements may help you make sense of what's been happening here at Camp Other blog:

An Effort to Change Writing Style and Reporting

Joining Twitter is a recent move I made in the past couple of weeks in order to pick up more great writing on science and links to posts from science bloggers.

In some ways, this is great because I'm learning more, and I recommend following those I follow because there are a lot of interesting articles out there. But in other ways, this is a humbling experience because there are so many good writers out there - and once I've read them, I can't help but notice there is room for improvement here.

I'm not a professional blogger and do what I do for my own education and share it with others. I never attempted to make this blog a profitable enterprise because I felt that the information was something everyone should have and I wanted to remain neutral by not being funded by anyone who could be perceived as having editorial influence over my posts. This is how it has been - and this is how I want this site to continue - even if someday I manage to become a professional writer in the future.

Open source or not, after reading more science blogs and articles, I can only see that learning from those already in the trenches longer than I have been will teach me how to be a better blogger for everyone.

One thing I am already noticing, unfortunately, is that blogs which are more accessible than mine in some way - those which reach a wider audience, or those which are high volume and have short,  focused posts - are blogs which are going to be difficult for me to emulate.

Reason being: I am suffering from a medical condition which affects my cognitive abilities and energy. My ability to either stay focused on one topic or publish a brief post is challenged due to having chronic fatigue and trouble focusing.

Ironically, having more fatigue doesn't translate into shorter posts - it comes coupled with altered executive function in my brain - so I can ramble on and write a long post yet have trouble getting to the point.

I'd like to make an effort to change this, but where to begin? I could use some advice as to how to overcome these stumbling blocks and make my blog not only more easily readable for a wider audience but also optimize and work with the cognitive abilities I do have.

REMOVED: The Poll On What Causes Persisting Symptoms of Lyme Disease

For almost a year, a blogspot poll widget was on the upper lefthand corner of this blog. It asked readers to select among a number of choices as to the cause for persisting symptoms in patients after initial treatment of Lyme disease.

In recent weeks I have been monitoring the output of this widget and decided in all fairness it needed to be removed because votes were not being recorded and displayed accurately: One week I would see a score of over 110 votes, and the following week it would dip down to 93 - only to waver between 97 and 92 in the following weeks.

Any poll should be gaining and not losing the total number of votes. So it got voted off the Camp Other island, and I won't be using that widget again. Other online sources reported similar issues with this widget as well, and had I known in advance it was a problem, I would have used a different poll widget.

Despite this setback, know that each choice and the most recent results will be discussed in a future post.

A sneak preview: A little over 90% of readers who responded to the poll thought that Lyme disease can be a chronic and persisting infection after initial treatment - while a little over 30% thought persisting symptoms that occur after initial treatment are caused by an autoimmune condition.

The Challenge Of Being Both A Patient And Researcher: Bias

I placed a request on Twitter earlier today asking followers for any information on scientists who study the disease they themselves have - and in particular, blog about it.

I'm hoping to ask them a few questions about how they handle the issue of bias, and how they sort out other research they read about their own condition in order to know which leads to follow, which leads are cold, and which leads are questionable.

One of the walls I find myself banging against as I continue to write this blog is my concern over the issue of bias: Can a patient research their own disease and its causes and treatment without bias, or is there always going to be a certain amount of bias in what one reads and writes about because one is a patient?

Not sure I can sort out all the issues around this, but I wanted to bring up the question because I think it is an important one. I'd like to explore this more.

Sick, Symptomatic, And Struggling

I mention it only in passing because I am still not posting as frequently as I hoped:

I'm not doing so well lately. I suspect the symptoms I'm having are due to a new condition and I am in the middle of getting referrals to specialists to help sort it all out. In the meantime, hopefully I can find a way to continue to do research and blog more regularly.

And there is a certain level of frustration I'm experiencing here which is difficult to put into words, but it basically boils down to, "I'm sick and tired of being sick and tired, and sick of being poked, prodded, biopsied, scanned, bled, x-rayed, ultra-sounded, and analyzed in general."

I am not a number... but I have felt like one. (I'd rather say, "I am not a number, I'm a free man" - but I'm not sure how many of you reading along would catch that ref.)

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2 A Pocket Review of Dr. Steere's NEJM Reinfection Editorial

I finally had the opportunity to sit down and read Dr. Steere's editorial which accompanied Nadelman et al's study, "Differentiation of Reinfection from Relapse in Recurrent Lyme Disease".

Before I comment on the editorial, I want to acknowledge the research which was accomplished in the study as it deserves more attention.

I think it was an interesting study on two counts:

One, it showed that in a group of 17 patients, it was highly unlikely that a patient would get reinfected with the same genotype of Borrelia burgdorferi compared to one with which they'd previously been infected. Does this suggest that patients have some form of immunity to specific genotypes - or is this a reflection of random chance of infection with specific genotypes?

Two, it provided evidence in two patients that a person can be infected with one genotype of Borrelia burgdorferi in skin - while an entirely different genotype can be found in the blood. The significance of this has yet to be determined, but it does raise some interesting questions about the nature of Borrelia burgdorferi infection. How often are patients coinfected with different types of Borrelia burgdorferi? Are these genotypes competitive in any way? Can one genotype affect a patient more profoundly than the other? If there is a delay in treatment, can one genotype be more effectively treated than another?

