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A Little Poisoning Along the Road to ME/CFS
Looking at my symptoms, many of which are far less these days and some are gone, it would be easy to figure that I'd just been dealing with some heavy-duty menopausal issues.
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Do MEs cause CFS?

Discussion in 'General ME/CFS Discussion' started by Jonathan Edwards, Aug 10, 2014.

  1. Jonathan Edwards

    Jonathan Edwards Board Member

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    Continued from the thread: Who tried immunosuppressive treatment/drugs.

    Do MEs cause CFS?

    I thought I would set up this thread to discuss two thoughts about what ‘ME’ might be. One is that there are several MEs and the other is that MEs are maybe causes, not effects – which I will deal with first.

    There is debate about whether ME and CFS are much the same. Many researchers talk of ME/CFS as if they are. Others, like Kermit, may insist that ME and CFS, or at least ‘chronic fatigue’ must not be confused. Something that interested me when teaching students about diseases is that the medical profession often make no clear distinction between causes and effects. One might say ‘this lung damage is due to TB’ and one might also say ‘mycobateria can cause TB of the lung’. Or ‘osteoarthritis causes knee pain’ and football injuries cause osteoarthritis’. There is often some sense lurking in here but often there is also muddling. Which bit of the process is actually ‘the disease’?

    So my thought is that CFS is an effect – a pattern of symptoms and signs that we find people troubled by. But MEs, especially if we use the plural, are a quite different idea. They are perhaps ‘whatever the processes are that cause the CFS symptom complex in the absence of some other well recognised process’.

    In this form it seems to me that one cannot deny the existence of MEs, nor can one say that CFS will do instead. Even if one thought (as I do not) that all MEs are ‘bad thinking loops’ based on some entirely internal error in the way the brain sends itself (physical) signals we would have to admit MEs existed. And we would want to find out how they worked. (I think James Baraniuk’s approach is interesting. He has found two different patterns of ‘bad loops’ on fMRI scans.) There is no argument for saying that there is just an effect called CFS with no unknown causes.

    How many MEs would there be then? I doubt there is ever a precise answer to that sort of question. I am going to suggest that I suspect the existence of at least six. I base this partly on people I have had as patients and partly on what I have come to hear since last year. These groups are purely hunches, so I am not going to be able to give justify all the details. The emphasis is on immune regulation errors, because that is what makes sense to me, but everyone can probably think up some other sorts of MEs based on their own experience.

    1. ME1 is due to antibodies to certain nuclear proteins that can enter cells and disturb function on a body-wide basis. ANA is positive and usually speckled in pattern. (The proteins are likely to come under what are called ENA antigens, which are not always strictly nuclear but no matter.) The fatigue of ME1 is basically the same as in primary Sjögren’s syndrome and other ANA-linked illnesses that have names. I have met many people in this group. Some might suggest that they are well enough described to take them out of the ‘unknown causes’ that are MEs but a lot of these people end up labelled as ‘CFS with an ANA’. The fatigue may be a bit different from other groups.

    2. ME2 is due to an oversensitive resetting of cells that recognise what are known as Class I proteins, as in HLA-A, B and C. This includes T cells and NK cells. It probably follows a wide range of intracellular infections. As for ME1 it is in a sense a ‘covert’ form of a recognised illness, in this case Reiter’s disease. It may be more common in men and is likely to occur with sudden onset in early adult life. There may be local joint pains and a rise in CRP level but this may subside leaving persistent fatigue. ME2 and ME1 have nothing in common other than the end result.

    3. ME3 is not really a subgroup, but a causal component. It may ‘gang up’ with other MEs so that they feed off each other through regulatory pathways. ME3 is a resetting of brain sensitivity to all sorts of ‘noxious’ stimuli. It may well operate through feedback involving the autonomic nervous system. In some cases it may be reduced by the sort of voluntary strategies encouraged by ‘talking therapies’ but very often I suspect it is completely impervious. My own analogy is my tinnitus. Sometimes it seems unbearable and stops me sleeping or enjoying the quiet countryside and at other times I forget I ever had it. When it is there I cannot tell myself to not have it.

