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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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Yeah, although it is wise to be very cautious about any definition of recovery, when you look at the earlier ME outbreaks, IIRC a sizable proportion improved or even recovered within months of onset (the definitions of recovery may have not been particularly rigorous or comprehensive though). It's the ones who failed to improve or recover early on which had the most problems later on. Some of the remaining patients improved very slowly over time but many remained severely ill for decades or relapsed frequently. However, I think Jason et al (?) published a very long term followup which found that even those who reported a recovery were still significantly worse off on most measures compared to healthy controls.

My symptoms started as an adolescent around the same time a sibling began a struggle with suspected glandular fever. Even though I had chronic problems with sore glands and blocked sinuses (on top of a bunch of other symptoms I tried to keep to myself), at the time I didn't really put it together, and the first doctor I reached out to suggested that I probably have "growing pains", then after a naturopath failed to help I was left to think it was psychological, although I always struggled with that conclusion because its explanatory power seemed inadequate compared to symptoms.

It was distressing but impairments were relatively mild in the early years, but I was open to mind over body ideology, pushing through symptoms, and (multiple failed attempts at) regular exercise. It was trying to live an ordinary life and being subjected to quackery which triggered long term descents into the pit. If I knew back then a fraction of what I knew now and got a proper diagnosis with proper advice, I don't think I would be nearly as chronically affected as I am now decades later. On the other hand part of me always felt down deep that whatever mistakes I made only accelerated the enviable.
 
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However, I think Jason et al (?) published a very long term followup which found that even those who reported a recovery were still significantly worse off on most measures compared to healthy controls.

This study?

J Clin Psychol. Author manuscript; available in PMC Mar 3, 2014.

Published in final edited form as:
J Clin Psychol. Sep 2012; 68(9): 1028–1035.
Published online Jun 29, 2012. doi: 10.1002/jclp.21880
PMCID: PMC3940158
NIHMSID: NIHMS551018
Understanding Long-Term Outcomes of Chronic Fatigue Syndrome
Molly M. Brown, M.A.,1 David S. Bell, M.D.,2 Leonard A. Jason, Ph.D.,1Constance Christos,1 and David E. Bell, MPH2
Author information ► Copyright and License information ►

The publisher's final edited version of this article is available at J Clin Psychol
See other articles in PMC that cite the published article.

Go to:
Abstract
Objective
This study sought to examine long-term health, symptom, and disability outcomes among patients with chronic fatigue syndrome (CFS) by comparing those diagnosed with CFS 25 years ago with healthy controls.

Method
Of the 25 participants diagnosed with CFS 25 years ago, five self-reported that they maintained a diagnosis of CFS, while 20 reported no longer having a diagnosis. These two groups were compared with healthy controls on outcomes related to functioning and symptom severity.

Results
Those who remitted from CFS showed significantly more impairment on 21 out of 23 outcomes compared to controls. On 17 outcomes, those who remitted had non-significant differences in impairment compared to those who maintained a CFS diagnosis.

Conclusions
Findings from this study suggest that over time many individuals will not maintain a CFS diagnosis but will not return to their premorbid level of functioning.

I think I remember David Bell talking about these kids and remarking that once they lost OI they considered themselves recovered but in actuality they were still sick compared to normal controls, they had just used various strategies to adapt their lifestyles to ongoing symptoms.

My symptoms started as an adolescent around the same time a sibling began a struggle with suspected glandular fever. Even though I had chronic problems with sore glands and blocked sinuses (on top of a bunch of other symptoms I tried to keep to myself), at the time I didn't really put it together, and the first doctor I reached out to suggested that I probably have "growing pains", then after a naturopath failed to help I was left to think it was psychological, although I always struggled with that conclusion because its explanatory power seemed inadequate compared to symptoms.

It was distressing but impairments were relatively mild in the early years, but I was open to mind over body ideology, pushing through symptoms, and (multiple failed attempts at) regular exercise. It was trying to live an ordinary life and being subjected to quackery which triggered long term descents into the pit. If I knew back then a fraction of what I knew now and got a proper diagnosis with proper advice, I don't think I would be nearly as chronically affected as I am now decades later. On the other hand part of me always felt down deep that whatever mistakes I made only accelerated the enviable.

My history is very similar. I never fully drank the psychology koolaid but when I was younger I struggled with many ever-changing symptoms which I kept to myself for as long as I could. I almost never went to the doctor as I was always somewhat doubtful about their organic basis and never did anything to really educate myself properly about the management of this disease because I preferred to pretend that ME/CFS doesn't exist, or if it does, that I didn't have it. I was doing all the wrong things for many years as a result of my ignorance.