The findings from this study inspire curiosity and more questions about the nature of Lyme disease.

Thoughts on the editorial, "Reinfection versus Relaspe in Lyme Disease"

Now that I have acknowledged two interesting findings from the Nadelman reinfection study, I have to say that unlike the connections made by Dr. Steere, I do not see the relationship between data presented in this study and patients who have been infected with Lyme disease and continue to have persisting symptoms after initial treatment.

Any good study and its findings stand on their own and an editorial on them by the authors themselves is usually unnecessary. The work should speak for itself, and I think this study does well to demonstrate a relationship between the presence of new genotypes and reinfection in a small group of patients who were bitten by ticks in the same geographic location.

If there is an editorial accompanying research, it should in some way enhance or broaden our understanding and appreciation of the findings - and by extension, lead our curiosity to new horizons.

Unfortunately, Dr. Steere's editorial is not additive in nature. It does not add nuance to or a greater appreciation of the reinfection study - nor does it address the kind of questions raised above which directly apply to his study. Instead, his editorial seems to stretch the findings' significance in order to provoke discussion on chronic Lyme disease based on claims that a small percentage of patients' erythema migrans rashes have been thought to indicate a relapsing infection.

Robert B. Nadelman, M.D., Klára Hanincová, Ph.D., Priyanka Mukherjee, B.S., Dionysios Liveris, Ph.D., John Nowakowski, M.D., Donna McKenna, A.N.P., Dustin Brisson, Ph.D., Denise Cooper, B.S., Susan Bittker, M.S., Gul Madison, M.D., Diane Holmgren, R.N., Ira Schwartz, Ph.D., and Gary P. Wormser, M.D. Differentiation of Reinfection from Relapse in Recurrent Lyme Disease. N Engl J Med 2012; 367:1883-1890November 15, 2012DOI: 10.1056/NEJMoa1114362
Allen C. Steere, M.D. Reinfection versus Relapse in Lyme Disease. N Engl J Med 2012; 367:1950-1951November 15, 2012DOI: 10.1056/NEJMe1211361

ALSO, to read my detailed report on the Nadelman reinfection study, see:

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Friday, November 23, 2012

0 Lyme Research Alliance Response To Reporting On Reinfection Study

The executive director of the Lyme Research Alliance responded to the New York Times' article, “New Infection, Not Relapse, Brings Back Lyme Symptoms, Study Says” which refers to the Lyme disease reinfection study recently published in the NEJM:

(original text removed in observance of NYT copyright policy.)

Current Active Research Projects which are listed on LRA's site:

For the most part, I agree with Mr. Wild's statement. I only have some questions about this sentence: "This limited study supports the theory that Lyme is effectively treated by one short course of antibiotics, yet numerous scientists vehemently disagree."

I would have phrased it differently and stated it as "This limited study supports the theory that Lyme disease is always effectively treated by one short course of antibiotics, yet numerous scientists vehemently disagree."

There is a body of research which provides evidence that Lyme disease is not always effectively treated with one short course of antibiotics - even the IDSA's 2006 Guidelines state up to 10% of early acute cases of Lyme disease result in treatment failures. Those same guidelines cite studies on late stage Lyme disease cases which are treated according to the guidelines, yet patients are recorded as having relapses and not returning to their former health pre-infection.

In addition to the guidelines, there are case studies, research studies, and individual patient reports of relapsing symptoms after initial treatment.

At the same time, not everyone who contracts Lyme disease goes on to have persisting symptoms after initial treatment. The reason why some patients develop chronic Lyme disease and some do not is not clear. A delay in receiving initial antibiotic treatment appears to play a role - and the genotype of bacteria infecting a given patient and the patient's immune profile may also play a role in development of persisting symptoms. More research is required to understand the cause of chronic Lyme disease.

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Wednesday, November 21, 2012

1 What Does The Reinfection Study Have To Do With Chronic Lyme or Post Lyme Disease?

Last week, a number of media outlets wrote articles referring to a study published in the New England Journal of Medicine (NEJM), "Differentiation of Reinfection from Relapse in Recurrent Lyme Disease".

Since I wanted to see what was actually stated in the study, I acquired a copy of the full text of this publication to see for myself why the authors might have given some journalists the impression that chronic Lyme disease - or even post Lyme disease syndrome - does not exist.

Side note: One important thing to know is that at the time I wrote this entry, I had not read the accompanying editorial by Dr. Steere which was published in NEJM. Given that the current entry was written based only on the study itself and has gotten quite lengthy, I will be writing separately about the editorial in the future.

Summing it up

After reading through the paper, if I had to give a one sentence summary of what this study accomplished, this sentence at the end of it summed it up fairly well:
"These data, in conjunction with available clinical and epidemiologic evidence, show that repeat episodes of erythema migrans in appropriately treated patients were reinfections and not relapses."

If I'm to take it at face value, what this study does is provide evidence that when patients were properly treated early for previous erythema migrans (EM) rashes in the past and they presented with new EM rashes with obvious tick bites - they almost always contained a different kind of Lyme disease than one with which the patients had previously been infected. And with early treatment of patients found with new EM, most of those patients will go on to be fine until they are reinfected again.

Seems to make sense to me.

This is what the study appears to have discovered, so at first glance I had yet to see what the findings in this paper have to do with evidence that chronic Lyme disease does not exist. Nor did I see where this study provides evidence that post Lyme disease syndrome does not exist, either.

