Are Infections Just a Trigger of ME/CFS, or an Ongoing Cause of ME/CFS?

[Hip]

@leokitten
The info you quoted has a few errors:

Relapse/remitting architecture is actually quite rare in ME/CFS, as far as I am aware. @Eeyore says his ME/CFS is like this, and he can get complete remission for a few years, and then the ME/CFS comes back, rather like a multiple sclerosis course of disease; but this is not the normal course of ME/CFS for most people, as far as I am aware. I don't know many people on this forum who are like this.

However, it is certainly likely that some subsets of ME/CFS may have an autoimmune etiology.

Typical onset in mid 30s is now known not to be the full picture. In fact there are two age groups when there is a high incidence of ME/CFS: a first peak in incidence occurs in the age group 10 to 19 years, and a second peak in the age group 30 to 39 years. The first group corresponds to the typical age that humans first acquire Epstein-Barr virus infection, and of course it is known that 9% of all mononucleosis (glandular fever) cases, which is mostly caused by EBV, end up with ME/CFS. Ref: here. So EBV quite likely accounts for the first peak.

More info on ME/CFS age of incidence:

Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008–2012

the chronic infection theory is a red herring and has been investigated for so many years with no answers.

When Dr Chia treated his enterovirus-associated ME/CFS patients with IV interferon, quite a few went into full remission, some for as long as 14 months. The factor that seemed to cause relapse in these people, and throw most of these patients back in ME/CFS, was significant exercise: when these people did things like go on a hiking trip, involving a lot of physical exercise, their disease would then return.

Interferon treatment tends to induce rather than ameliorate autoimmune disorders. So if the ME/CFS in Dr Chia's patients were autoimmune in nature, you might expect the interferon treatment to worsen their condition, rather than temporary cure it. So this is good evidence for a viral rather than autoimmune etiology in these patients.

So I can't see how this full (but unfortunately temporary) remission from ME/CFS via IFN treatment amounts to "no answers". Likewise for the effects of the antiviral / immunomodulator Valcyte, that has produced considerable improvements in many ME/CFS patients.

 

[Mij]

Boy, I would really like to know whether any form of exercise is bad for us even if we don't feel worse from it as long as we don't get PEM.

I felt as though I recovered when I first became ill, but as soon as I went back to work (on my feet a lot) and did any form of exercise I became even more disabled. I never went into any type of remission after that again for 23yrs.

 

[duncan]

I have always heard that a large portion of PWME suffer relapsing/remitting characteristics.

It is interesting - to me, at least - that Borreliosis is usually not characterized as relapsing/remitting by mainstream medicine, but within the Lyme patient community, and by LLMDs, the relapsing/remitting nature of the disease in its tertiary stage is well-known.

I have diagnoses for both, and my symptoms seem relapsing/remitting. Although I am always symptomatic, the degree of intensity can shift, sometimes for weeks or even months. But my symptoms range from bad to very bad. There are days I eagerly await the bad times.

BTW, I have been under the impression that ME/CFS is relapsing/remitting until it isn't, i.e. you flat line to complete bed-ridden status. Kinda similar to MS.

 

[Hip]

I have always heard that a large portion of PWME suffer relapsing/remitting characteristics.

Perhaps you are right; in this paper it says:

In addition, ME/CFS is a chronic, relapsing-remitting disease involving the waxing and waning of symptoms. The majority of studies examining longitudinal changes in disease activity using internationally agreed diagnostic criteria report a relapsing-remitting or progressive pattern of disease in the patients monitored. Recovery from ME/CFS is extremely rare. The average figure reported in studies using 1988 or 1994 Centers for Disease Control and Prevention recruitment criteria is some 4%.

However, apart from @Eeyore's case, I do not recall anyone on this forum who said they have this relapsing-remitting course. Can anyone else think of anyone here on this forum who has relapsing-remitting characteristics?

Many people here report getting better with certain treatments, such as Valcyte, LDN, vitamin B12, etc. However, that is not the same as getting better without any intervention.

 

[halcyon]

Again I think we are totally barking up the wrong tree thinking this is an infectious disease.

I'm curious how you would explain Royal Free, Incline Village, etc. Epidemic autoimmune disease?

 

[duncan]

I want to quickly add that in the Lyme community, when it comes to treating late stage or chronic Lyme, it's more or less accepted that if the abx protocol doesn't cure, some still can affect positive change...But that that positive change will last only until it doesn't. Then, you move on, and you experiment till hopefully you find something that also provides measured relief for a while. Eventually, though, for many, options run out.

While you are experimenting, part of the challenge is knowing when your improvements are due to a given drug or cocktail. You would think this is easy to do. Sometimes it is. But other times, it's not as clear.

At least, that is my experience.