    4. ME4 is associated with anti-thyroid antibodies. It overlaps with the fatigue that occurs in people with overt autoimmune thyroid disease, which often does not change much when thyroid levels are re-balanced because it is not actually due to the abnormal thyroxine level. There must be complications here, because overt thyroid disease is rarely like severe ME. There may be overlap with e.g. ME1 or ME3 or there may be another unknown ‘partner process’. Anti-thyroid antibodies crop up in people with RA for no reason we can understand and RA itself seems to involve two processes that can feed off each other – one for anti-CCP antibodies and one for rheumatoid factor.

    5. ME5 is a speculation rather than something I have evidence for, but the specific autoimmune types I have given so far will not cover the majority. There is at least one more type needed and this is my guess. ME5 involves a sensitisation of the immune signalling mechanisms triggered by viruses. As part of an immune response to a virus the system produces antibodies that sensitise the ‘virus alarm system’ to the extent that even when there is no virus around it may trigger, just with exercise or stress. Two molecules might be particularly important here: gamma interferon and the immunoglobulin receptor FcRI (CD64) which is used to ‘pre-arm’ phagocytes with antibody even before any foreign pathogens have arrived.

    6. ME6 is probably a diverse group of MEs due to mitochondrial impairment. There may be an autoimmune process here too but in other cases there may be a major genetic component. So maybe it should be divided up further!

    Looking back over these my guess is that they might cover 50% of cases with luck, so it cannot be just 6. But at least it seems to me to make a nonsense of a ‘biopsychosocial model for CFS’. All MEs are bio, some may be biopsycho, maybe even some biopsychosocial (maybe the doctor is the 'social' cause here), but you don’t try to put 6 diseases into one model. You try to get to grips with each one on its own terms.
     
    Last edited by a moderator: Aug 10, 2014
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  2. lansbergen

    lansbergen Senior Member

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    Right, mine is not covered. Does not matter, I know what to do and you might get to it in due time.
     
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  3. deleder2k

    deleder2k Senior Member

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    @Jonathan Edwards

    Which of the different "MEs" would benefit from Rituximab? From what we have seen, it looks like 67% that satisfies the Canada criterias have a significant effect. Could some versions of ME be cured with Rituximab, while others need an infusion every now and then when B-cells are in the making?
     
    Last edited: Aug 10, 2014
  4. deleder2k

    deleder2k Senior Member

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    @Jonathan Edwards That was very interesting. Do you believe that there are many that do suffer from a form of ME which won't fulfill the Canada criteria? Do they suffer from M.E, or could it be lyme, or simply psychosomatic? Some claim to have M.E and believe they are cured by Lightning Process.
     
  5. alex3619

    alex3619 Senior Member

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    ME5 seems to be a variant of the emerging microglial view. There is now growing evidence for this.

    I have long said, based on how the breakdown of various studies occur, that ME is either likely to be at least two types, or one disease with two manifestations. This is because many studies seem to show two subgroups, with about a 30-40/70-60 split. Of course two may be just disease symptom clusters, and underlying causes could be mutltifactorial with different subgroups as suggested, or even other subgroups. Its hard to quantify or specify the unknown.

    However thinking along these lines can lead to defined research questions, and hence studies to see if they are right.

    Then there is always the issue of rare genetic disorders. Most are probably not discovered yet. These are probably small percentages of patients, disorder by disorder, but collectively it could be a high percentage.
     
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  6. ukxmrv

    ukxmrv Senior Member

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    Where would you place the ME outbreaks like the Royal Free one?
     
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  7. greeneagledown

    greeneagledown

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    @Jonathan Edwards

    You proposed an ME subtype (your ME4) that is associated with anti-thyroid antibodies. Is the UK rituximab team considering doing anti-thyroid antibody testing on the subjects in the clinical trial to see if patients who are positive for anti-thyroid antibodies tend to respond better than other patients? Seems like an easy way to both identify a subgroup and also identify an effective treatment for that subgroup. If not, do you know if this is something the Norway team is thinking about?

    I have ME/CFS as well as anti-thyroid antibodies even though my other thyroid tests are normal, so I'm very interested in this theory. I didn't know that this was a somewhat common finding in ME/CFS.
     
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  8. Mij

    Mij Senior Member

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    @greeneagledown can I ask how long you've been ill? Did you have a thryoid scan?

    The reason I'm asking is that I had "extremely elevated" anti-thyroid anti-bodies at the onset of my illness. They have since gone down on their own.
     