However, after digging a little deeper, I found one statement which suggested that data found in this study implied that chronic Lyme disease does not occur:
"[...] some persons have attributed recurrent episodes of erythema migrans to relapses in patients treated with recommended courses of antibiotic therapy; they cited experiments in animals that showed persistence of B. burgdorferi despite antibiotic treatment."
This was about as close as I could get to finding a statement in the study that chronic Lyme disease does not occur, as the majority of the content of the paper focuses on the fact that new erythema migrans are associated with new infections.

But one thing which I have stated before was that when it comes to Lyme disease, the rash is not the disease. The rash is a symptom of early infection. Untreated, it will eventually disappear. It may never recur during the same episode of infection. And in the meantime, depending on the strain one has, host factors, and without proper treatment, the infection will disseminate and spread to areas of the body far removed from where the rash first appeared.

Because the patients in this study were treated either during the first sign of cutaneous infection or very early disseminated infection, they were far more likely to have been successfully treated than patients for which there was a delay in treatment or patients who were improperly treated (say with a shorter duration, or possibly a less effective or an incorrect antibiotic) earlier.

Anyway, I have a few remarks on the paper:

On the significance of EM rashes under other conditions

One of the concerns I mentioned elsewhere after reading online article after article was that journalists had not mentioned how EM rashes were relevant not only as a symptom of early infection but at other points.

To some degree - and to my satisfaction - one paragraph of the study covered other reasons EM rashes would appear outside of the first sign of infection, and mentioned that an EM rash can show up and disappear only to reappear in untreated patients and also inappropriately treated patients.

This is important to note, and I would hope that family and urgent care doctors can use the presence and timing of an EM rash relative to other symptoms to determine when more treatment is required. Dr. Jorge Benach has stated that satellite EM rashes which erupt within weeks to months after the initial EM are a sign of disseminated infection.[1] Dr. Brian Fallon of the Columbia University Lyme and Tickborne Disease Research Center has also made the same observation.[2] Combined with other clinical evidence and symptom presentation, patients with these rashes may require additional oral or intravenous antibiotic treatment.

Patients with new EM rashes have been reinfected.

In addition to the summary statment cited earlier, one should take note of this particular passage in the study:
"Patients were treated with standard courses of antibiotics at each episode of erythema migrans, with subsequent resolution of the skin lesion or lesions."
The key words to keep in mind here are: "erythema migrans" and "appropriately treated patients".

This study is about early acute Lyme disease including early disseminated infection. The patients who were followed during the course of the study were all treated for signs of early acute Lyme disease - not late stage, persisting disease.

Based on this, I suspect the authors want readers to take away from their study is that these 17 patients who have an EM rash and are treated early in their infection have successful resolution of their Lyme disease - and any new EM rashes they have are a sign of a new infection which requires more antibiotics.

In other words: Early treatment is the key to greater success in treating Lyme disease effectively.

The value of finding different OspC RST types in different EMs.

The keystone of the study is the evidence that different OspC RST types are found in each episode of EM when patients are followed over time.

What does OspC RST strain mean? Citing a definition from an earlier paper:
"Two genetically linked typing systems, one based on sequence variation of outer surface protein C (OspC) and the other on ribosomal RNA intergenic spacer type (RST), have been used to classify US B. burgdorferi strains.

OspC typing divides B. burgdorferi strains into 21 genetically distinct types, 16 of which have been identified in the northeastern United States and RST divides B. burgdorferi into three groups.

RST1 corresponds to OspC genotypes A and B; RST2 corresponds to OspC types F, H, K, and N; and RST3 corresponds to the remaining 10 OspC types, including D, E, G, and I.

In the northeastern United States, infection with OspC type A (the most common RST1 strain) or OspC type K (the most common RST2 strain) accounts for approximately 60% of Lyme disease cases; and all of the OspC types within the RST1 and RST2 groups account for approximately 80% of cases. RST3, the least common type, is the most diverse, although infection with OspC type I accounts for approximately half of the RST3 cases.

Because RST typing of isolates may miss differences within groups and because OspC typing may lead to small groups, more information for clinical correlations can be obtained from the use of both typing systems."[3]
The above description of how OspC RST typing is taken from the paper, "Borrelia burgdorferi RST1 (OspC Type A) Genotype Is Associated with Greater Inflammation and More Severe Lyme Disease".

What is known not only from this paper but from many other papers is that different genotypes of Borrelia burgdorferi exist and may affect the clinical presentation of Lyme disease over time.[4-11]

And as time goes on, new genotypes are also found to spread hematogenously. However, it is important to keep in mind that just because a genotype can disseminate easily does not mean it is going to cause as much inflammation or have a particular tissue tropism.

For example:
"[...] However, when mice were infected by tick bite, as in the natural infection, RST 1 isolates displayed higher densities in blood, but the number of spirochetes in the heart or bladder was similar with either RST 1 or RST 3 strains (14). This suggests that in the natural infection, smaller numbers of RST 3 organisms, which may not be detectable in blood, are still able to spread to the joints and cause infection there. Consistent with this observation, the frequencies of B. burgdorferi genotypes in human patients in the current study were similar in EM skin lesions and in joints. Thus, it seems that all 3 RSTs have a similar predilection for dissemination, but larger numbers of RST 1 organisms are more often detectable in blood."[12 ]
According to research to date, the B. burgdorferi RST1 (OspC type A) genotype - followed by the RST3 (OspC type I) genotype - cause greater inflammation and more severe disease than other genotypes, establishing a link between spirochetal virulence and host inflammation.[ 3]

It gets more complicated from here. Researchers are still learning how these different genotypes and subtypes interact with their hosts and host immunity.