This of course lends to the confusion around resolving the infection vs immune dysfunction debate, and brings us right back to the thread topic. Hopefully.

 

[leokitten]

I'm curious how you would explain Royal Free, Incline Village, etc. Epidemic autoimmune disease?

It was infection triggered autoimmunity, it's a common trigger to autoimmunity we all know that, there will always be a percentage of people who do not recover from the infection and proceed to an autoimmune condition which is ME/CFS.

 

[SOC]

Boy, I would really like to know whether any form of exercise is bad for us even if we don't feel worse from it as long as we don't get PEM.

I felt as though I recovered when I first became ill, but as soon as I went back to work (on my feet a lot) and did any form of exercise I became even more disabled. I never went into any type of remission after that again for 23yrs.

The exercise physiologist at INIM (and others, I believe) think we can exercise as long as it low level, non-aerobic exercise. That would be things like lifting and stretching. Walking works for some if they have sufficient aerobic capacity. The trick is not to overtax the failed aerobic energy system

 

[leokitten]

@leokitten
When Dr Chia treated his enterovirus-associated ME/CFS patients with IV interferon, quite a few went into full remission, some for as long as 14 months. The factor that seemed to cause relapse in these people, and throw most of these patients back in ME/CFS, was significant exercise: when these people did things like go on a hiking trip, involving a lot of physical exercise, their disease would then return.

Interferon treatment tends to induce rather than ameliorate autoimmune disorders. So if the ME/CFS in Dr Chia's patients were autoimmune in nature, you might expect the interferon treatment to worsen their condition, rather than temporary cure it. So this is good evidence for a viral rather than autoimmune etiology in these patients.

So I can't see how this full (but unfortunately temporary) remission from ME/CFS via IFN treatment amounts to "no answers". Likewise for the effects of the antiviral / immunomodulator Valcyte, that has produced considerable improvements in many ME/CFS patients.

This is all anecdotal evidence from Dr Chia from a few patients and therefore useless, sorry he needs to put his money where his mouth is and do a proper randomized clinical trial with IFN to prove if it actually works. I totally hate when ME/CFS clinicians say they did this and that and it worked for people but they never care to spend the effort to prove it to the rest of the scientific community! You want to know why it's because he knows that it won't hold water in a real RCT.

If he actually found a cure or treatment giving remission in most patients then wouldn't we all be running to him lining up for treatment? We aren't because people know in reality it doesn't work.

At least Fluge and Mella saw something so promising and had the courage to put their reputations on the line and put together a bigger and comprehensive set of RCTs to prove if their treatment will work and who it will work for.

That's so much better than Dr Chia's musings on EV. Interesting but useless.

 

[Hip]

It was infection triggered autoimmunity

You are presenting your own personal speculations as if they were fact. You, nor anyone else, has any evidence that the Royal Free outbreak was due to virally-induced autoimmunity.

[infection is] a common trigger to autoimmunity we all know that

Well if you speak to Jonathan Edwards, he will tell you that he has not seen any convincing evidence of infections triggering autoimmunity.

This is all anecdotal evidence from Dr Chia from a few patients and therefore useless

Actually it is not. There are studies showing the benefits of interferon for ME/CFS prior to Chia's interferon work:
alpha-Interferon treatment of patients with chronic fatigue syndrome
Interferon-alpha therapy for patients with chronic fatigue syndrome

You want to know why it's because he knows that it won't hold water in a real RCT.

More personal speculations presented as if they were fact. What's more, your speculations are wrong: Chia writes in his study: "No commercial funding is currently available for a placebo controlled study [on the interferon treatment]". So that is the reason he has not done a RCT on interferon treatment for ME/CFS.

Lack of funding is an issue here. Chia was also unable to get funding for his oxymatrine study.

Chia is extremely keen on other research groups taking interest in replicating his studies, and is in fact quite upset that after 10 years, nobody has yet done so.

If he actually found a cure or treatment giving remission in most patients then wouldn't we all be running to him lining up for treatment? We aren't because people know in reality it doesn't work.

As for interferon as a cure for ME/CFS, did you not note what I said above, which was that interferon is a temporary cure/remission, which knocked back the virus and eliminated ME/CFS for some months, but the virus returns, as do the ME/CFS symptoms.

Since the three month course of interferon treatment costs around $15,000, since there can be major side effects from interferon, and since people only gained a remission that lasted for a few months to around a year, interferon unfortunately turns out to be not a very viable treatment in most cases, and least in in its present form. However, the important thing to realize is that interferon knocked back the virus, and lead to remission.

And that remission cannot easily be explained using an autoimmune model.

That's not to say that there may not be subsets of ME/CFS that are autoimmune in nature.

 

[Woolie]

@leokitten, I was always in favour of the chronic infection hypothesis, but I've started to come round to the view of Jonathan Edwards, Fluge and Mella and the recent autoimmune research too.

