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

[msf]

I presume by the term trigger you mean something like viral "hit and run" damage to the body, or viral instigation of autoimmunity; and you also mean that once such triggering events occur, they cannot be easily undone; that is, there is a certain irreversibility about a condition or disease that a pathogen triggers.

Umm, Eeyore didn't seem to respond to your definition of trigger and cause, so other people may beusing different definitions to yours. As I stated above, I think the 'damage' theory is a bad one, as it does not explain the ongoing disease process evident in ME. As for the autoimmunity theory, this is a better candidate, but apart from a suggestion from Fluge and Mella about how this might effect endothelial function, I haven't seen any explanations of how this would cause the symptoms of ME. This is why I said that they were non-theories, although I think it would be more accurate to say that the first is a non-theory and the second is a half-theory.

The chronic infection theory, on the hand, is a comprehensive explanation of the symptoms and ongoing disease process present in ME.

 

[msf]

Thanks Halcyon, you said that much better than I did.

 

[Snow Leopard]

That's the problem, I'm not aware of any model that's been put forward to explain what would be happening in the hit and run model, and yet this is the model that seems to be promoted by a lot of people. I don't believe that a disease like ours with daily fluctuations in symptoms and a relapsing/remitting course can be explained by one time cellular damage. I believe it would have to be an ongoing process of cellular damage or dysfunction, provoked by either antigen or autoantibodies, or both. I'm not aware of any disease or dysfunction that is caused by the immune system "just freaking out" without any stimulus, though I don't have a background in medicine.

The hit/run model (in the absence of autoimmunity) requires evidence of organ damage, whether in the body, or brain/spinal cord.

 

[msf]

It also requires an explanation of why ME patient's conditions change over time.

 

[Snow Leopard]

It also requires an explanation of why ME patient's conditions change over time.

This can be related to subtle changes in organ functioning over time. Quite plausible if there is organ scarring...

 

[halcyon]

This can be related to subtle changes in organ functioning over time. Quite plausible if there is organ scarring...

That could explain persistent worsening, but not relapsing/remitting.

 

[Eeyore]

I think that perhaps there are different types of ME, as in MS (not that one can extrapolate, only using it as an analogy). Relapsing/remitting ME is what I have. It doesn't seem to get better or worse over time in general - instead it feels more like I get into a bad relapse, then recover over a time, then bam, back to bad relapse. It's very unpredictable, but occurs over very long stretches of time (e.g. a relapse or remission usually lasts years). During the good years, I'm never 100% - I think that's damage. I think the relapses reflect a general susceptibility to that disease process - not unlike people who tend to get a lot of kidney stones or who have gout and get flareups from time to time, while other people don't ever get these things.

I think someone who gets it once may have a much weaker predisposition, or none at all, and it is a very strong insult that causes it, then they recover (mostly or completely) and don't relapse.

It is, however, possible that the damage caused by initial infection makes the body less able to respond to triggers it encounters on a regular basis, some of which cause relapses.

Re: the term "hit and run" - I don't think it has one meaning, other than to say that what initiates the cascade leading to the chronic illness is not the same as what perpetuates it. It could be perpetuated by autoimmunity, damage to the body, or many other factors. The key idea is that the insult that started it is not continuously active in causing the symptoms.

The bottom line is that we cannot tell for certain just by looking at symptom patterns whether it is a hit and run or not, and whether or not it's organ damage, autoimmunity, genetic defect, other, or some combo thereof. All we can do is speculate for now.

It's possible that Parvo B19 can cause a 1-time ME in some people who don't have much predisposition, but in others, even if the virus is cleared, they might get triggered over and over by other things separate from the Parvo B19. Alternately it may simply mimic ME. Some people recover from organ damage better than others, for many different reasons, including genetics, age, and treatment.

None of the evidence for ongoing infection is convincing. I am not saying it is 100% conclusively ruled out - I am saying I do not see evidence that makes me believe it is likely. I believe it's possible, but very unlikely, that there is chronic infection causing chronic symptoms.

