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Surprisingly good outcomes for people who get ME/CFS after Mononucleosis (Glandular Fever)

Simon submitted a new blog post:

Surprisingly good outcomes for people who get ME/CFS after Mononucleosis (Glandular Fever)

Sometimes ME/CFS emerges after mononucleosis, or glandular fever. Simon McGrath shares results from a long-term follow-up study from Haukeland University Hospital in Norway...
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"When will this end?" It's a question that most ME/CFS patients have probably asked themselves and their doctor many times. I certainly have.

Yet there is astonishingly little hard data on recovery rates from this illness or on how much patients improve, and the evidence there is doesn't give too much hope.

Step forward a long-term follow-up study that shows unexpectedly good rates of improvement for younger people who developed ME/CFS after infectious mononucleosis (glandular fever) – though the results are hardly spectacular.

Around 11 years on from getting sick, just over half of all ME/CFS patients were able to work part or full-time, though fatigue levels remained high:

The study was led by Dr. Morten Nyland and comes from the Neurology department of Haukeland University Hospital in Norway, site of the famed Rituximab pilot study. In fact two of the authors of this new paper were part of that pilot study. And although this wasn't a trial, patients were encouraged to use self-management (pacing/activity management), and the authors concluded that this probably contributed to the relatively good outcomes.

How the study worked (important)

An ideal study would take a bunch of patients and follow them at consistent time points, say the start of the illness, and then five and 10 years later. In this case, though, researchers made the most of pre-existing data to access a large group of patients who were followed up at very different times in their illness, an approach using two contact points that still yields invaluable results.

"Contact 1" was the first time the patient was seen by the specialist ME/CFS clinic at Haukeland University Hospital, any time between 1996 and 2006.

"Contact 2" was a follow-up questionnaire sent to all patiets in 2009, an average of 6.5 years later. There was huge variation in follow-up time between patients, for example at the second and final contact in 2009 one patient had been ill for 24 years and another only five years. The study had data at both contact points for 92 patients, making this one of the largest follow-up studies going.

At the initial contact, patients had been ill for an average of nearly five years, and again that hides a lot of variation. Half had been ill for 3.2 years or less, a quarter for under two years. The higher average was because some had been ill for a very long time. The patients were also relatively young (the average age was 24 years), reflecting the age profile of infectious mononucleosis, the 'kissing disease', which particularly affects young adults and teens.

Over half of all patients were employed at final contact

Pleasingly, the study used employment status as the clear-cut, objective primary outcome -- and arguably the ability to earn a living is the outcome that matters most to patients. The graph below shows a lot of improvement between first and second contact, which an average gap of six years, though the gap will vary a lot between patients.

Unemployment is in red while employment (full-time or part-time) or being a student is in green. Onset is when they got ill, Contact 1 is typically five years later, and Contact 2 typically another six years on.

Clearly things have improved for many patients, but the overall situation at Contact 2 remains a great deal worse than onset.
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Note that half of those employed at Contact 2 were working full-time, compared with only 1 in 10 at Contact 1, so presumably there has been an increase in hours worked per person, as well as more people working.

Caution: It's possible that 11 years from onset (age 35 vs. age 24 at onset) some people would not be working anyway due to raising families so unemployment might not be zero even for a healthy group. And employment at onset wasn't split into full-time/part-time.

How patients said their overall health had changed

The study also asked patients how their overall health had changed since Contact 1 (their first visit to the clinic). Most patients said they had improved, 12% reported they had got worse.



Fatigue was also rated at both Contact 1 and Contact 2 using the Fatigue Severity Scale which gives an average score ranging from 1.0 (no fatigue) to 7.0 (maximum fatigue); any score of 5.0 or higher counts as severe fatigue. The average score at Contact 1 was 6.4, falling to 5.0 at Contact 2 -- so even after this improvement the group as a whole was right on the threshold of severe fatigue.

Different degrees of improvement

The study measured 'improvement' in several different ways. As well as change in employment status, they looked at self-rated improvement (including an option of 'recovered') and change in fatigue scores.

You can see that 'improvement' ranged from 70% reporting any improvement, to 32% moving into employment, and 13% who rated themselves as recovered.


