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

[alkt]

I am really lost and talking to self. Deep pain does that?

did you go to casualty even a junior doc should be able to recognize a broken arm .

 

[Izola]

did you go to casualty even a junior doc should be able to recognize a broken arm .

hi! You would think!!

 

[BurnA]

Yes, to clarify, I doubt infection causes autoimmunity more than very rarely, but I think ME presenting as an infection may be autoimmune. If the effect of the autoimmune response is to make the person react excessively to viruses then the first sign of the auotimmunity will be a 'viral illness'. Something like this happens in lupus. The effect is to make the patient unable to defend themselves against bacterial or fungal infection so the lupus may present as severe sepsis.

One of the features of my onset was that the triggering virus lasted for about 2-3 weeks and then I felt absolutely fine for 2-3 days before being hit by me/cfs overnight. ( I did a 100k cycle and felt 100% and then 3 days later I couldn't get out of bed ) I have read anecdotal similar stories where people are hit with something then feel fine again but then ( very) soon after develop cfs/me. I am not sure how prevalent this is but it doesnt seem too uncommon.

I was wondering if you have heard of this type of onset and if so you have any explanation for it ? Just curious because if there was autoimmunity present before a trigger would there be a lull period? Perhaps it's not specific enough to comment but curious if others observed this also ?

 

[Jonathan Edwards]

One of the features of my onset was that the triggering virus lasted for about 2-3 weeks and then I felt absolutely fine for 2-3 days before being hit by me/cfs overnight. ( I did a 100k cycle and felt 100% and then 3 days later I couldn't get out of bed ) I have read anecdotal similar stories where people are hit with something then feel fine again but then ( very) soon after develop cfs/me. I am not sure how prevalent this is but it doesnt seem too uncommon.

I was wondering if you have heard of this type of onset and if so you have any explanation for it ? Just curious because if there was autoimmunity present before a trigger would there be a lull period? Perhaps it's not specific enough to comment but curious if others observed this also ?

I have heard this story several times and it sounds as if it is a real pattern worth thinking about. The easiest explanation would be that the onset of ME has a mechanism analogous to autoinflammatory disorders like reactive arthritis or Reiter's syndrome where the symptoms of infection are often gone several days before the disease appears. These autoinflammatory syndromes are precipitated by intracellular infections - usually bacterial, which may be important.

If the subsequent ME was autoimmune and the autoimmune tendency to over-respond to infection was already there then I agree that a gap would be odd. But if the over-response links in to the anamnestic antibody response at around 15 days post infection then it would still be possible. My suspicion is that some ME is autoimmune and some autoinflammatory but I am only speculating. If so then any rule would apply some times and not others, which makes things so difficult.

 

[BurnA]

I have heard this story several times and it sounds as if it is a real pattern worth thinking about. The easiest explanation would be that the onset of ME has a mechanism analogous to autoinflammatory disorders like reactive arthritis or Reiter's syndrome where the symptoms of infection are often gone several days before the disease appears. These autoinflammatory syndromes are precipitated by intracellular infections - usually bacterial, which may be important.

If the subsequent ME was autoimmune and the autoimmune tendency to over-respond to infection was already there then I agree that a gap would be odd. But if the over-response links in to the anamnestic antibody response at around 15 days post infection then it would still be possible. My suspicion is that some ME is autoimmune and some autoinflammatory but I am only speculating. If so then any rule would apply some times and not others, which makes things so difficult.

Thanks. As usual I want to ask many more questions, but for now ill just ask why bacterial infection may be important ? I understand the relationship to Reiters or reactive arthritis but I have never heard it in terms of me/cfs before. Could It be an analogous situation?

A more broad thought....If there are two ( or more) types of ME/cfs then does it seem even odder that so little is known or understood ? Would you have expected that one type would be understood by now - I mean there are double the chances of finding something if there are two types ? I know it might make it harder in some sense because any data set would be muddled but what are the chances that one disease can have multiple causes yet so little is known about any of the causes. My impression is that current or past searches for a biomarker were or are broad based and therefore could identify either or any type of the disease ?
Two elusive diseases wrapped up in one enigma.