Also the cytokine mix you describe is pretty generic and just represents the body's immune response to pathogens. Also, we haven't shown that those in particular are elevated in ME. They are elevated per Lipkin/Hornig, but not in isolation - more or less everything was elevated, with just a few exceptions, in ME patients in the earlier phase (first 3 yrs or so) of disease. IL-6 correlates highly with CRP - and many (most?) ME patients have normal CRP. I've never had elevated CRP when tested.

 

[Hip]

I don't believe that a disease like ours with daily fluctuations in symptoms and a relapsing/remitting course can be explained by one time cellular damage.

What about the strong link between significant organophosphate exposure and ME/CFS, which studies of Scottish farmers have shown increases the risk of subsequently developing ME/CFS by a factor of 4.

Organophosphates do not accumulate in the body, so cannot be an ongoing cause of ME/CFS symptoms, but are very neurotoxic, so are probably causing a lot of hit and run damage during the exposure period.

I think the 'damage' theory is a bad one, as it does not explain the ongoing disease process evident in ME.

The damage itself does not have to directly cause the symptoms of ME/CFS; the damage might for example prevent proper functioning of the immune system, which then struggles to control infections, and it is the uncontrolled infections which might cause ME/CFS.

 

[halcyon]

Organophosphates do not accumulate in the body, so cannot be an ongoing cause of ME/CFS symptoms, but are very neurotoxic, so are probably causing a lot of hit and run damage during the exposure period.

I haven't read much about toxin mediated ME but I do believe in the link. What I wonder is if toxin ME is completely indistinguishable from infectious ME? Is toxin ME relapsing and remitting in the same way that infectious ME can be?

 

[halcyon]

the damage might for example prevent proper functioning of the immune system

What kind of damage do you propose this could be, and where would it be occurring?

 

[msf]

Hip, that would be hit and run and chronic infection model, then.

 

[msf]

Unless you meant the herpes viruses. Either way, its a half-theory at best, as you didn't suggest a mechanism for how this would happen.

 

[Hip]

I think that perhaps there are different types of ME, as in MS (not that one can extrapolate, only using it as an analogy).

Yes I think a lot of people assume this. @Jonathan Edwards posits (see this post) that some types of ME/CFS may be due to autoimmune processes, and other types due to infection.

But although there could be lots of different ME/CFS causes, each cause might kick off the same central pathological mechanism (like for example the sickness behavior mechanism), which would explain why the disease symptoms are very similar across a broad range of ME/CFS causal factors.

I find the sickness behavior mechanism very interesting, because it is the only theory so far that can neatly explain the end result symptoms of ME/CFS (and in the case of viral etiologies, can also nicely explain how a viral infection in the vagus nerve itself chronically triggers sickness behavior).

I would like to do a bit of brainstorming to see if it is possible to connect the dots, and examine if autoimmune processes might also somehow be able to chronically activate the same sickness behavior mechanism.

If we could do this, you would start to piece together a universal theory of ME/CFS, where different causes each activate the same central pathological mechanism of chronic sickness behavior.

Relapsing/remitting ME is what I have. It doesn't seem to get better or worse over time in general - instead it feels more like I get into a bad relapse, then recover over a time, then bam, back to bad relapse. It's very unpredictable, but occurs over very long stretches of time (e.g. a relapse or remission usually lasts years).

That's very interesting. I think that is fairly rare in ME/CFS though. It does make me think that your ME/CFS might primary involve autoimmune processes, rather than infectious ones, as a relapsing / remitting course I believe is seen in autoimmune diseases.

Although I think my ME/CFS is most likely driven by chronic viral infection, I have experimented with various treatments for autoimmunity, just to see if these would help. They did not help in my case, but then they likely wouldn't if I don't have an autoimmune processes going. One thing I tried was transdermal estriol, at low dose of 0.3 mg daily. This has been shown to be helpful in MS. It is a very weak estrogen, so for short term use there is no worry of feminization effects. You can buy estriol cream quite cheaply.

