Tracking my efforts to beat Myalgic Encephalomyelitis (ME), aka CFIDS, aka CFS

Tracking my efforts to beat Myalgic Encephalomyelitis (ME), aka CFIDS, aka CFS

Tuesday, July 22, 2014

Minor Differences in Generic Rx's Can Have Major Effects

About a month ago, I mysteriously started experiencing serious stomach pain.  I haven't had significant gut issues since my acute phase, before I changed my diet.  This new pain got to the point where it became unbearable and I couldn't think of much else.

Again, I turned to my daily health chart to see if I could find answers.  The only significant change I noticed near the time of the onset of the stomach pains (four days earlier) was that I had switched brands of generic Valacyclovir.  For more than a year prior, every time I went to the pharmacy, they would dispense a particular generic brand.  This one time, all of a sudden, the bottle looked different and I was given a different brand.  I didn't think anything of it.  I figured all the generic brands were pretty much the same....until 10 days later when I noticed a possible connection on my health chart.

To test whether the new brand was actually responsible for the pain, I took a "holiday" from Valcyclovir for a few days.  The stomach pains subsided.  As soon as I resumed Valacyclovir, the pains returned.

For the past few months, I had been meaning to change pharmacies, so this was the motivation I needed to make it happen.  I switched from a national chain to a local compounding pharmacy.  I told the new pharmacist about my experiences with the different generic brands.  He said it's fairly common. Obviously, he said, the active ingredients in the generic brands are the same, but each generic brand contains different "fillers."

My refill with the new pharmacy was with a third generic brand--one I'd never tried before.  I've been taking the new brand for about a week and it hasn't caused any trouble.  Since that experience, I've searched the internet for further information on this issue, and it appears to be a fairly common problem, not only among brands of Valacyclovir but any type of drug with multiple generic options. The lesson I learned is that, just because a generic drug doesn't agree with me, doesn't mean that drug is off limits.  I may be reacting to an inactive ingredient.  I suppose the only way to find out is to try another generic brand ... or Google it!

Friday, July 18, 2014

Did we just take a HUGE step toward a unified model of ME/CFS?

It seems as if every day there's an article discussing new research findings and treatment theories in the ME/CFS blogosphere.  In the first year or two of my illness, these articles excited me.  I read every single article and blog post about new theories and treatments.

Then, after a while, I started to realize that most often nothing becomes of these promising leads.  We never hear about them again.  In the past year, I reverted to simply skimming the headlines and surmising the gist of most articles.  I look for anything that sounds like a true breakthrough...or anything that "connects the dots" with prior research.

After this year's IACFS Conference, I felt conflicted again.  All the information I'd absorbed sounded so promising, and yet, we still had dozens of different theories, each of which only seemed to explain a portion of the disease.  There was no serious attempt yet to synthesize the various research findings into a unified model.

Here's what I wrote after the IACFS Conference:
The next big breakthrough in ME/CFS research. ... will be the first. 
As sobering as that is, we can't point to any one finding over the last 30 or 40 years that truly qualifies as a "breakthrough."  I'm referring to a breakthrough on the order of the XMRV discovery....had it turned out to be correct.   
We have nothing like that.  So when I read accounts of the IACFS conference, or the daily articles that make the rounds in our blogosphere, I have mixed feelings.  A few dozen dedicated researchers are working on their pet theories and all seemingly churning out important findings.  It all sounds positive...we are surely making "progress"!  Right?
But it raises the question: Is one of the researchers correct, and the others wrong?  I think, almost certainly not. There are too many confirmed physiological abnormalities found in ME/CFS patients that are, by now, beyond debate.  In the immune system alone, there is a constellation of problems, and that's just one part of the disease.  We know with absolute certainty we're dealing with a complex multi-system disorder. And so each of these dedicated ME/CFS researchers is probably focusing on what will turn out to be but a small piece of the puzzle. 
When a true breakthrough finally occurs, it will look like one of two things:  Ideally someone will suddenly discovery the etiological cause--the one event that sets off the long chain of subsequent physical derangements.  Then we'd have a true focus for treatment research. 
But barring such a "homerun" discovery, true breakthroughs will begin to occur when someone with a mind toward the "big picture" starts making connections between the various derangements.... and proving them.  Someone has to start linking these findings in a causal chain so that we can begin to create a comprehensive model of this impossibly complex disease. 
It appears that one of our beloved ME/CFS researchers is finally starting to do just that--to look at the big picture and develop a unified theory.  If you haven't yet read Cort Johnson's article summarizing Dr. Lucinda Bateman's recent pronouncement, you really should.  The one-sentence version is that Dr. Bateman has developed the beginnings of a unified theory, where ME/CFS starts with inflammation in the limbic part of the brain.