Doing exactly what psychology thinks we should all do, i.e. trying to live a normal life and ignoring/pushing through symptoms is what ultimately led to complete disability. I became bedridden after I stupidly went against my innate skepticism and gut feeling and gave in to the GP's badgering to embark on a diet & gentle informal graded exercise programme of daily walks. Doing that diligently for about 12 months is turned my previously mild ME (working full time with difficulty) into severe and almost completely bedridden.

As for mononucleosis, I've never had it but when I was a child my brother who was a teenager at the time had a severe version lasting for months and his body temperature forever remained a degree lower than normal although he has so far not developed other ME/CFS symptoms. My own health problems soon followed including the low body temp which developed some years later.
 
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I would like to know out of the people who recovered what they did to help their recovery if anything- did they change diet for instance ?as maybe there is a link to why some people get well and others don't ?
 
I'm not quite understanding this sentence and keep re-reading it. Do you mean if you are younger, your infection is more acute (meaning severe) or something else? If it is more acute or severe, why would that have a better prognosis? Mine was extremely acute and severe.

In medical terminology, acute means of short and sharp course, often severe (but I don't think it has to be severe). It's in contrast to chronic, which is long-term.
 
I wonder if this study continues following these people if the researchers will see something similar?
This is an interesting thought, @Lynn. Your profile sounds very much like mine: onset at 25 with mono-like illness (not confirmed through blood tests at the time), followed by long mono-like episodes (low grade fever, etc.), but able to return to work at 29. I'm now 50 and having my worst crash in 22 years.

Obviously, that sort of thing isn't going to show up in the time frame studied here.
 
I know lots of stuff suggests the younger you are, the better your prognosis, and that could well be true. But there's another possiblility: it could be if you're younger, the onset of your CFS is more likely to be acute EBV. And it could be that EBV-onset has a slightly better prognosis.

I'm not quite understanding this sentence and keep re-reading it. Do you mean if you are younger, your infection is more acute (meaning severe) or something else? If it is more acute or severe, why would that have a better prognosis? Mine was extremely acute and severe.
@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.
 
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.

@Woolie I guess what I am still trying to clarify (using the theory of the article- which I still have not read!) is, would my case be considered acute? I became very ill immediately after a minor surgery and five days later diagnosed with mono from EBV. I was extremely ill, the sickest of my entire life, from the mono for about 6-8 weeks. But then I fully recovered (or so I thought) until I got another infection about 10 months later which led to tachycardia, dysautonomia, and a gradual decline from Jan 2013 to the present but with the last six months being an extreme worsening of my symptoms. So is this acute or chronic?
 
@Woolie I guess what I am still trying to clarify (using the theory of the article- which I still have not read!) is, would my case be considered acute? I

I don't think this is all that uncommon in "acute onset" cases. There's an acute viral illness that appears to resolve, then later down the line, the person gets what seems to be a relapse. And so on. Maybe others could comment, but I still think this fits the sudden onset profile better than the gradual onset.

If you can identify a clear turning point in your life when you went from being completely normal to quite messed up, then its sudden onset, even if there are some relapses and remissions along the way.
 
Simon, there is nothing pleasing about being in part time work in your 30s, as these people seem to be. In your 30s you need to be in full time work to be on a path that will enable you to support yourself and have a retirement. In this case only 27% have full time jobs, which is proper employment. "Part-time" could be five or ten hours a week. Also, being fatigued all the time, even if you are in the lucky 45% with full time work, does not allow for a full life. In fact 100% of these people are not leading the life they could if decent medical research were done and treatment available.
Home-makers should be taken account of. Those with children and no child-care help should be scored as in full-time work.
 
I would like to know out of the people who recovered what they did to help their recovery if anything- did they change diet for instance ?as maybe there is a link to why some people get well and others don't ?
I would like to know too! But this was not part of the study, I'm afraid.

Simon, there is nothing pleasing about being in part time work in your 30s, as these people seem to be.
I completely agree - the 'pleasing' part was that they used an objective measure (employment) rather than a less-reliable self-report scale as the primary measure:
Pleasingly, the study used employment status as the clear-cut, objective primary outcome


Also, being fatigued all the time, even if you are in the lucky 45% with full time work, does not allow for a full life.
Again, I agree. I think the results are better than I've seen for other studies (which is what I meant by 'surprisingly good') but still not impressive. I'd tried to reflect this in the blog:
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:
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*.
* this edit was made early on for the blog but didn't get picked up by the system to change the version on this thread - apologies, this has now been done.


Home-makers should be taken account of. Those with children and no child-care help should be scored as in full-time work.
That's a very good point. I did mention that even a healthy population probably wouldn't be working full-time at this age because of childcare, but the study would have been stronger if the researcher had measured home-making in an equivalent way to employment,
 
It seems odd to me that the authors would go to all the trouble of tracking these patients over a number of years, and yet not try to establish that it was EBV that caused their mono-like symptoms. Perhaps this was because it was (partly) retrospective, and they didn't have access to the patient's initial test results. I agree that most doctors should be trying to confirm EBV in cases of mono, at least in a country like Norway, but in a scientific paper you would hope that there would be some evidence of this. I couldn't even find the part that someone else quoted about it being based on physicians reports, in fact it seemed rather to be based on a retrospective questionnaire, which is hardly enough to define the cohort as 'ME mono.'