Most people improved, even those who hadn't improved at Contact 1.

Another encouraging point was that of the 26 people who said they had already improved at Contact 1, 25 improved again by Contact 2. And of the 38 who reported they hadn't improved before, 25 (66%) improved by Contact 2.

Fatigue improved much less than employment status


One slightly strange finding, which the authors didn't comment on, is that average fatigue levels fall rather modestly compared with the percentage improving in employment status. While 32% of patients were able to start working, fatigue scores only fell from 6.4 to 5.0.

It seems likely that this in part is down to people getting back to work but still struggling, so that their level of fatigue doesn't improve as much as it might.

Interestingly, although 28% were working full-time only 13% rated themselves as 'recovered', which supports the view that some people are improving and choosing to work full-time despite not being completely well, and may still be struggling quite a lot.

What 'predicts' return to work/improvement over time? (not a lot)

Overall, this important new study shows that outcomes for younger people who develop ME/CFS after mono are not great, but are probably better than expected. Around half were in work 11 years after onset, though fatigue remains high for most.

What might be driving this improvement? The authors ran some fancy analysis to see what features (such as symptoms and age) predicted being in employment or an improved fatigue score at the final contact. It turned out that only lower joint pain at Contact 1 was associated with later employment, but the effect was small.

Similarly, low joint pain and depression at Contact 1, and better eduction, were predictors of less fatigue at Contact 2 -- but again the effect was small.

Surprisingly, length of illness was not an important predictor of employment or fatigue. Generally those with shorter illnesses are seen as having a better chance of recovery, but that doesn't appear to have been the case here.

It's possible that outcomes for ME/CFS after mono are better than after other triggers. I'll give the last word to the authors themselves, who suggest that both pacing/activity management and financial support through sickness benefits were likely to have played an important role to improvements:

"Self-management strategies, long-term sickness absence benefits providing a stable financial support, in addition to occupational interventions aimed at return to work were likely contributors to the generally positive, prolonged outcome."
Simon McGrath tweets on ME/CFS research

Phoenix Rising thread discussing this paper, including the more detailed post that led to this blog.



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Continue reading the Original Blog Post
 
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Confirmed mono at age 35 preceded my symptoms worsening from a fibromyalgia definition to an ME definition. Reading this article was interesting, but it seemed somewhat misleading. Of course, working as opposed to being housebound or confined to bed is a much, much better "outcome" for anyone, but this disregards quality of life long-term. Were these people completely self-sufficient? How would they rate their own quality of life? I am not expecting answers to those questions from this study, of course, but it brings up factors to be used for the future.
Hi Gracie
I'm glad you are able to work a bit now, and hope it continues and your health improves. The article tried not to be misleading:
Around 11 years on from getting sick, just over half of all ME/CFS patients were able to work part or full-time, though fatigue levels remained high:
Your experience fits with this speculation:
Interestingly, although 28% were working full-time only 13% rated themselves as 'recovered', which supports the view that some people are improving and choosing to work full-time despite not being completely well, and may still be struggling quite a lot.
And of course we don't know whether or not these people will continue to be able to work

Perhaps I shouldn't have used 'surprisingly good', though that was in the context of typical outcomes for people with this illness.
 
@Simon I do agree with that! I do appreciate efforts to study this. What a puzzle it has been. Maybe with the progression in identifying subgroups, others will be spared this plight. I do see the hope. I just cannot appreciate the labels without the rest of the story.

There is a human tendency, I think, to say, Well, there you go. You are okay. (Not you personally.)

I made it to this point once before, but knew I was headed for trouble. The signs were there. Not sure it would last, I applied to occupational rehab, which I was told to do by Workforce Services. Long story short, I think they had a good laugh at me processing the request, the rejection letter was so full of mockery and sarcasm. It was pretty bad, to the verge of funny had it been a funny topic,

Inside two years, my job was gone. My car died. My rental lease was determined invalid, and I was evicted suddenly. I was flat broke and abruptly homeless, just like that, with nearly no resources to remedy my plight. It was scary, unnecessary, painful - and yet I was still considered a-bod by government services, though I was back to walking dead. With no money to see the doctor who would not consider helping establish the disability paper trail, life was dark for a while.