Here's the thing that did it for me. Take the example of EBV. Rituximab kills all your B cells, which, if you can chronic EBV, should also knock out all those nasty EBV infected reproducing cells, and youcan rebuild your B cell reservoir afresh. So why does it only work for a few years and the symptoms come back? Got to be something wrong with immune system.

So infection is maybe a consequence, rather than the primary maintaining factor.

 

[Hip]

I was always in favour of the chronic infection hypothesis, but I've started to come round to the view of Jonathan Edwards

The view of Jonathan Edwards is that there may be some ME/CFS subsets that are caused by intracellular infections, and may be other subsets that are due to autoimmunity.

 

[halcyon]

@leokitten, I was always in favour of the chronic infection hypothesis, but I've started to come round to the view of Jonathan Edwards, Fluge and Mella and the recent autoimmune research too.

Here's the thing that did it for me. Take the example of EBV. Rituximab kills all your B cells, which, if you can chronic EBV, should also knock out all those nasty EBV infected reproducing cells, and youcan rebuild your B cell reservoir afresh. So why does it only work for a few years and the symptoms come back? Got to be something wrong with immune system.

So infection is maybe a consequence, rather than the primary maintaining factor.

EBV infects many other cells other than just B cells. Rituximab will do nothing to remove these other reservoirs of infection.

 

[Woolie]

However, apart from @Eeyore's case, I do not recall anyone on this forum who said they have this relapsing-remitting course. Can anyone else think of anyone here on this forum who has relapsing-remitting characteristics?

Yes, I had relapsing-remitting for 25+ years, but in the last 6 months has flattened into consistently bad. There are quite a few others with this profile too, but can't think of their names at the moment.

 

[lansbergen]

EBV infects many other cells other than just B cells. Rituximab will do nothing to remove these other reservoirs of infection.

So does the infection I suspect.

 

[Woolie]

EBV infects many other cells other than just B cells. Rituximab will do nothing to remove these other reservoirs of infection.

Yes, but if you have no more EBV in your system than any normal person (and remember everyone's carrying it), what is the mechanism that allows it to fully take control again?

 

[Sidereal]

Relapsing-remitting ME exists but I think this term is often used incorrectly by people who are actually describing a chronic but fluctuating (i.e. waxing-waning) course where the person is sick all the time but symptoms fluctuate in severity over time, sometimes hour to hour. I think ME for the most part is characterised by an alarming tendency towards chronicity as Ramsay said.

 

[Woolie]

@Sidereal, maybe I'm weird then, but my remissions were complete for the first 25 years. I could even go touring cycling and skiing if I timed it right. These could last months at a time. Relapses were horrible, though, couldn't lift my head our of bed, severe fever, shakes, awful. All flattening out now to persistent, but glad for the 25 years of breaks that I got.

 

[Hip]

Yes, I had relapsing-remitting for 25+ years, but in the last 6 months has flattened into consistently bad. There are quite a few others with this profile too, but can't think of their names at the moment.

Could you fill us in a bit on the nature of your remissions and relapses. I have some questions, if I may:

(1) How long do your remissions and relapses typically last, or is this quite variable? Are we talking months or years? Do the remissions last for around the same length of time as the relapses?

(2) Have you noticed anything that seems to trigger a relapse or remission?

(3) How much difference in your symptoms do you see between the remission state, and the relapsed state? During the remissions, are you more or less free of any symptoms? I am just trying to get a sense of how different the remission state is from the relapsed state. Are these really chalk and cheese?

(4) What the severity level of your ME/CFS during the relapsed state, mild, moderate or severe? (Descriptions of what mild, moderate or severe ME/CFS means can be found in this post).

(5) Compared to other people on this forum, is your ME/CFS different in any way, in terms of symptoms? I am just trying to get an idea if relapsing-remitting ME/CFS might be symptomatically different to the more constant form of ME/CFS. Do you have OI symptoms for example? Do you get PEM? Is there anything at all usually about your ME/CFS symptoms (apart from the relapsing-remitting course).

 

[Hip]

Relapsing-remitting ME exists but I think this term is often used incorrectly by people who are actually describing a chronic but fluctuating (i.e. waxing-waning) course where the person is sick all the time but symptoms fluctuate in severity over time, sometimes hour to hour. I think ME for the most part is characterised by an alarming tendency towards chronicity as Ramsay said.

Yes, I agree. We would need to make a clear distinction between true relapsing-remitting, and the waxing-waning course of regular ME/CFS, which we all experience from week to week, day to day, and sometimes even from hour to hour.

I am presuming that in true relapsing-remitting cases, ME/CFS symptoms will all but disappear for many months or years, and then return will full severity for many months or years.