 

[Valentijn]

@Jonathan Edwards - To make things a little more interesting, I think it's likely that I had shorter and milder episodes of PEM in the years prior to the sudden onset of chronic and severe symptoms.

So I would have months where I couldn't pass a stupid aerobics or walking class at University, and was getting "sick" on a weekly basis, yet could retake the class a few months later with no problem. Similarly with a martial arts class. Sometimes I made good progress, and sometimes I got the "flu" every week and had to drop it for a while. But never any noticeable impairment when not doing exercise or martial arts classes. And in retrospect, I think those periods of recurring illness were PEM.

Prior to chronic symptoms starting 5 years ago, I was doing a lot of walking to classes, between buses and a train, often at a very fast pace. No problems. Then I had a nasty flu where I made it to a few classes at the end of a course for a week, followed by a week of blessed rest after the course ended. When courses started up a week after that week of rest, I thought I was over it, but my legs started burning like crazy when walking. And instead of that receding after a few days of my usual amount of walking, more and more noticeable symptoms came on, and with progressively more severity.

Does that fit with an autoimmune profile? My triggering infection may have been Lyme, about 10 years prior to sporadic PEM, and 20 years prior to chronic ME/CFS. And the illness prior to the chronic onset did seem like a typical nasty flu.

 

[slysaint]

I think genetics is becoming a bit of a 'get out of jail free card' to explain the cause of a number of illnesses.
I imagine everyone is genetically predisposed to contracting something, but it doesn't necessarily mean they will get it.
In terms of my own onset of ME, I'd had a bad chest infection, then pneumonia for about a month, lots of antibiotics. Felt better, went back to work but only lasted a day. I would describe the very early stages like a dodgy electrical switch which would flick on and off without warning. Then one day it went off and never came back on again. Don't know how this would fit into any of these theories.
I recently saw a documentary about people who had suffered brain injury and although physically some had made almost complete recoveries, they were still left with symptoms the cause of which could not be identified. Some of which sounded a lot like ME symptoms. Again, I'm not sure how this fits in with anything!

 

[Jonathan Edwards]

@Jonathan Edwards - To make things a little more interesting, I think it's likely that I had shorter and milder episodes of PEM in the years prior to the sudden onset of chronic and severe symptoms.

So I would have months where I couldn't pass a stupid aerobics or walking class at University, and was getting "sick" on a weekly basis, yet could retake the class a few months later with no problem. Similarly with a martial arts class. Sometimes I made good progress, and sometimes I got the "flu" every week and had to drop it for a while. But never any noticeable impairment when not doing exercise or martial arts classes. And in retrospect, I think those periods of recurring illness were PEM.

Prior to chronic symptoms starting 5 years ago, I was doing a lot of walking to classes, between buses and a train, often at a very fast pace. No problems. Then I had a nasty flu where I made it to a few classes at the end of a course for a week, followed by a week of blessed rest after the course ended. When courses started up a week after that week of rest, I thought I was over it, but my legs started burning like crazy when walking. And instead of that receding after a few days of my usual amount of walking, more and more noticeable symptoms came on, and with progressively more severity.

Does that fit with an autoimmune profile? My triggering infection may have been Lyme, about 10 years prior to sporadic PEM, and 20 years prior to chronic ME/CFS. And the illness prior to the chronic onset did seem like a typical nasty flu.

That seems to fit with real life Valentijn! Once stories get more than a little bit complicated I think you start getting too many possibilities to choose.

 

[BurnA]

If the subsequent ME was autoimmune and the autoimmune tendency to over-respond to infection was already there then I agree that a gap would be odd. But if the over-response links in to the anamnestic antibody response at around 15 days post infection then it would still be possible. My suspicion is that some ME is autoimmune and some autoinflammatory but I am only speculating. If so then any rule would apply some times and not others, which makes things so difficult.