It's true that others have proposed general theories before about how everything fits together, but I don't believe it's been done with this level of clarity and confidence -- and by someone who is respected as a leader in ME/CFS research.

I've been a strong proponent on this blog that a unified theory will start and end in the brain--the hypothalamus specifically. (Examples 1, 2)  That of course isn't my theory, but it's the one that always made the most sense to me because it is the only one that could explain all the myriad symptoms and derangements we experience.  Bateman is now saying it's not just the hypothalamus but it's inflammation in the entire lower portion of the brain.  More importantly, she's gone beyond the stage of idle speculation and has actually coalesced the research findings of her colleagues into a well thought-out hypothesis that makes a lot of sense.

What We Need to See Next

Obviously we're still a very long way from solving this disease, but here are a few things I'd like to see happen to push us closer to that goal.

1.  Naturally, the hypothesis needs to be tested... extensively.  This will be a long and expensive process (maybe a decade or more?) but I truly believe that it will be confirmed, if not refined a little in the process.  

2.   The theory needs to be expanded to explain some of the other derangements we see in ME/CFS patients, especially in the immune system.  Dr. Bateman speaks of auto-immunity (overactive immune response).  But what about other aspects of the immune system that are under-active in ME/CFS patients (specifically Natural Killer Cells, and usually, one or more IgG subclasses)?  Any unified model must explain immune deficiencies too.

3.  Where do pro-inflammatory cytokine storms fit?  Are they upstream or downstream of the brain inflammation?  Do the pro-inflammatotry cytokines cause the brain inflammation, or does the brain inflammation lead to immune dysfunction and, thus, cytokine storms?

4.  Of course, it would help if someone could actually explain the external cause of ME/CFS, but I suspect we already know about as much as we'll ever know.  It's generally accepted that there are probably many doorways into ME/CFS: viral, bacterial, stress, traumatic injury, genetics, exposure to environmental toxins.  I think it will be a very long time before we're able to be more specific than that.

5.  Now that someone has developed a credible unified theory that actually makes a lot of sense (in my opinion), and after it's been tested, we've got to ensure widespread support for it from other ME/CFS experts.  We've got to somehow get all or most of these experts pulling in the same direction.  That step would require the concerted effort of an organization like IOM, or it would require one of the big-name researchers like Bateman to become a leader and rally the others behind her (if that's even possible).  This would likely be a very long process too.

6.  After general acceptance among ME/CFS researchers, this new model would expand and gain general acceptance among ME/CFS clinicians, and from there, spread to the greater medical community in general.  True, acceptance in the general medical community seems like a pipe dream now, but if there were a complete model that explained all of our symptoms and could be tested and confirmed, it would gain traction fast.  

(Remember the trajectory that the XMRV theory was on?  Imagine how quickly that knowledge would have spread among the general medical community if the findings had been confirmed.  They'd already be teaching it in medical school).

7.  I believe that only after there's a model of ME/CFS that truly gains acceptance in the general medical community will we ever see the major drug companies take a serious look at this disease and begin to develop drugs, in earnest, specifically for ME/CFS.   

Wild Speculation About the Future

When you consider all those steps, it can be a little discouraging.  Even if Bateman is 100% correct, it could still take as long as 20 to 30 years or more for these steps to occur.  Then again, sometimes progress doesn't occur in a linear fashion.  Progress sometimes builds momentum exponentially.  

Looking at the epidemiology of other diseases, often when one key connection is made, others are made very rapidly afterwards.  Imagine what would have happened had XMRV been confirmed.  Research money would have started pouring into our bare coffers.  Drug companies would have been racing to beat each other to the market with an XMRV anti-viral.  Our small circle of ME/CFS researchers would have likely expanded as other virologists and epidemiologists all over the world would have turned their attention to ME/CFS.  Progress would have accelerated very quickly for us. 

At any moment, we're just one breakthrough away from a rapid acceleration of progress.  Could Bateman's theory be the breakthrough?  Probably not because it's not a research finding...yet.  So far it's just a hypothesis.  But if and when it is tested, I believe it has the best chance yet of any hypothesis we've seen of being the breakthrough.