That is where I am coming from as I read.

Without help, that hole would have been impossible to crawl out of. It wasn't coming from any government program designed to be the safety net. I went straight through the cracks.

Between church, local community, and one sympathetic sibling, I was able to obtain a room rental and get through for several months. About the time my motivation to be on my feet was being scrutinized and questioned, both my parents passed away inside five days. It's not how anyone would choose resources, but suddenly I had money to take a year and rest, try new remedies, regroup, etc. I was expected to retrain as well, though in time that proved impossible.

It was a sticky situation for years on end, one all too familiar in this crowd. Somehow or other we have to survive while these things are hashed out.
 
I made it to this point once before, but knew I was headed for trouble. The signs were there. Not sure it would last, I applied to occupational rehab, which I was told to do by Workforce Services. Long story short, I think they had a good laugh at me processing the request, the rejection letter was so full of mockery and sarcasm. It was pretty bad, to the verge of funny had it been a funny topic,

Inside two years, my job was gone. My car died. My rental lease was determined invalid, and I was evicted suddenly. I was flat broke and abruptly homeless, just like that, with nearly no resources to remedy my plight. It was scary, unnecessary, painful - and yet I was still considered a-bod by government services, though I was back to walking dead. With no money to see the doctor who would not consider helping establish the disability paper trail, life was dark for a while.

That is where I am coming from as I read.

Without help, that hole would have been impossible to crawl out of. It wasn't coming from any government program designed to be the safety net. I went straight through the cracks.

Between church, local community, and one sympathetic sibling, I was able to obtain a room rental and get through for several months. About the time my motivation to be on my feet was being scrutinized and questioned, both my parents passed away inside five days. It's not how anyone would choose resources, but suddenly I had money to take a year and rest, try new remedies, regroup, etc. I was expected to retrain as well, though in time that proved impossible.

It was a sticky situation for years on end, one all too familiar in this crowd. Somehow or other we have to survive while these things are hashed out.
Dreadful. You need a lot of inner strength to get through all that crap. I have usually fallen through cracks in safety nets too.
 
Great article @Simon, thanks very much for writing it.

There seems to be one or two resisting the idea that ME/CFS patients can recover, perhaps because the possibility of recovery somehow negates the seriousness of this disease, perhaps making ME/CFS look, in the eyes of the public and doctors alike, like a more trivial disease. Whereas this might be the case, nevertheless, it means the resistance is for political reasons, not scientific ones. Scientifically, this looks like a good study.



Anyway, I'd like to make some points:

(1) The study found that after around a decade, 28% of these mononucleosis-triggered ME/CFS patients were back in full time employment (but no doubt struggling with it), and 13% said they were recovered. Consequently, when there are articles about ME/CFS recovery stories in the press, these should not be automatically met with contempt and incredulity (as they often are on ME/CFS forums), because this new study does clearly show that recovery can and does occur.

Indeed, it says here that in England and Wales, a conservative estimate puts the number of mononucleosis-triggered cases of ME/CFS at 3113 per year. That means, just from mononucleosis-triggered ME/CFS patients alone, we should expect to see 13% x 3113 = 405 ME/CFS full recovery cases each year in England and Wales. And that figure does not include any full recovery cases from other causes of ME/CFS.


(2) Consider that the patients found on ME/CFS forums might not be that representative of ME/CFS patients as a whole. The reason why people are here is because they have ME/CFS. You probably won't find many former ME/CFS patients here, because I imagine most of those will be getting on with their lives, and will have put ME/CFS behind them. Thus this may bias the cross-section of ME/CFS patients found on these forums. So people on the forums may get the impression that recovery is rare, but that might be due to this possible bias of the type of patients on the forums.


(3) The overall significance of this study for ME/CFS patients in general depends on what percentage of ME/CFS patients have this mononucleosis etiology. So for example, if only 1% of ME/CFS patients had this mononucleosis trigger, then the results of this study would have little bearing and relevance for ME/CFS in general. But if say 30% had this mononucleosis trigger, then the results would be much more relevant.