According to research (as is stated above) OspC type A RST1 and OspC type K RST2 account for approximately 60% of Lyme disease cases in the northeastern United States.

Judging from other publications, northeastern US OspC genotypes more or less break down into this list:

- Osp type K RST2 accounts for about 40% of that 60%.
- OspC type A RST1 accounts for 20% of that 60%.
- 20% of northeastern United States genotypes are mostly other RST1 and RST2 types.
- The remaining 20% are a mix of RST3 which is dominated by OspC I RST3.

That these different genotypes exist and have different pathogenicity is a fairly recent discovery and it is only just beginning to be understood.

More is understood about more common OspC types than less common RST3 strains which are highly variable and found less frequently in animal and human hosts. Additional research on these genotypes is needed.

So what kind of OspC RST types did patients have in this study on reinfection? It's a good question to ask, because if patients have genotypes of Borrelia burgdorferi which are more likely to lead to dissemination, then they (potentially) have a greater chance of invading more immune-privileged spots, such as joints, tissues, organs, and the central nervous system.

Based on a review of the overall breakdown of different OspC RST types in this study, they did align somewhat with previous research on northeastern United States genotypes.

OspC K RST2 was the dominant genotype found in skin, followed by a mix of OspC RST3 types then OspC RST1. That OspC RST3 types were more common than OspC RST1 differed from earlier research. Blood samples were somewhat different than those found in skin, with a combination of RST1 and RST3 types collectively outnumbering OspC RST2.

There are some data sets which were not collected during this study which I would have wanted to see. For one thing, Borrelia burgdorferi samples were not taken from synovial fluid or cerebrospinal fluid (CSF) for OspC RST typing. We would also be missing any data from tissue biopsies as these are not routinely done, and are rather invasive for the patient. On the immunological side, the genetic backgrounds of patients with specific HLA-DRs were not revealed.

How this study does (or doesn't) relate to Chronic Lyme disease or post Lyme disease syndrome

Patients with early disseminated infection were said to have had fever, arthralgias, headache, or fatigue which were present during the first episode of EM. The authors expanded on this point over time, demonstrating that in these 17 patients, early disseminated infection and more invasive genotypes (such as ospC A RST1 or ospC I RST3) were handily cured with a prompt course of antibiotics and that any future symptoms would be related to a new infection and not a relapse.

Based on the OspC type data, the only way I can see that this study might be trying to disprove the existence of chronic Lyme disease is the authors' position that the evidence demonstrates that the same virulent strains found during the first episode EM rash that were treated were not present during the second episode in any patient. Therefore, by their deduction, the Borrelia bacteria did not persist in the time between EM rash episodes.

In their opinion, evidence of a relapse would have been shown if the patient's samples demonstrated that the same Borrelia burgdorferi genotype would be present during both episodes of EM.

However, is this the only conclusion one can draw from such a study? I have unanswered questions about it.

Can the genetic background and varying immune system responses affect the course of Lyme disease in host mammals? (I already know the answer is yes here, but what I know is mostly about animal models. Is enough known about this as it relates to people?)

How likely it is that an existing genotype of Borrelia burgdorferi found in tissues and CNS will migrate to the blood and EM rashes during ticks feeding on humans?

In the study, given that in two patients the genotype of Borrelia burgdorferi from one skin sample did not match the genotype of that found in blood during the same episode, is there a possibility that in a handful of cases, antibiotics could successfully treat the EM rash produced by one genotype while not successfully treating a more virulent and invasive genotype if the infection had advanced for some time without treatment - say to more remote tissues such as organs or the CNS?

Could a previous infection with a Borrelia burgdorferi genotype with specific tissue tropism coexist with the onset of an EM rash containing a new genotype?

What happens if a patient has previous infection in which no EM rash was present or seen and it goes untreated - then that patient acquires a new infection with an EM rash on top of the first infection?

I don't know the answer to these questions or how likely these scenarios are, but I suspect the last one I mention above is not entirely uncommon.

Either way, based on the patient background which is supplied in this study we cannot know because patients are reported as being treated successfully during the early stages of infection.

I also don't know how often it occurs that a patient has persisting symptoms after initial treatment for Lyme disease and a new erthyema migrans is never seen during the course of their persisting symptoms.

Given my experience as a patient, I can only make the observation that other patients in my situation seldom report seeing new rashes during the course of their condition. I think researchers should take a close look at the subset of those patients who are most severely ill and are housebound - they are an important subgroup to study because their odds of reinfection are very low.

Related to this, there is one immediate key difference I also see between the patient group studied and chronic Lyme disease patients:

The patient population in this group received a course of antibiotics each time an EM rash presented itself. Because they were treated early, presumably they had a good chance at recovering completely from their infection.

Chronic Lyme disease patients and their doctors alike report that many chronic Lyme disease patients' conditions are discovered late, and symptoms and serology often reflect those of late stage Lyme disease patients - not early acute or early disseminated patients.