Re: the twin peaks, I think both suppositions (i.e. that is it two diseases, or that it is the same disease) are plausible. But there is a third supposition too: that there are more than two diseases here. These could either contribute to the peak pattern (i.e. the first peak could represent the increased incidence of two (or more) diseases at that age) or they could just contribute to the overall incidence without significantly affecting the peak pattern (this is more likely to happen if there are many diseases).
 
It seems odd to me that the authors would go to all the trouble of tracking these patients over a number of years, and yet not try to establish that it was EBV that caused their mono-like symptoms. Perhaps this was because it was (partly) retrospective, and they didn't have access to the patient's initial test results. I agree that most doctors should be trying to confirm EBV in cases of mono, at least in a country like Norway, but in a scientific paper you would hope that there would be some evidence of this. I couldn't even find the part that someone else quoted about it being based on physicians reports, in fact it seemed rather to be based on a retrospective questionnaire, which is hardly enough to define the cohort as 'ME mono.'
Yes, it was because they saw all these patients after they developed cfs and after the initial mono - hence they recorded 'mono' not EBV as the cause. Which seems fair enough - they only claimed what they knew.
The paper methods section said:
The 111 patients constitute all patients diagnosed with CSF triggered by mononucleosis in the total cohort of 873 patients. The diagnosis of mononucleosis was based on the physician report following the patient to our clinic.
 
Thanks for finding the quote, but again it's not very reassuring - perhaps we can ask Lansbergen, but what does "the diagnosis of mononucleosis was based on the physician report following the patient to the clinic" mean? It could mean what you assumed it meant, but it could also mean that it was based on the physician's report, following the patient being referred to the clinic. Plus, the diagnosis of mono is hazy one, since there are many mono-like illnesses out there.

I think we will have to wait for the Jason study into EBV mono in university students to conclude before we can say that what proportion of people with EBV Mono might end up being diagnosed with ME.
 
In the species I observed there is only one known herpes virus. That was not found in the population I was watching but it became a problem in some other populations.

Thanks for finding the quote, but again it's not very reassuring - perhaps we can ask Lansbergen, but what does "the diagnosis of mononucleosis was based on the physician report following the patient to the clinic" mean? It could mean what you assumed it meant, but it could also mean that it was based on the physician's report, following the patient being referred to the clinic. Plus, the diagnosis of mono is hazy one, since there are many mono-like illnesses out there.

I think we will have to wait for the Jason study into EBV mono in university students to conclude before we can say that what proportion of people with EBV Mono might end up being diagnosed with ME.
 
Sorry, I'm not quite sure what you mean, but I mentioned you because I thought there might be a Norwegian version of the paper that might be a little clearer about how the patients were diagnosed with mono.
 
Simon, there is nothing pleasing about being in part time work in your 30s, as these people seem to be. In your 30s you need to be in full time work to be on a path that will enable you to support yourself and have a retirement. In this case only 27% have full time jobs, which is proper employment. "Part-time" could be five or ten hours a week. Also, being fatigued all the time, even if you are in the lucky 45% with full time work, does not allow for a full life. In fact 100% of these people are not leading the life they could if decent medical research were done and treatment available. Home-makers should be taken account of. Those with children and no child-care help should be scored as in full-time work.

@deboruth I agree with you on everything you said (although certainly not Simon's fault and he is just the messenger reporting on the study!) But I agree that someone could still be extremely ill for decades but somehow be able to work 5-10 hours per week which would count as a "part-time" job. Plus others may be mild to moderately ill but killing themselves to continue working but have no other quality of life. At closer look, this study does not give me much hope.
 
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.

Currently, I am working part-time, and have been for nearly three years. My job is mostly physical, but with this illness, ANY job is physical. Sitting behind a desk is hard for me. My future is a question mark. My case looks good on paper - 75% function, back at work, mostly self-sufficient. But... my outcome is still being written. Can I make it to retirement age without a major crash and burn? Can I sustain this? Will I need more help? What happens to me with no retirement fund? Sure, I am ahead of the game earning a paycheck, but it does not take away other realities. I am still seen as short-sighted and irresponsible, for instance, that I do not have a retirement fund.

Quality of life? Fantastic compared to being confined to bed. Still poor, though, as I have to come straight home from work and do little more than rest flat on my back. If income is the measure, I am cutting it. But we need far more factors than that to call it a great outcome.

Long-term sustainability is my biggest goal in life right now!