  9. greeneagledown

    greeneagledown

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    Hi, @Mij. I've had ME/CFS for 6 years following a case of mono. Unfortunately, I only recently had anti-TPO testing done for the first time, so I have no idea how my numbers have fluctuated during my illness.
     
    Last edited: Aug 10, 2014
  10. Jonathan Edwards

    Jonathan Edwards Board Member

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    Well of course this is where multifactorial causation has to be opened up - mix and match your trigger and your response maybe. But I think this would most likely go under ME5 for me. Reiter originally described an epidemic but people had rashes and swollen joints. I think if it was ME2 there would be some clues like that. Presumably some particular virus strain was particularly good at triggering an aberrant response. And if you have a large enough number of people like hospital staff it may be that the 'epidemic' gets notice in a way that it would not if a virus was working its way through the general population gradually. Of course the Royal Free had another problem with Legionnaire's disease in the water system so maybe it wasn' a virus!
     
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  11. Jonathan Edwards

    Jonathan Edwards Board Member

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    I think it would be sensible to look at that but I suspect it would not be used as the primary end point for statistical power. We have the problem that there are so many things one could look at and if we look at lots then apparent correlations will pop up by chance. The numbers with any particular antibody will be small and I do not know whether the Norwegians had anybody with thyroid antibodies in the first trial.
     
  12. Jonathan Edwards

    Jonathan Edwards Board Member

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    I think we start getting in to trouble with definitions here. There probably are people with severe fatigue who do not fit Canadian criteria and deserve just as much thought but I never had a specific ME practice so I don;t know from personal clinical experience. In the UK I would be surprised if Lyme disease accounted for many cases. I am not sure that I find 'psychosomatic' a convincing label. Does it mean people think themselves into having symptoms or believe they have symptoms they don't really have? The former can certainly flavour and aggravate all sorts of illnesses. I have just had a strange mole taken out and the doctors letter said it could be melanoma - until the path came back OK. I had plenty of symptoms I could have done without out after the letter came. But I knew perfectly well that they could be just worry and I find it very hard to believe this is a big issue for severe CFS. And I really don't know if you can believe you have a symptom you do not have. Minds do strange things but it seems a contradiction.
     
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  13. chipmunk1

    chipmunk1 Senior Member

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    where are the people that have psychosomatic CHES - chronic high energy syndrome. people complaining of having too much energy because they falsely believe that they have too much energy.
     
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  14. daisybell

    daisybell Senior Member

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    Hi @Jonathan Edwards

    I am very interested to read your thoughts, and wonder if you could expand further on how these sub-types fit with the profile of an apparent trigger e.g. Parvovirus, with auto-immune markers gradually appearing? Are these events actually unrelated, but due to the timeline and symptoms, causally linked in our minds or can one ME sub-type cause the emergence of others down the track? Do you think someone can fit under more than one label?

    I would say that I started with ME5 but now have type 1 and possibly 4... ( of course I may be wrong!)
     
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  15. deleder2k

    deleder2k Senior Member

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    I agree the word psychosomatic is not very convincing, but what about all the people that reportedly went from being completely bedridden to running marathons again. Could it be that some of them had some form of ME (1-6), recovered after some period of time, but that they didn't know they were healthy again? It sounds very strange. LP is very big in Norway and the U.K for some reason. On the other hand; in a lot of countries like Sweden, the rate of CFS seem relatively low. I guess you can blame GPs knowledge about CFS/ME for that. I don't know about the U.K, but in Norway, the CFS/ME debate is still being characterised by the "psychosomatic" view or the belief that ME is a stress disorder.

    Gosh, I look forward to the day Fluge and Mella publishes phase 3 of their study.
     
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  16. Valentijn

    Valentijn Activity Level: 3

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    The Dutch biopsychosocial (BPS) group does something similar, in dividing ME/CFS into two distinct disease processes, while still claiming they are the same psychosomatic disorder.

    Because some patients push themselves too hard and constantly crash as a result, they don't fit the usual stereotype of ME/CFS patients having a presumed exercise phobia. Hence this BPS group suggests that one group of patients has kinesiophobia (an absurdity in itself compared to real phobias), and the rest have unrealistic expectations of their own capabilities as they age, etc, and exceed their normal limitations.