It is this difference which makes me wonder about the applicability of such a study to a condition such as chronic Lyme disease or post Lyme disease syndrome.

Patients with late stage Lyme disease are less effectively treated with antibiotics and can be refractory to treatment; studies cited in the 2006 IDSA Lyme disease treatment guidelines indicate that a fair percentage of late stage Lyme disease patients do not fully recover after antibiotic treatment - though the reason why is not entirely clear.[13]

Development of an autoimmune-like condition has been hypothesized by the IDSA and various researchers as being the cause for persisting symptoms after initial infection, while other researchers suspect persisting infection might occur in some patients.

In the end...

The study provides evidence that in 17 patients who are properly treated with antibiotics shortly after EM rashes appear, their infections resolve and they get new infections.

If one supports a model of chronic Lyme disease and thinks that Borrelia burgdorferi can persist in the human host past initial treatment, then this study won't provide evidence either way as to whether or not this is the case:

Part of the definition of chronic Lyme disease hinges on patients having been treated late in infection and/or treated improperly early in infection only to go on to develop later stage Lyme disease in the future.

If one applies this definition, it is important to note that none of the patients in this study had a delay in treatment and proceeded to late stage symptoms before receiving antibiotic treatment. None of the patients were reported as showing signs or symptoms of Lyme disease between episodes of EM rashes; patients experienced only acute Lyme disease which was promptly treated. None of the patients were remarked as being part of the 10% of patients with acute Lyme disease who experience early antibiotic failure, either.[13]

The study participants fit the characterization of the majority of Lyme disease patients who successfully recover from Lyme disease with early treatment - but it does not characterize those patients who do not.

Conversely, if one supports a model of post Lyme disease syndrome, this study won't provide evidence either way as to whether or not this is the case:

None of the patients in this study were reported on followup after a six month interval after any EM rash and subsequent treatment as having developed symptoms indicative of post Lyme disease syndrome. None of the patients were remarked upon as having any particular HLA-DR associated with the development of antibiotic refractory Lyme arthritis - or any potential marker for post Lyme disease syndrome.

If patients have been symptom-free between episodes, this suggests that early treatment aborted the possibility of more serious infection, that patients had a genetic background which made it less likely they would develop antibiotic refractory Lyme arthritis, and/or perhaps early treatment in this small group led to avoidance of post Lyme disease syndrome as well.

Things I Ponder:

  • The good news: If the results of this study can be extrapolated to a larger patient base, early treatment of Lyme disease as soon as one sees a new EM rash is more likely to lead to a positive outcome for the patient.
  • The bad news: This study says nothing about patients who either neither see a tick bite nor get a rash yet begin show other clinical signs of Lyme disease. Doctors have no easy way of diagnosing these patients and current IDSA guidelines do not cover management of such patients.
  • Patients were treated during early to early disseminated infection, when they were most likely to have a positive outcome from antibiotic treatment regardless of the genotype found in their samples.
  • There is no information provided about the health and quality of life of enrolled patients. Do they have any preexisting conditions? Have they ever been diagnosed with any condition with symptoms which overlap with those of Lyme disease? How does one make the distinction between these conditions and any symptoms associated with any stage of Lyme disease outside of an EM rash?
  • The timing, method, and duration of antibiotic treatment for each patient for each episode was not disclosed. Did all patients receive a course of oral doxycycline, or did some with more disseminated infections receive IV Ceftriaxone? This could have an impact on having a positive post-treatment outcome.
  • Regardless of which treatment patients received, how can family and urgent care doctors apply the data from this study to their practice? Hopefully they will see an EM rash and treat patients immediately, but unfortunately this does not always happen in clinical practice as not all EM rashes are properly diagnosed. (e.g. ringworm, eczema, etc.)
  • If infections had advanced past the early stage, I wonder which genotypes would have been found in other sample types had they been taken (synovial, CSF, other tissues). Would they have matched earlier research in previous papers or would they have been different?
  • Over time, is there a change in the kind of genotypes which infect human hosts? Do these genotypes have a "competitive" nature? How much lateral gene transfer occurs?
  • This study applies to the northeastern United States and to infections from Ixodes scapularis ticks. It does not apply to tick bites from Lone Star ticks, which are beginning to outnumber Ixodes scapularis ticks in some areas of the northeast and may carry different infections.
  • The public needs to be reminded that different ticks can carry different infections and look for other symptoms of those which may not be EM rashes.
  • Babesiosis and Rocky Mountain Spotted Fever are two other infection which come to mind where prompt treatment is necessary.
Well, this is what came to mind after reading this study.

Any questions? Comments?

Next up: Reviewing Dr. Steere's accompanying editorial...

