Do MEs cause CFS?

[rosie26]

I'll never forget the sore throat I had a day before my severe onset, it was the hottest, sorest throat I ever had in my life.

 

[Jonathan Edwards]

I think it may be more difficult to separate subgroups by history of symptoms than one might think. In rheumatology we see diseases with completely different mechanisms that can be indistinguishable on symptoms, maybe because symptoms are large a manifestation of the way the immune system responds, rather than what it is responding to.

 

[MeSci]

And do these ME1 patients suffer from the chronic sore throat of ME/CFS? My own chronic sore throat was caused by the virus that appeared to trigger my ME/CFS; the sore throat was the very first symptom this virus produced when I first caught it (and at the time of course I thought that it was nothing more than just a sore throat that would soon go away). However, my initial sore throat remained, and is still present to a degree even a decade later.

So I wonder whether the chronic or recurring sore throat often found in ME/CFS might be peculiar to the infectious onset-type ME/CFS, and thus be usable as a differential diagnosis between ME1 and the other MEs you enumerate which have infectious associations.

Just thought this poll on sore throat might be of interest. It's still open.

My own sore throat only appears to occur (intermittently) as a result of stale - possibly infected - secretions draining from my ear(s) or nose.

 

[ukxmrv]

My initial sore throat was accompanied by pus covered tonsils and very swollen glands (plus other symptoms). This has continued off and on for 30 years now.

The sinus infections came later on.

This could possibly be another subgroup. Patients with an unknown viral onset that keeps going.

 

[Hip]

With my virus, which Dr Chia diagnosed symptomatically as an enterovirus, when I first caught it, it produced a herpangina-type sort throat. Herpangina is a specific type of sore throat infection which involves inflamed red tissues on one or both sides of the arch at the back of the soft palette, either side of the uvula. Herpangina is usually caused by enteroviruses. The interesting thing is that the areas that were red and inflamed during my herpangina still look mildly inflamed today, a decade later.

Indeed, in ME/CFS you can find what has been termed crimson crescents on one or both sides of the arch at the back of the soft palette. Crimson crescents are just areas of purple-red inflamed tissue on this arch. There is a thread where patients posted pictures of their crimson crescents; the picture of my crimson crescent is here. Some have suggested that the presence of crimson crescents might be used as a rough diagnostic tool for ME/CFS.

I had some communication with Dr Chia about these crimson crescents, and suggested that the crimson crescent tissues might still host the virus from the original sore throat that led to ME/CFS. I thought the chronically inflamed-looking crimson crescent tissues might be an easier area to access for biopsies, compared to taking stomach tissue biopsies, which is Chia's gold standard way of detecting enterovirus in his ME/CFS patients. Dr Chia said (in an email):

"We have not looked crimson cresent since biopsy of this area usually need more anesthesia and is quite painful. One patient who had 5 biopsies of the throat because of persistent sore throat tested positive for enterovirus protein in the posterior tongue tonsils but negative in all the other ares of the throat including the red areas. This may be good to do but probably more invasive than a stomach biopsy, which does not usually cause much pain afterwards."

I wonder though if he had tested the red throat areas for enterovirus RNA (in order to detect the non-cytolytic, defective enteroviruses) rather than enterovirus VP1 protein, would he have obtained a positive result. In adult coxsackievirus B myocarditis, you find enterovirus RNA in heart muscle tissues, but you only very rarely isolate the live virus from these tissues.† This indicates the heart muscle hosts only a non-cytolytic, defective enterovirus infection. So like with the heart muscle tissues, perhaps in the crimson crescents contain only non-cytolytic, defective enteroviruses.

 

[Unduki]

I don't know anything about ME but I have this infectious disease doctor who has been researching CFS since the 70's with a group out of the University of Southern California. He sees patients from all over the US. I don't know how I ended up in his office but he told me CFS is caused by a virus and that Fibromyalgia is the body's response to trauma (emotional or physical.) He said I had CFS and that caused the Fibro. He prescribed 1 gram Valtrex, AKA Valaciclovir, 3 times every day. A normal dose for someone with Herpes Simplex II is one or two per day during an episode. Scary stuff but I was in a desperate, I'll try anything mood and darned if it didn't make a difference. I consider myself in remission after 2 years of anti-viral therapy. I don't think it's completely gone, I feel a "shadow" hanging there, so I don't let my guard down for one second. I stopped taking Valtrex after 2 years and consider myself very lucky to have had no side effects.

You have all these classifications for ME, very similar to the classifications for herpes. Are they the same thing? Dr. K says CFS is in the herpes family. He suggested it was herpes 6, AKA Stealth Virus.