For now I'm simply glad that someone in a lab coat is finally looking beyond their own pet theory and trying to make sense of what their peers are doing too.  More of that, please!

Monday, July 7, 2014

3 Year Anniversary - Looking Back

Somehow, almost an entire month has passed since my last post.  I'm not sure how that happened.  In the meantime, my 3-year ME/CFS anniversary  has passed.  These so-called "sickiversaries" make me reflect on how I've progressed and changed since first getting ME/CFS.

As I wrote last year, I dreaded the 3-year anniversary because researchers have noticed fundamental differences in the physiology of patients who have been ill with ME/CFS for greater than 3 years.  For example, patients of 3+ years typically have cytokine profiles that are different from newer patients.  I've also read that if a patient has any chance of recovery, they will usually recover within the first 3 years.  After that, the chances of recovery fall significantly.  All this suggests that something occurs at about the 3-year mark that changes the course of ME/CFS for the worse.

For now, however, I am not too worried about having passed the 3 year mark because I have been doing relatively well lately.  It's always easy to brush off these types of concerns when you're doing well, isn't it?  Over the last 2 or 3 months I have been doing well enough that at times I've even wondered, "Am I in remission?"

The answer to that question is an emphatic NO.  Every time that question arose in my head, symptoms would flare and I would be reminded that I am still quite ill in many ways.  But it's remarkable that the question even enters my head sometimes.  During my first and second year, I would have never entertained that thought, even for a second.

As regular readers may know, I keep a daily health chart, and I calculate an average of my overall daily rating at the end of each month.  When I charted my monthly health averages over the past 3 years I saw a very slow and steady rise.  The increase was so slow and steady that it was imperceptible from month to month as I lived through it.  I could only see it after graphing it visually.  But I know that it's real (not simply a shift in my rating sensitivity) when I think about certain activities that I was unable to do two years ago and that I am able to do now.  For instance, I am able to perform maintenance work around the house and garden without much, if any, consequence.

Yet, there are still many signs that I am fundamentally ill, particularly in my immune system:  My natrual killer cell activity is still pathetically low.  My IgG subclass 3 is still low, out of range.  I still have ongoing Candida overgrowth, another sign of a weak immune system.  And I still suffer frequent sore throats.  When these sore throats arise, my tongue swells so badly that it becomes difficult to talk. I still experience shortness of breath on a regular basis, although that symptom has diminished over time.

There are many other symptoms that I still experience regularly--too many to mention here.

Post exertional malaise (PEM) remains a problem, but the threshold of what I can do before I trigger PEM has risen over time.  During my first year, PEM could be triggered simply by standing for too long, or by walking a few hundred yards.  Now I can do most activities of normal day-to-day life without triggering PEM.  However, if I venture into cardiovascular exercise, I will crash with PEM.  (I was reminded of this just last week when I got cocky and decided that I was well enough to handle a bike ride.  Three days later I crashed badly with that unmistakable PEM feeling.  Luckily, the crash only lasted two days.)

So my challenge now is to maintain my current level of health and possibly even give myself a chance to improve further.  The main idea is not to do anything that will make me regress.  That means, I must fight the urge when I'm having a good day to go crazy and do everything, overwork myself.  I have to always remember that blood tests and my own body are telling me that I'm not "OK" even though I may feel OK sometimes.

Some readers will of course want to know how I improved.  This is a really difficult question to answer, and the honest answer is that I don't really know.  I will try to formulate a theory in future posts, but my responses will be educated guesses at best, and I don't think my improvement was attributable to any one treatment.

I continue to believe that improving with ME/CFS is a combination of luck and, sometimes, putting dozens or hundreds of puzzle pieces into place before anything becomes clear.  This disease is simply too complex and multi-factorial to expect much of a difference from one or two treatments alone.  But then again, I've known many patients who have gone to much greater lengths than me to find improvement, and they only got worse for their efforts.

My suspicion is that improvement is often a matter of luck: perhaps it's stumbling on the right combination of treatments, in the right order, to match each of our own unique etiologies.  And even then, sometimes improvements are fleeting.  It's also clear that what works for one patient, usually doesn't work for the next.  We are clearly divisible into subclasses, in my opinion.  Such is the frustrating nature of our disease.