1) Dr. Jorge Benach. Presenting at SB Southampton Dean's Lecture Series. Video posted Apr. 20, 2010. Approximate Timestamp: 40:20. "Multiple EM rash is sign of disseminated Lyme disease and requires IV or parenteral antibiotics."
2) Columbia University Lyme and Tick-borne Diseases Research Center, Downloaded November 21, 2012.
3) Strle K, Jones KL, Drouin EE, Li X, Steere AC. Borrelia burgdorferi RST1 (OspC Type A) Genotype Is Associated with Greater Inflammation and More Severe Lyme Disease. Am J Pathol. 2011 Jun;178(6):2726-39.
4)Wormser GP, Brisson D, Liveris D, et al. Borrelia burgdorferi genotype predicts the capacity for hematogenous dissemination during early Lyme disease. J Infect Dis 2008;198:1358-1364
5) Wormser GP, Liveris D, Nowakowski J, et al. Association of specific subtypes of Borrelia burgdorferi with hematogenous dissemination in early Lyme disease. J Infect Dis 1999;180:720-725
6) Seinost G, Golde WT, Berger BW, et al. Infection with multiple strains of Borrelia burgdorferi sensu stricto in patients with Lyme disease. Arch Dermatol 1999;135:1329-1333
7) Liveris D, Varde S, Iyer R, et al. Genetic diversity of Borrelia burgdorferi in Lyme disease patients as determined by culture versus direct PCR with clinical specimens. J Clin Microbiol 1999;37:565-569
8) Jones KL, Glickstein LJ, Damle N, Sikand VK, McHugh G, Steere AC. Borrelia burgdorferi genetic markers and disseminated disease in patients with early Lyme disease. J Clin Microbiol 2006;44:4407-4413
9) Wang IN, Dykhuizen DE, Qiu W, Dunn JJ, Bosler EM, Luft BJ. Genetic diversity of ospC in a local population of Borrelia burgdorferi sensu stricto. Genetics 1999;151:15-30
10) Dykhuizen DE, Brisson D, Sandigursky S, et al. The propensity of different Borrelia burgdorferi sensu stricto genotypes to cause disseminated infections in humans. Am J Trop Med Hyg 2008;78:806-810
11) Wei-Gang Qiu, John F. Bruno, William D. McCaig, Yun Xu, Ian Livey, Martin E. Schriefer, and Benjamin J. Luft. Wide Distribution of a High-Virulence Borrelia burgdorferi Clone in Europe and North America. Emerg Infect Dis. 2008 July; 14(7): 1097–1104.
12) Strle K, Jones KL, Drouin EE, Li X, Steere AC. Analysis of Borrelia burgdorferi Genotypes in Patients with Lyme Arthritis: High Frequency of RST 1 Strains in Antibiotic-Refractory Arthritis. Am J Pathol. 2011 Jun;178(6):2726-39.
13) Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006;43:1089-1134

Additional Resources:
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Monday, November 19, 2012

0 CO Comments on "The Pseudoscience of Chronic Lyme"

During the weekend, Ed Yong, who writes for Discover magazine's Not Exactly Rocket Science blog, of alerted me on Twitter to Cassandra Willyard's blog post on The Last Word on Nothing blog - "The Pseudoscience of Chronic Lyme". Not wanting to pass up the opportunity to comment on some journalists' bungling of how to interpret the significance of the New England Journal of Medicine (NEJM) published study, Differentiation of Reinfection from Relapse in Recurrent Lyme Disease, I decided to stop by and read what Cassandra and others had to say and leave a few comments.

So far, commenters are asking good questions and pointing out some logical oversights in what we have read, which is constructive.

I don't know that I recommend it for casual reading for a number of chronic Lyme disease patients, though - particularly if you are in a headspace where you are currently very angry about your condition being treated dismissively and can't hold up to reading anything which is skeptical about the existence of chronic Lyme disease. But I will say that if you can handle it, it might be worth it to stop by and periodically read the comments.

So far, I've left two comments on Cassandra's blog in response to her original post and another commenter:

"I’ve been following the issue of chronic Lyme disease closely for a number of reasons, and anecdote aside, think that the situation surrounding the diagnosis and treatment of Lyme disease and other tickborne diseases is more complex than most of the media has led the public to believe.

I hear that Lantos – like Dr. Lawrence Zemel of the Infectious Disease Society of America – has more or less stated that half of those patients who claim they have chronic Lyme disease have no evidence of having prior or active Lyme disease. Lantos stated, “Only 7–31% had active Lyme disease and 5–20% had previous Lyme disease,” he writes. “Among the remainder, 50–88% had no evidence of ever having had Lyme disease. Most of these patients had either an alternative medical diagnosis or a functional somatic syndrome such as chronic fatigue syndrome or fibromyalgia.”

If this is in fact the case, then we are still looking at up to 51% of the patient population in this group as either having had Lyme disease or currently having it – meaning that up to little more than half of patients’ persisting symptoms do correlate with evidence of having Lyme disease.

It is this population of which I am a part of, having had a textbook case of Lyme disease – known tickbite in endemic area, an EM rash, flu-like illness, severe joint pain and swollen lymph nodes – the whole nine yards – only to be followed by years of ongoing symptoms I did not have pre-infection.

So, when someone brings up the pseudoscience of “chronic Lyme disease”, understand that I might get a little testy because it seems almost inevitably, the cases which are highlighted in skeptical discussions are those Lantos states do not have evidence of Lyme disease. Whether that is accurate or not, what about the rest of us? (Side note: chronic fatigue syndrome and fibromyalgia are problematic diagnoses in their own way, too, as they are of unknown etiology.)

I want to know as much as the next person exactly what has led to persisting symptoms. After doing the research on my condition to the extent I have, I’m coming to the conclusion that more research is necessary. I am skeptical about their being “sides” to this debate in the first place and also think science has not come to a full understanding about the process behind why we have persisting symptoms.