 

[MeSci]

You have all these classifications for ME, very similar to the classifications for herpes. Are they the same thing? Dr. K says CFS is in the herpes family. He suggested it was herpes 6, AKA Stealth Virus.

There are lots of threads, including Phoenix Rising articles, about herpes viruses, including HHV-6, in relation to ME. You may find them interesting if you do some searches.

 

[Sasha]

I think it may be more difficult to separate subgroups by history of symptoms than one might think. In rheumatology we see diseases with completely different mechanisms that can be indistinguishable on symptoms, maybe because symptoms are large a manifestation of the way the immune system responds, rather than what it is responding to.

I mentioned on another thread that when I get a cold now, it has two peaks - I feel at my worst a few days in, then things improve, and then they get just as bad again, and then the cold fades out. I don't recall that pattern when I was healthy and I'm not sure if other PWME have it. If so, I wonder if that tells us anything about how the immune system is now functioning in at least one subset of PWME.

Of course, many PWME don't experience cold symptoms at all, even though they must be catching colds (I didn't either, for about seven years).

Do these reactions to new infection give us any useful information?

 

[MeSci]

Of course, many PWME don't experience cold symptoms at all, even though they must be catching colds (I didn't either, for about seven years).

Why must we be catching colds?

 

[Sasha]

Why must we be catching colds?

Good question - I was having second thoughts about that statement even as I was typing it! But I was thinking that we must surely be exposed to lots of cold viruses. It's been suggested that those PWME without cold symptoms have immune systems ramped up that jump all over the new virus and don't let it multiply. I've got no biomedical knowledge and have no clue whether that makes sense as an explanation.

I'm aware of course that many PWME are isolated (as I was during my first illness) so will have less exposure but it's unlikely to be zero exposure - even bedbound PWME will encounter carers or delivery people.

 

[MeSci]

Good question - I was having second thoughts about that statement even as I was typing it! But I was thinking that we must surely be exposed to lots of cold viruses. It's been suggested that those PWME without cold symptoms have immune systems ramped up that jump all over the new virus and don't let it multiply. I've got no biomedical knowledge and have no clue whether that makes sense as an explanation.

I'm aware of course that many PWME are isolated (as I was during my first illness) so will have less exposure but it's unlikely to be zero exposure - even bedbound PWME will encounter carers or delivery people.

Exposure to a pathogen doesn't necessarily mean that you will catch an infection. I'm not sure exactly what the definition is of catching an infection - perhaps @Jonathan Edwards can give us a concise one. I would guess that it means something like the pathogen getting past our first line of defence - the innate immune system?

 

[Jonathan Edwards]

My suspicion is that what Sasha is observing is not particular to PWME. I have the same sense that viral infections are now different from twenty years ago and often have two peaks. I think it is very easy for diseases to get into medical folklore and stay there long after they have disappeared. Doctors still record small lymph nodes on physical examination as 'shotty' apparently completely unaware that this term refers to the lead-shot like nodes left in the necks of people who had scrofula (head and neck TB) as children. Nodes of that sort had disappeared even before I became a doctor forty years ago.

Similarly, we still talk of 'colds'. Rhinoviruses may still cause seasonal epidemics as they did in 1960 but I have a suspicion that most of the viral infections we get now are not rhinoviruses but some thing else. Noroviruses have become very popular (or maybe unpopular). I think I may have mentioned my theory that rhinoviruses were epidemic in the early twentieth century because of universal state education, buses and handkerchiefs - which spread the viruses around the buses and at school. So the viruses that did best were the ones that made you blow your nose. I have not had a 'cold' like that for a decade at least. Now I get a sore throat and feeling lousy and it often comes and goes twice or even three times.

Unfortunately there is now virtually no research into viral epidemics as a routine in public health labs. So there is probably no clear documentation, other than perhaps the noroviruses that are a serious problem for people wit weak immune responses from cancer or transplantation.

 

[Sasha]

That's very interesting, @Jonathan Edwards! Though disappointing that our responses to new viruses don't give us a clue to what's happening in ME.

Coughing and sneezing viruses seem to be very popular still!

I hadn't thought about why rhinoviruses have that name but of course it means 'nose virus'.

 

[Snow Leopard]

Now I get a sore throat and feeling lousy and it often comes and goes twice or even three times.

I'm wondering why such viruses seem to come and go twice or three times?

I had one of those viruses this year, crazy runny nose, cough etc and I seemed to have the same virus coming and going three times (with maybe 3-4 weeks between each 'infection).

 

[A.B.]