How can we estimate the percentage of ME/CFS patients who had a mononucleosis trigger? Well this study found that the incidence of CFS was 9% after mononucleosis (glandular fever), and the authors gave a conservative estimate is that mononucleosis accounts for 3,113 new cases of ME/CFS per annum in England and Wales.

But what is the incidence of ME/CFS overall? Well, this study (see fig 3) says that in 2001 in the UK, for every 100,000 persons, each year 50 will develop ME/CFS. Now the total population of England and Wales is 56 million, so from this we can calculate that the total incidence of ME/CF is 28,000 new cases per year in England and Wales.

Thus now we can see that:

11% of ME/CFS patients have a mononucleosis-trigger etiology.

(calculated from 100 x 3,113 / 28,000 = 11%).

So this gives 11% figure gives us some sense of how significant this new study on recovery rate is for the ME/CFS community: we now can see that around 1 in 10 ME/CFS patients will have a mononucleosis trigger, and as mentioned, of these, 28% will be back to full time work after around a decade, and 13% will be recovered.


I would like to see a study on the recovery rates of enterovirus-triggered ME/CFS; I have a hunch this may harder to recover from. As we now know, in chronic enterovirus infections, the virus is capable of creating an unusual type of intracellular infection (called a non-cytolytic enterovirus infection), which may be much harder for the immune system to eradicate or control.



(4) As for what virus caused these cases of mononucleosis and the ME/CFS that ensued: it says here that Epstein-Barr virus causes mononucleosis in more than 90% of cases, and it says here that cytomegalovirus causes 7% of cases. So EBV and CMV account for nearly all mononucleosis cases.

However, that does not necessarily imply that the 90% EBV and 7% CMV figures also apply to these mononucleosis-triggered ME/CFS patients. It might conceivably be the case, for example, that CMV mononucleosis is behind most mononucleosis-triggered ME/CFS.
 
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@Hip i wonder if there is some other underlying infection that suppresses the immune system that makes it easier for one to get mono or maybe mono that is harder to recover from?

I keep thinking that these ebv/cmv reactivations generally only occur in immune suppressed. So is there some other infection such as lyme, which Dr Lerner finds dont respond to avs until bacterial infection is treated. Or do we have some immune defect that does allow us to suppress ebv/cmv??

I would like to see a group of chronic mono patients treated so there nk function is returned to normal and see if treating this immune dysfunction treats the cause?? My thoughts and what i have researched, are that these herpes infections avoid the immune system by somehow lowering our own interferon, which is what helps drive our nk function???

As a side note, interferon is well known to treat enteroviruses, so could EV or EBV be the immune suppressant????
Or one effects the other?
 
@heapsreal
Those speculations are certainly all interesting ones, but I guess they could equally apply to other chronic viral diseases.

Why, for example, do some people who catch a coxsackievirus B infection go on to develop chronic CVB myocarditis from it (which is a chronic coxsackievirus B infection of the heart muscle that can cause heart attacks and can lead to dilated cardiomyopathy); but others who catch the same virus don't get this chronic illness?

I saw direct evidence of this: the ME/CFS-triggering virus I caught, which was diagnosed by Dr Chia as an enterovirus, also infected several friends and family, and out of these, two people immediately developed viral myocarditis with heart attacks, and one other infectee developed this illness some years later. I had the exactly same virus, but I developed ME/CFS rather than myocarditis. But why might that be? Why was I protected from myocarditis, but succumbed to ME/CFS?

I also wonder why chronic CVB myocarditis is not prevalent in ME/CFS, given that is it caused by the same Coxsackie B virus that is strongly linked to ME/CFS, and found in the bodies of many ME/CFS patients. You'd think therefore that ME/CFS patients might be prime targets for chronic CVB myocarditis, but this heart disease is not a common comorbidity of ME/CFS. That is strange, isn't it? So why is that, I wonder?

It might be that whatever factors predispose patients to developing ME/CFS from a coxsackievirus B infection somehow also protect these patients from developing chronic CVB myocarditis.



Another example of different responses to viral infections is the fact that 90% of all poliovirus infections are completely asymptomatic, a small percentage of infections lead to some minor symptoms, and about 0.5% of infections lead to full poliomyelitis (and some will die from it). So this virus goes from producing no symptoms at all, to causing fatal illness, depending on the person.
 