2nd question
How would autoinflammatory be consistent with this gap or lull period ? If an infection lasts a few weeks why would an autoimflammatory response be delayed until after this ?

Perhaps this has been discussed elsewhere but there seems to be a percentage of patients whose me/cfs develops post ebv. I assume there is no direct link to autoimmunity in these cases therefore these could fit into an autoinflammatory subset. Because some of the responders in the phase 2 trial associated ebv with onset, does this add up ... Have I got it wrong or is it just a case of too many unknowns ( as always !)

 

[Marco]

I recently saw a documentary about people who had suffered brain injury and although physically some had made almost complete recoveries, they were still left with symptoms the cause of which could not be identified. Some of which sounded a lot like ME symptoms. Again, I'm not sure how this fits in with anything!

There's something called post-concussion syndrome where a range of symptoms persist long after the mild traumatic brain injury 'should have' healed. The symptoms (and the reactions of the medical profession) are very similar to ME/CFS.

 

[BurnA]

My suspicion is that some ME is autoimmune and some autoinflammatory but I am only speculating. If so then any rule would apply some times and not others, which makes things so difficult.

I know I ask too many questions.
However if two or more subsets existed, would you have expected it to be easier to group patients per symptoms or would such a large overlap of symptoms exist. I know POTS exists in only a subset of patients, and perhaps symptoms of IBS and brain fog to some extent, but it seems PEM and unrefreshing sleep, amongst others, are across the board. To a layperson, would it be easier to group patients into symptom groups to study. Seems too obvious that this wouldn't have been done already, but if we are talking subsets surely this might be of benefit ? I would like to think blood samples for biobanks have this detail but maybe it isn't as useful as I imagine.

 

[msf]

We´ve had this discussion multiple times (probably earlier in this thread too), but I think the Reactive Arthritis analogy is a dangerous one. Here are two recent studies that provide further evidence that Reactive Arthritis is caused by the persistence of the triggering organism:

http://www.ncbi.nlm.nih.gov/pubmed/25624153

http://www.ncbi.nlm.nih.gov/pubmed/25442760

The second study replicates Carter´s findings that antibiotic treatment can cure Chlaymdia-triggered Reactive Arthritis.

 

[halcyon]

One of the features of my onset was that the triggering virus lasted for about 2-3 weeks and then I felt absolutely fine for 2-3 days before being hit by me/cfs overnight. ( I did a 100k cycle and felt 100% and then 3 days later I couldn't get out of bed ) I have read anecdotal similar stories where people are hit with something then feel fine again but then ( very) soon after develop cfs/me. I am not sure how prevalent this is but it doesnt seem too uncommon.

This is extremely common and is why Dr. Hyde describes ME as an acute onset biphasic disease. He notes that this is the exact same pattern that occurs in those with poliomyelitis.

 

[BurnA]

This is extremely common and is why Dr. Hyde describes ME as an acute onset biphasic disease. He notes that this is the exact same pattern that occurs in those with poliomyelitis.

This is interesting. I am curious if or how would it relate to the immune system ?

 

[halcyon]

This is interesting. I am curious if or how would it relate to the immune system ?

I imagine those with an appropriate immune response to the infection don't go on to the second phase, i.e. abortive poliomyelitis.

 

[Forbin]

Regarding the "lull" between infection and the sudden development of ME symptoms, I found this at the NORD (National Organization for Rare Disorders) website. The article was written with the help of Leonard Jason, but I don't know if he contributed to this section.