I remember having one proper infection with fever in the last 15 years (since my gradual onset CFS started). I had a few very mild infections too, but so mild they were barely noticeable. Overall I seem less affected by infections than other people.

Immune system in overdrive?

 

[Jonathan Edwards]

I'm wondering why such viruses seem to come and go twice or three times?

I had one of those viruses this year, crazy runny nose, cough etc and I seemed to have the same virus coming and going three times (with maybe 3-4 weeks between each 'infection).

Cyclical fevers are of course well known with bacteria, perhaps because they enter the bloodstream in waves. This is not so usual with viruses although there may be cycles of viraemia for some. Maybe it is something to do with feedback cycle times in the immune response itself. Maybe the first bout of symptoms comes when the innate response is triggered by a first viraemic phase. Maybe a later bout occurs when antibodies are beginning to have effect on further periods of viraemia. I don't have any information on what is known about this. One other thing that might be relevant is that none of us seems to produce a solid long term immunity to noroviruses. Unlike other viruses you can get reinfection with them just as bad as the first time. That is partly why they are such a problem for people who are sick for other reasons.

 

[Hip]

none of us seems to produce a solid long term immunity to noroviruses. Unlike other viruses you can get reinfection with them just as bad as the first time.

That's intriguing; I was not aware of that. I assumed that all pathogens once encountered were remembered by the adaptive immune system.

 

[Snow Leopard]

Hi, @Jonathan Edwards, you may have answered this elsewhere, but I still don't understand how something like antibodies directed towards a particular cellular receptor would not lead to additional signs, specifically inflammation of a particular type of tissue, along with elevated IL-6/CRP/ESR?

Unless the receptors are expressed only in certain environments - but those environments are generally places where the antibodies won't get to either.

Which leaves mainly antibodies to extracellular signalling proteins as potential targets in ME/CFS?

 

[Jonathan Edwards]

Hi, @Jonathan Edwards, you may have answered this elsewhere, but I still don't understand how something like antibodies directed towards a particular cellular receptor would not lead to additional signs, specifically inflammation of a particular type of tissue, along with elevated IL-6/CRP/ESR?

Unless the receptors are expressed only in certain environments - but those environments are generally places where the antibodies won't get to either.

Which leaves mainly antibodies to extracellular signalling proteins as potential targets in ME/CFS?

There is a common assumption that binding of an antibody automatically leads to inflammation but this is far from the case. Inflammation is a process of calling cells out of the circulation into the tissue. So if an antibody binds to a receptor on a cell IN the circulation this cannot produce inflammation because the resulting signals would 'call cells in the circulation into the circulation' i.e. do nothing.

Also, to get inflammation from antibody binding you need either for the antibody to crosslink at least two Fc receptor by its back end (so you need at least two antibodies next to each other) or engage complement. A single antibody molecule cannot engage complement and it cannot cross link Fc receptors. So if an antibody binds to a receptor and blocks it or activates it there is no reason to get any inflammation. Inflammation only occurs if rafts of antibodies attached to some polyvalent structure cross link FcR or engage complement. So in thyroid disease an antibody can stimulate thyroxine production by binding to a hormone receptor with no trace of inflammation. In myasthenia gravis there is some complement activation at the endplate target but macrophages with Fc receptors cannot get in. Complement activation generates chemotaxins but not cytokines and IL-6.

So the idea that antibody binding = inflammation is just far too simplistic. One of the reasons why it took so long to understand the role of B cells in RA was that rheumatologists and immunologists didn't bother to think very hard. maybe the only people who did were Keith Peters and Georg Schifferli, but Peters got into medical admin and Schifferli into other lab things. The key point turned out to be that small complexes are dangerous when they FAIL to engage complement and as a result can access FcRIII in unusual places.

 

[Snow Leopard]

Also, to get inflammation from antibody binding you need either for the antibody to crosslink at least two Fc receptor by its back end (so you need at least two antibodies next to each other) or engage complement. A single antibody molecule cannot engage complement and it cannot cross link Fc receptors. So if an antibody binds to a receptor and blocks it or activates it there is no reason to get any inflammation. Inflammation only occurs if rafts of antibodies attached to some polyvalent structure cross link FcR or engage complement. So in thyroid disease an antibody can stimulate thyroxine production by binding to a hormone receptor with no trace of inflammation. In myasthenia gravis there is some complement activation at the endplate target but macrophages with Fc receptors cannot get in. Complement activation generates chemotaxins but not cytokines and IL-6.

Thanks for your reply. I'm wondering about what would be necessary to prevent complement binding, apart from basic steric restraints? (For IgM/IgG)