@heapsreal
Those speculations are certainly all interesting ones, but I guess they could equally apply to other chronic viral diseases.

Why, for example, do some people who catch a coxsackievirus B infection go on to develop chronic CVB myocarditis from it (which is a chronic coxsackievirus B infection of the heart muscle that can cause heart attacks and can lead to dilated cardiomyopathy); but others who catch the same virus don't get this chronic illness?

I saw direct evidence of this: the ME/CFS-triggering virus I caught, which was diagnosed by Dr Chia as an enterovirus, also infected several friends and family, and out of these, two people immediately developed viral myocarditis with heart attacks, and one other infectee developed this illness some years later. I had the exactly same virus, but I developed ME/CFS rather than myocarditis. But why might that be? Why was I protected from myocarditis, but succumbed to ME/CFS?

I also wonder why chronic CVB myocarditis is not prevalent in ME/CFS, given that is it caused by the same Coxsackie B virus that is strongly linked to ME/CFS, and found in the bodies of many ME/CFS patients. You'd think therefore that ME/CFS patients might be prime targets for chronic CVB myocarditis, but this heart disease is not a common comorbidity of ME/CFS. That is strange, isn't it? So why is that, I wonder?

It might be that whatever factors predispose patients to developing ME/CFS from a coxsackievirus B infection somehow also protect these patients from developing chronic CVB myocarditis.



Another example of different responses to viral infections is the fact that 90% of all poliovirus infections are completely asymptomatic, a small percentage of infections lead to some minor symptoms, and about 0.5% of infections lead to full poliomyelitis (and some will die from it). So this virus goes from producing no symptoms at all, to causing fatal illness, depending on the person.


I guess this all shows, in general, how poor testing is for chronic active infections. Next would be actually treating them.

As for what you said about myocarditis from EV, i guess it depends on where the infection goes?
I think with ME its a low grade brain infection, encephalitis/meningitis type of condition.

Something i would like to know more about is chickenpox and EV, as dr chia has mentioned it being the great imitator. Chickenpox was one the infections that started my ME and i always wonder if it was EV as i had chickenpox when i was a child also?
 
There seems to be one or two resisting the idea that ME/CFS patients can recover, perhaps because the possibility of recovery somehow negates the seriousness of this disease, perhaps making ME/CFS look, in the eyes of the public and doctors alike, like a more trivial disease. Whereas this might be the case, nevertheless, it means the resistance is for political reasons, not scientific ones.

Whilst you make a number of interesting observations in the rest of your post, @Hip, I have to respond to this.

I suspect that many - perhaps most - of us are actually here to find out how to attain recovery, or at least expedite the development of effective treatments that will bring this about. We long to hear about credible treatments.

What people object to are the suggestions that our illness can be treated through psychology or exercise.

I'm sure many of us are well aware that the seriousness of an illness does not correlate directly with its curability. Many serious illnesses are often cured, such as some cancers, pneumonia, meningitis and thrombosis.
 
Also bear in mind, @Hip, that IIRC 'recovery' was not objectively measured in this study but self-reported. This message cites a small study in which self-reported recovery did not correlate with normal health.

It's not that people don't want to recover; it's that we want the full facts, warts and all.
 
What people object to are the suggestions that our illness can be treated through psychology or exercise.

Well, yoga is a bit more than just exercise, it is a method of cultivating the mind through the body, yet in this recent thread, there were quite a few strong objections to the plausibility of a news story about one ME/CFS patient who felt they had recovered through yoga and dietary changes.

As this Google search indicates, yoga can modulate the autonomic nervous system and vagus nerve, so given the autonomic dysfunction in ME/CFS, and given theories like Michael VanElzakker's which postulate that a vagus nerve infection causes ME/CFS, it becomes less surprising perhaps that yoga may, in some subset of patients, have benefits.



Prior to developing ME/CFS, I did quite a bit of yoga (in the days when yoga didn't have the more "commercial" and somewhat secular packaging it often has now), and I can vouch for the fact that yoga can have profound spiritual and calming effects on the mind. That was the main reason I did it.