Also, we haven't shown that those in particular are elevated in ME.

Those cytokines would not have to elevated.

It's just the cytokine IL-1β that would have to be at high levels in close proximity to the vagus nerve. I understand it is IL-1β which the vagus specifically detects, and which then causes the vagus to activate sickness behavior in the brain. Levels of IL-1β could be very high next to the vagus, but blood tests would not pick this up, because IL-1β is a paracrine and autocrine cytokine, meaning that it does not travel very far in the body, and only acts locally.

According to VanElzakker's vagus nerve infection and sickness behavior theory of ME/CFS, it's when these cytokines are chronically produced in very close proximity to the vagus nerve — such as when the vagus nerve itself is chronically infected — that you get a very strong cytokine signal being picked up by the vagus, triggering sickness behavior.

If the chronic low level infection is elsewhere in the body, away from the vagus, the cytokine signal will be too weak to trigger the vagus.

 

[Hip]

What kind of damage do you propose this could be, and where would it be occurring?

Immune system damage was just a specific example to illustrate the general point, which was that hit and run damage may not necessarily cause ME/CFS symptoms directly, but rather set the stage for ME/CFS to appear.


Though in the case of organophosphates, these are known to cause immune damage, so this could indeed conceivably predispose you developing ME/CFS. It may well explain why the risk of ME/CFS increases fourfold after significant organophosphate exposure (ref: here).

My own ME/CFS was preceding by a severe case of organophosphate poisoning (so severe that I developed psychosis, and my genitals stopped producing semen entirely for a year — and God knows what kind of germline genetic damage that caused). After this horrible poisoning episode was over, I soon after caught what appeared from its symptoms to be a nasty enterovirus, and the rest as they say is history. Would I have developed ME/CFS if the organophosphates had not damaged my body beforehand? I will never know, but I do know that these chemicals have been strongly linked to ME/CFS.

 

[halcyon]

Immune system damage was just a specific example to illustrate the general point, which was that hit and run damage may not necessarily cause ME/CFS symptoms directly, but rather set the stage for ME/CFS to appear.

I understand, it just seems like damage of that nature to the immune system should be visible in the form of hypogammaglobulinemia or cytopenia, something of that nature. There are a bunch of different minute immune abnormalities found in ME patients, but none are found consistently in all patients in all studies from what I have read. I believe the only consistent abnormality is the NK cell dysfunction.

 

[Eeyore]

@Hip - I don't think the vagus nerve infection theory is correct. A better explanation is that organophosphates are cholinergics - they inhibit acetylcholinesterase irreversibly. The cholinergic pathways can be permanently damaged from organophosphate exposure.

One way in which the body regulates immune activity and keeps inflammation localized is the cholinergic anti-inflammatory pathway. If you had damage from organophosphates, your body's natural ability to regulate runaway inflammation would have been severely impaired. Thus you could have had a runaway inflammatory process that caused longer term damage.

 

[Eeyore]

@halcyon - I actually don't think there is generally damage to the immune system so much as there is damage to the CNS because of a genetic predisposition to immune dysregulation.

 

[Sidereal]

@halcyon - I actually don't think there is generally damage to the immune system so much as there is damage to the CNS because of a genetic predisposition to immune dysregulation.

What sort of CNS damage?

 

[Eeyore]

@Hip There could be an autoimmune component - but each time there is a trigger, usually identifiable after the fact. The initial one was definitely an infection, and likely viral, based on blood work in the ER the night I got sick. Triggers can be non-infectious too.

I don't think it's that uncommon in ME patients. Many people go through good and bad periods.

Obviously there are fluctuations from day to day, but everyone has fluctuations. In us they are just larger and more relevant because we are working off an impaired baseline.

 

[Eeyore]

@Sidereal The kind Dr. Hyde sees on SPECT scans. I'm sure it's more complicated than that but I don't know the details.