Is CDC Out to Bury PEM?

[Bob]

Not sure people are getting it. If Fukuda (let alone e.g. NICE Guidelines) are capturing 80% + people with PEM why is there a need to change criteria? That is what must be argued and proved for CDC et al. to move on.

Ah, so that's where she mentions the 80% figure. Thanks Russ.

I've just re-watched the video and, as you say, Unger says that over 80% of patients who meet the Fukuda CFS definition either 'have' or 'endorse' post-exertional malaise.

...why is there a need to change criteria?

I agree that defining ME in terms of clinical settings is more complicated that many of us acknowledge.
But I think the reasons to separate patients with PEM from patients without PEM has been discussed in this thread.
Many people believe that ME patients, with PEM, have a distinct illness (or at least a group of very similar illnesses) that warrant being segregated for clinical treatment and research purposes. PEM is also one way to attempt to distinguish ME patients from idiopathic fatigue, so people advocate for separation for political and treatment reasons, attempting to separate ME from idiopathic fatigue or fatigue with a psychological basis.

I acknowledge that this is a very complex subject, and our community has clearly failed to successfully advocate that ME should be treated as an illness with a distinct set of symptoms, rather than as part of wide spectrum of fatiguing illnesses. Not because of a lack of effort though.

I remain unconvinced that PEM - physical - is unique to and defining of ME. And I am rather sick to death of hearing debate surrounding 'Pure ME' or even 'Genuine ME'.

I find that language unhelpful as well, for various reasons, one of which is that it means different things to different people.

(Jane Colby believes that ME is caused by an enterovirus in the gut, and anything else isn't ME. Some people only subscribe to the Ramsay definition of ME, which most patients haven't even heard of, and some subscribe only to the ICC which is a brand new criteria.)

 

[Snowdrop]

@taniaaust1, all very good points, that I find hard to disagree with. But our message is falling on deaf ears and perhaps government decision-makers might be more receptive to our advocacy if we were to use language that they can easily relate to.

I reckon that Unger is not receptive to the CCC because it doesn't allow her to serve 'ME/CFS' patients without PEM. Unger will always have to consider what happens to CFS patients without PEM. I think we might be able to encourage her to move in the right direction by using language that she is amenable to. Unfortunately this is playing politics, but sometimes politics is a fact of life even in health care.

We've been asking for a distinct illness called 'ME' to be recognised for 30 years or so and it's had no more effect than collectively banging our heads on a wall, for 30 years. Most health care providers look at us as if we are deluded if we talk about ME being distinct from CFS. And most health agencies and government don't have any insight into the difference between chronic fatigue and ME. So our advocacy hasn't exactly been successful. Do we continue for another 30 years with the same strategy, advocating for something that no one understands and that no health agencies can buy into? Or do we start to talk in terms that they can understand and that they can work towards incrementally?



I support the use of the CCC but it diagnoses ME/CFS, and not ME.
So where does that leave us in terms of separating ME from CFS, and not accepting a 'CFS' label?
It seems like a mixed message.



So do I, but it's been happening for 30 years and our advocacy has had zero effect because they still use Fukuda, and P2P has even dropped the question asking them to investigate the differences between ME and CFS.


That would be nice. CFSAC recently discussed their recommendation of rolling out a national program of clinical centres of excellence, and they commented on how their recommendation has been persistently ignored.

I agree that's it's possible to over reach and thereby come away with nothing (if that's what the stakes are: all or nothing).
That's not to say that we don't deserve to get all of the change necessary to help get those in authority to a place where real progress is made.

It occurred to me to think of this in terms of tectonic shifts. Before the big 'earth changing' earthquake there are smaller rumblings and adjustments to the geography, the the big shift (in paradigm). But the little shifts have to happen.

 

[Keela Too]

IMO - Doctors should have a broader definition of ME (or CFS or whatever their country calls it) than researchers.

Why?