Embers et al’s recent study on persistence of Borrelia burgdorferi after antibiotic treatment in Rhesus macaques brings up the question of persistent infection after antibiotic treatment. More research is required on this, and persistence studies such as an NIH-NIAID xenodiagnosis study where patients with chronic Lyme disease are bitten by lab-raised ticks in order to see if they pick up the infection are underway. On the autoimmune angle for finding cause, Bockenstedt recently published a paper showing gfp concentration of Borrelial antigens in tendon* tissue in mice, and the hypothesis is spirochetal antigens cause persisting symptoms long term. See this Research Blogging blog post for more info:

So one cannot avoid that persisting symptoms after initial infection and treatment or delayed treatment is an issue; the research is there and being conducted on it.

But in the meantime, people are suffering, and voting with their feet: The vast majority of patients in my situation think there is something to the persisting infection hypothesis, and treat with long term antibiotics. A number of them recover and report improvement in symptoms while on treatment.

Yes, it is anecdotal – true. And it doesn’t support the outcomes of some of those small clinical trials which were conducted. But perhaps instead of dismissing them, someone could step in and collect the data on these patients (with their consent, of course) based on how they are currently being treated, what the patient base is and common factors of different subpopulations, and so on – and see if any commonalities float to the top? This could be informative, to study patients who have made the decision to accept this treatment and see how they fare."

And the second comment:

While I have not read the full text of the study yet, I agree that your logic path is one I traveled as well. An EM or “bull’s eye” rash is a key part of the case definition for acute Lyme disease – however, it’s not always present with infection, nor do all EM rashes signal the presence of infection.

Much of the media’s write-up on this study has conflated the existence of reinfection with the nonexistence of a chronic condition connected with Lyme disease – but it has also left out a huge chunk of the story about the significance of EM rashes in Lyme disease infection.

Dr. Jorge Benach of Stonybrook University has stated that if multiple “satellite” rashes show up weeks to months after initial infection, that the bacteria has disseminated. This may mean the patient needs a different course of treatment at this stage, so new rashes in this situation are important to separate from new EMs from a new infection.

Dr. Benjamin Luft has been doing extensive mapping of the genetics of different strains of Borrelia burgdorferi and has discovered some strains create a rash but no infection, some create a rash and infection, and some create no rash and infection. These strains can have varying targets within the body; varying levels of virulence.

And not long ago, Horizon Press published a book, “Borrelia: Molecular Biology, Host Infection, and Pathogenesis”, and it mentions big gaps in patient management around EM rashes: Some people who were screened to be subjects in studies were seropositive for Lyme but have never had ANY symptoms – whereas others went on to develop a case of late stage Lyme disease. (See pp. 501-502)

This is problematic for patients and doctors alike, who may have difficulty diagnosing the cause for the patients’ symptoms with no prior history/evidence of Lyme disease.
(Serology might help – but you have to suspect Lyme disease first.)

(As an aside, you might want to check out this discussion on Lymenet Europe: – if only because of the references offered.)

So, I am concerned about the emphasis on rashes and think either one has to suspect Lyme disease based on other symptoms and potential exposure to ticks – or we need better testing… Solid direct detection tests would be great, but we don’t have one yet. I’m waiting to see what GMU does with its nanotrapping test development… It’s antigen based; hopefully superior to existing serological tests. But again: First one must suspect Lyme, and if there is no EM rash present, where do you begin?

* That should have been "joint" tissue, not "tendon".

When I wrote these comments for their intended audience, my goal was to focus on what by their standards would currently count as evidence they relied on in order to focus on the relevance of erythema rashes in infection. I avoided discussion of other issues I could have gotten into - such as the accuracy of early serological testing and differences in antibody response during infection - because my focused comment was already long and thought these topics were not as closely related.

One thing that has changed between the time I posted these comments and now: I now have a copy of the full text of the NEJM reinfection paper. So I am in the process of reading it, examining the data, and seeing how the authors correlate their findings with chronic Lyme disease. More later...

Edited to Add: When I talk about being skeptical about there being "sides" to the debate, what I am really meaning to say is that while two sides have developed over time, the only side that really matters is the truth.

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Thursday, November 15, 2012

4 Do Not Conflate Reinfection With Absence Of A Chronic Condition

It's been a busy day for Lyme disease in the media today. And for me, too, as I have been trying to do some education (translation: damage control) regarding the inaccuracies which were reported concerning the findings from small study on Lyme disease that was recently published in the New England Journal of Medicine (summary only; full text behind pay wall).

With a sample size of 17 participants, the study advanced the idea that most patients who have new erythema migrans (also called "bull's eye") rashes have been reinfected and do not have a previous relapsing infection. Bacteria sampled from the new rashes and run through PCR do not match bacteria from old rashes from a previous infection - therefore, patients have been reinfected.

In and of itself, these findings are not problematic. And they make sense, knowing what is known about EM rashes and immune responses to Borrelia burgdorferi. It is only one small study, and I don't see it as earth shattering nor does it tell anyone everything there is to know about Lyme disease.

But what follows is problematic: A number of online news articles stated that this outcome provides evidence that Chronic Lyme Disease and (unwittingly, in some cases either implied or by extension) Post Lyme Disease Syndrome do not exist.

Now, while most Lyme disease patients with persisting symptoms support a chronic infection model, there may be some people who develop an autoimmune condition such as Post Lyme Disease Syndrome due to having had Lyme disease. I simply don't know, and think more research is required on this subject. But either way, the conflation of this small study's findings with the nonexistence of a chronic condition is erroneous.