Some cases of ME may develop in two phases (biphasic). The first phase is an acute primary infection phase. Affected individuals may have an infectious disease with an incubation period of approximately four to seven days. Other cases may follow a more gradual onset. Closely following this initial phase is a second phase known as the chronic phase. This second phase usually occurs two to seven days after the initial infection and is characterized by measurable widespread (diffuse) changes in the central nervous system.
https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/

I came down with a flu that was very severe for the first couple of days and then went away over the course of about a week. Other than the initial severity, it seemed a pretty standard case of the flu. There then followed a lull, during which I felt fine and even went on a long and strenuous hike with a friend. On a couple of brief occasions during the lull, I experienced a subtle sort of visual distortion - sort of as if viewing the world through a curved piece of glass. These sensations were fleeting. I thought I was imaging things.

About 18 days later, I experienced the sudden onset of ME symptoms, which began very distinctly with a "dizzy spell" that would not go away. I imagine that the earlier visual distortions were some sort of precursor to this "dizziness." Once it began, other ME symptoms showed up over the course of a couple of weeks and then worsened significantly over the following months. In my case, ME started like a switch being thrown, but the full scope took some time to develop.

Although I realize that it is not universal, I just have a feeling that this "lull" is telling us something. I just wish I knew what.

 

[halcyon]

Although I realize that it is not universal, I just have a feeling that this "lull" is telling us something. I just wish I knew what.

I think it's pretty clear. It's the time it takes for the initial viremia to resolve but the virus is not gone, instead it just takes a bit longer for it to reach the CNS and establish an infection there. I had the same pattern that you described. Initial severe GI infection, then a lull, then onset of vertigo/vestibular neuritis, then a lull, then full onset of remaining ME symptoms.

 

[Sidereal]

There's something called post-concussion syndrome where a range of symptoms persist long after the mild traumatic brain injury 'should have' healed. The symptoms (and the reactions of the medical profession) are very similar to ME/CFS.

I suspect this is a case of each medical specialty coming up with its own name for the ME/CFS elephant. Although the infectious trigger is the most common, some cases are triggered by mild TBI, surgery, trauma, vaccination, overtraining etc. Some are gradual onset without an obvious trigger. This is why I struggle with the virus hypothesis. I think a hypothesis needs to be able to explain all these observations, not just cherry-pick the viral onset subset and ignore the others.

 

[rosie26]

I experienced the sudden onset of ME symptoms, which began very distinctly with a "dizzy spell" that would not go away. I imagine that the earlier visual distortions were some sort of precursor to this "dizziness." Once it began, other ME symptoms showed up over the course of a couple of weeks and then worsened significantly over the following months. In my case, ME started like a switch being thrown, but the full scope took some time to develop.

The dizziness you speak of here was the same for me when I experienced the beginning of my mild ME. I had two days of extreme dizziness, never had felt anything like it before. I had to leave a class where I was studying part time because I felt so unsteady and unbalanced even sitting in a chair. Concerned I left class early and visited a doctor in town before I went home.Two days later I went down with a very hot sore throat and flu-like cold. This was the beginning (over 20 years ago) of the first appearance of symptoms of ME and from there on all ME symptoms worsened, then I caught a very bad flu in 2001 and I was thrown into severe ME, it felt like this second flu locked me in ME completely.

Edit. But I think for myself, that it was a bacterial infection thirty years ago when I was 20 years that which is involved in the underlying illness and the flu years later has turned the underlying illness into ME.

 

[SOC]

...some cases are triggered by mild TBI, surgery, trauma, vaccination, overtraining etc.

I'm not sure I agree with this if you are defining ME/CFS tightly -- as with the CCC (well-admininistered) or the ICC. Yes, there may be ME-similar illnesses that include fatigue and neurological problems and were initiated by things like TBI, trauma, or overtraining, but I'm not ready to say those conditions are equivalent to ME/CFS. I suspect that many of those cases are wastebasket diagnosis cases -- people with unexplained fatigue and some other symptoms are given the CFS diagnosis because doctors can't explain the symptoms.

Of course we don't know for certain what ME/CFS is and we can't separate out different groups until we have biomarkers that can distinguish them, so I won't say it's absolutely not true that ME/CFS can be triggered by TBI or overtraining. But I'm certainly not taking it as a given.