When my ME/CFS was at its worst, though, I was far too weak physically to do more than one or two yoga asanas (yoga poses), so I can certainly appreciate that yoga will be impossible for many ME/CFS patients. However, that does not rule out the possibility that some patients may be able to do some yoga, and that out of those who can, some small subset, or even just a handful of patients, might benefit from yoga.

Reading that press article about a possible ME/CFS recovery from yoga has made curious about trying it, because due I think to various medications I take, my ME/CFS has improved quite a bit over the last few years, especially in terms of my physical stamina (but my mental stamina is still very poor), so now I would be capable of doing some yoga.



I should add that for me personally, I am looking at this from a scientific point of view, ie, I want to know the medical truth of the matter, rather than a political point of view.

The political view is different: it revolves around the dishonest and manipulated GET/CBT studies which purport show some patients can recover for ME/CFS using these therapies, when in fact the authors of these studies have done things like dishonestly redefined the meaning of the word recovered in the "small print" of the study, so that they can falsely claim that exercise therapy leads to recovery.

Politically, ME/CFS patients tend to be vehemently against the notion that a physical exercise might be beneficial for ME/CFS, and I total concur with this vehemence. In fact I spent a lot of time writing comments (like this one) on the articles about GET/CBT, where I did my best to expose the lies behind the GET/CBT studies. So I do my bit in the political battle against the GET/CBT nonsense.

However, there is also the maxim that "truth is the first casualty of war," which means that anything which looks remotely like physical exercise may get shot down by ME/CFS patients in the flak of battle.

I tend to be more interested in the truth rather than political spin. Spin is what the Wessely school depend on, because there is little truth behind GET/CBT.
 
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@Hip, I have not dismissed the possibility of yoga bringing benefits, but a cure seems implausible.

I am, however, completely open to the possibility of a cure through diet, and have blogged on the subject as well as posting info in my profile. Diet is a physical treatment and has huge effects on the gut microbiome.

Some people are sceptical of this too, but that doesn't mean that they believe ME is incurable.
 
I would have been the exception if the study expanded to year 14 for me. Mild relapse at year 8 (misdiagnosed as depression), moderate at year 14 (cut work back to 32 hours) . Had substantial debilitating relapse year 15 1/2 (had to quit work) then in year 20 developed into progressive decline until present, 95% bedbound similar to when I originally got sick at age 15. Year 24, I found follicular b cell non-hodgkins lymphoma in nasolabial area (aka lower tear duct gland) and throat lymph nodes ( many anecdotal reports of cancers in these areas for % of ME patients). Rituximab temporarily got rid of cancer, ME symptoms worsened due to chronic multiple viral infections acquired during Rituximab treatment.
 
@Gingergrrl, what I meant was this: what if your prognosis depends not on your age, but on the nature of the event that triggered your onset?

Now, we know that post-EBV ME is more common in younger than older people. This is because most people - with some exceptions like yourself - have encountered EBV by the time they get to their mid 30s, so ME occurring after this age is only rarely going to involve EBV/mono as the triggering event.

If post-EBV ME has a better prognosis than other types of onset, then that younger group - which contains more EBV-onset cases - might show better recovery for that reason. Not because they're younger as such, but because more have EBV as their onset.

I don't know if that's the case at all. But its a possibility. It does seem to me that there are mutliple ME's. Acute onset ones do seem to have a better prognosis than gradual, and I think this is probably because they reflect different disease processes.

Is positive EBV antibodies common?
 
So, I am sort of kidding here, but maybe not really?.......in the fact that I think my only hope of improvement may be to kiss someone with mononucleosis so I can get it. I am a cfs/m.e. sufferer looking for answers on a slow decline since 1991. Now bedbound much of time. Tried all treatments western and eastern medicine offered. Had hopes to try Rituxa_____( spell) chemotherapy one day but saw some bad result outcomes in some on it. So this article looks like mononuclosis may be the better route. I ve been on all the antivirals and most recently Valcyte 900 mg qd. No improvement. Mononucleosis may make my body kick into proper immune gear? I must say i truly doubt this would be the good outcome but willing to try anything after all these years of living dead with m.e.