Even by the IDSA's standards, some interpretations of Dr. Allen Steere's editorial which accompanied the study (briefly blogged about here on the NEJM) seemed to get it wrong. On one hand, Dr. Steere acknowledges persisting symptoms and he states that "infection-induced autoimmunity, retained spirochetal antigens, or both may play a role in this outcome." And on another, a number of journalists seemed to gloss over this statement and not mention it - alongside stating or implying that a new, acute infection is the only reason patients get ongoing or new symptoms.(Um, late stage untreated neuroborreliosis, anyone? Coinfections? These things can happen on occasion...)

This is incorrect, and so I've tried to correct this inaccuracy in reporting by responding to media outlets online. I've spent a good part of today looking online for articles which I could respond to about this issue, and noted that several news outlets and online magazines either do not allow comments on posts related to this topic or require one to post comments using Facebook and other services which not everyone uses. But I posted to as many places as I could, and wrote more or less the following comment in most locations:

"This is one of several articles I have seen which conflates this study on new rashes and new infection with the issue of chronic Lyme disease or persisting post-treatment symptoms - when the two issues are distinctly separate ones.

Even if one does not believe that Lyme disease can be a chronic infection (which in the scientific world it continues to be a matter of debate if a study like Dr. Embers' Persistence of Borrelia Burgdorferi after antibiotic treatment in Rhesus Macaques has been published recently and the NIH-NIAID is funding a xenodiagnosis study to see if human hosts with chronic Lyme disease can pass their infection onto lab-raised ticks - hardly a sign the debate has been resolved), the IDSA itself recognizes that a percentage of patients who were treated for Lyme disease go on to have persisting symptoms for months to even years after initial infection. Their organization thinks it is possibly autoimmune and call it Post-Lyme disease syndrome; there are now proteomics studies that have been done which provide markers for this condition.

Whichever model of persisting symptoms you support, it is incorrect to associate this one study with disproving the existence of either a chronic infection or post-infection autoimmune condition in patients with ongoing disease and disability since contracting Lyme disease.

I think that one also has to be careful about the utility of the EM or bulls' eye rash in proper diagnosis of Lyme disease in general: According to Dr. Jorge Benach of Stonybrook University, if more satellite rashes erupt after the initial rash (usually within weeks to months) the infection has disseminated. Also, not all cases of Lyme disease present with an EM rash, and research by Dr. Benjamin Luft has shown that some strains of Borrelia which disseminate with a rash do not cause disease and some without rashes do cause disease.

One study like this is not enough to set the course for Lyme disease, which is an emerging infectious disease which requires more research."

In other words, as it bears repeating: The rash is not the disease.

I really don't know what else I can say in response to these articles. I've made my point where I can, short of writing letters to the editor.

Other than this, of course, I recommend responding in your own way to these articles online and cite research that has been published or is currently in progress on Chronic Lyme Disease, Post Lyme Disease Syndrome, or both. And if you're a patient, inform people about the science that is out there and let them know you are in the 10-20% of patients who has persisting symptoms after initial infection with Lyme disease. You exist. Your condition is real.

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Friday, November 9, 2012

2 New Lyme Disease Detection Test For All Stages Of Infection

For all those observing today: Happy Carl Sagan Day! For everyone else: Happy New Lyme Test Day! I say this because today a new blood test for the detection of all stages of Lyme disease has been launched.

In a press release, Boulder Diagnostics reported the European market launch of the CE marked SpiroFind in vitro diagnostic test for the detection of active Lyme Borreliosis. The makers of the novel SpiroFind test claim it can detect active Lyme Borreliosis through all stages of disease from early disease to late and persistent manifestation.

The test is based on measuring the cellular immune response to a specific challenge with the Borrelia organism. The effectiveness of the SpiroFind test was confirmed in a clinical study at the Radboud University* Nijmegen Medical Centre, which is submitted for peer-reviewed publication and for presentation at the ECCMID conference in Berlin, Germany in April, 2013.

“We are proud to offer this important new tool for the correct diagnosis of Lyme disease”, comments Dr. Wolfgang Pieken, CEO of Boulder Diagnostics Inc., and adds “the SpiroFind test is the first method to query the trained immunity to Borrelia infection as a signal for active disease”.

“At our clinical laboratory in Mellrichstadt, Germany, we now accept whole blood samples for testing by the SpiroFind method,” states Dr. Anton Waldherr, laboratory physician of Boulder Diagnostics Europe GmbH.

Professor Leo Joosten of Raboud University has been collaborating with Boulder Diagnostics and has worked on a project by Oosten et al which may have shaped the design of this test, "The interaction between NOD2-autophagy pathway and inflammasome activation determines the chronicity of Lyme arthritis" - see this paper's full text on Pubmed. The reason why some patients may develop persisting symptoms is because of a defect in their immune system.

Looking at Dr. Joosten's long list of publications on immune factors involved in infection, one can see that he has accomplished a lot of research on cytokines, Toll-like receptors (TLRs), and biomarkers of infection and inflammation.

It also should be noted here that Raboud University has also been involved in clinical studies on the use of long term antibiotic treatment for chronic Lyme disease as the sponsor of the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) - perhaps subjects of this study were also used to help assess this new test?


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