    So somehow they conclude that people with completely different causative psychological and behavioral issues, resulting in either inactivity or overactivity, are suffering from the same illness. And these vastly different psychological and behavioral disorders then produce identical symptoms :p
     
    Last edited: Aug 10, 2014
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  17. Jonathan Edwards

    Jonathan Edwards Board Member

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    The questions are beginning to get too tricky! The trouble is I think it can work both ways around. The virus may trigger a hyper-responsiveness or the hyper-responsiveness may be there waiting for the first virus to show it up. I am sceptical about some of the standard stories about infectious triggers like molecular mimicry but I have to admit that for ME viral episodes somewhere at the beginning do look as if they must be relevant to at least some subgroups.

    I strongly suspect that many of my subgroups can 'gang up' and overlap and maybe slip from one to another but I would also hold out for the idea that some are just completely unrelated - like ME1 and ME2. We see that in autoimmune rheumatic diseases. Some can overlap and some have nothing to do with each other even though they can be almost impossible to tell apart.
     
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  18. DanielBR

    DanielBR Senior Member

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    Very interesting discussion. To the lightning process. I don't believe it actually works in ME (or in any other disease). It seems to be a very misguided version of cognitive psychotherapy. I can imagine, for some mild or moderate cases it functions as a coping strategy and helps them to ignore symptoms or to have a more positive outlook. The Process suffers from the same dangerous loop than any other psychosomatic therapy. If it works, the doctor get all the credit, if it doesn't the patient is to blame for not trying hard enough. Why it helped some severe patients is a mystery to me.

    @Jonathan Edwards

    If I understand you correctly, you think ME1 is an autoimmune disorder like Lupus and Sjögrens, in which ENAs are attacked. Do you think an unknown ENA is involved or do you think it is more of an overlap with known diseases. As far as I am aware, patients with other ANA diseases are not exercise intolerant. Or are they?

    In ME5, do you think the B-Cells are sensitised and constantly arm the immune system to kill the long gone (or latent) viruses? And this is why Rituximab could break the cycle of an over stimulus?

    Have you any idea, why so many of us suffer from severe OI and POTS like symptoms? The regulation of the vascular tone seems to be severely impaired. In which category would you put these symptoms?
     
  19. Jonathan Edwards

    Jonathan Edwards Board Member

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    Yes, but then there are enough peculiar people about to provide stories for newspapers, particularly if the reporters have to use an old story because news is slack or someone is putting on a show for other reasons! A fat cheque from a journalist or even from some healing agency that happens to be run by ... And there are also a small number of sad people with pathological attention seeking behaviour. These situations often show themselves for what they are, but I am not sure I have ever seen 'psychosomatic illness' show itself for what it is because it is unclear what that would be (at least to me).

    But I guess that we could explain the dramatic recoveries with a scenario that ME2 led to ME3. The ME2 faded out, as it may very often do, but the ME3 got embedded in the brain circuitry. Except that with enough endorphine or something maybe the brain can flip out of ME3 if it is not underpinned by something else.

    Strange things do happen even with autoimmunity. I had one patient who I looked after with rheumatoid arthritis for fifteen years and then all of a sudden she developed hypothyroidism. We treated that without trouble and her RA vanished as well, only to be replaced by a completely new illness, temporal arteritis. And occasionally RA just disappears for no apparent reason at all.

    I don't pretend to be able to explain all the possibilities - but then that is sort of the message here - to keep thinking each case is different.
     
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  20. Ninan

    Ninan Senior Member

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    According to most Swedish physicians, ME/CFS doesn't exist. It's not even a potentially debilitating psychosomatic illness, it's non existent. And hence the patient trying to lie down in the chair in front of them is not sick. That's probably the reason why there seem to be quite few PWME:s in Sweden. They're at home trying to cure a weird kind of depression that doesn't make them sad but is giving them a high fever every time they exercise.

    It's so obvious in some cases that it's hard to ignore. I got sick the same week I had an ear infection. I was completely healthy the week before (I think?) and have never been well since. The week after I had my first outbreak of EBV. It might be difficult to separate the hen from the egg here, ME could have made me more prone to infections the same day it started. Even though I've hardly ever had an infection since. But I don't think so, I'm pretty sure the infection was the trigger. Together with lousy genes and a stressful period in my life. That "three strike theory" Horning talks about fits my experience perfectly.
     
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