Well I would rather a few extra depressed/fatigued individuals were given advice to pull back from exercise, than one extra ME sufferer was told to go and do Graded Exercise for recovery.

This is the precautionary principle. Do no harm. The net for capturing all ME patients will never be perfect - better it is slightly wider than slightly too narrow. At least in the doctors' surgeries.

Research is different.

Researchers need clean cohorts. And one of those cohorts should be a group who demonstrate PEM.

 

[Bob]

IMO - Doctors should have a broader definition of ME (or CFS or whatever their country calls it) than researchers.

Why?

Well I would rather a few extra depressed/fatigued individuals were given advice to pull back from exercise, than one extra ME sufferer was told to go and do Graded Exercise for recovery.

This is the precautionary principle. Do no harm. The net for capturing all ME patients will never be perfect - better it is slightly wider than slightly too narrow. At least in the doctors' surgeries.

Research is different.

Researchers need clean cohorts. And one of those cohorts should be a group who demonstrate PEM.

Unfortunately all CFS/ME patients (with or without PEM) in the UK are prescribed graded exercise therapy, unless we decline it. It's the only 'treatment' on offer.

 

[jimells]

Can we start writing to every senator, send letters. What can we do???

Cause trouble, disrupt business as usual, raise the costs of the current policies. Anything less is just noise they can drown out with diversions such as the ridiculous and useless CFSAC meetings. Unfortunately this requires people capable of physical activity and travel. That mostly leaves us out.

My impression is that the AIDS activists were successful because queer folks had been forced to organize before the epidemic took hold. We're not organized. The people who should be our supporters are not organized, and seem to show little interest in really supporting us. This shows the effectiveness of the propaganda machine, that our families have chosen to believe official lies instead of the people experiencing the illness every day of their lives.

 

[Bob]

My impression is that the AIDS activists were successful because queer folks had been forced to organize before the epidemic took hold. We're not organized. The people who should be our supporters are not organized, and seem to show little interest in really supporting us. This shows the effectiveness of the propaganda machine, that our families have chosen to believe official lies instead of the people experiencing the illness every day of their lives.

Actually, I'm not sure if that explains the difference between ME advocacy and AIDS advocacy. There was propaganda surrounding HIV/AIDS in the early days, and plenty of it. And I think many of us have fully supportive families, although unfortunately some of us have families that struggle to understand the illness. I think the difference is that whole communities were being decimated by HIV/AIDS in the 80's, and lovers/partners/sons/brothers (it was mainly males being infected in the gay community) were becoming ill suddenly and dying soon afterwards. So there was a major shock factor involved, whereas our illness is a slow-burn. To put it bluntly, were not dying quickly enough for governments to sit up and take notice.

 

[Keela Too]

Unfortunately all CFS/ME patients (with or without PEM) in the UK are prescribed graded exercise therapy, unless we decline it. It's the only 'treatment' on offer.

I know... I'm one of them!! It's a situation that needs to change.

Here in N.Ireland we are hoping to have the CCC adopted and a petition has already been presented to our Local Assembly at Stormont...

We can but try.

 

[Mij]

Fatigue and pem can be accumulative and one can be in a constant state of pem too? ?

I think the constant pem is common in those that work especially when in bed when not at work and then notices improvement when they get 2 weeks off. Maybe it's the constant pem that causes many to crash ie straw that broke the camels back? ?

Interesting. The PEM I expience is what prevents me from going at a steady continuous pace and being able to work. I don't notice irmprovment after resting- I return to baseline after 24hrs of rest. I think we may be talking about the same thing but from different perspectives?

 

[jimells]

To put it bluntly, were not dying quickly enough for governments to sit up and take notice.

Yes, this makes a lot sense. Thank-you for pointing this out. I remember the truly outrageous hate spewed out by the mass media during those years. The "Christian" fundamentalist preachers were the worst, followed by medical people who refused to treat or even get near the patients. Gay men are still not allowed to donate blood in many places, a holdover policy from decades ago.

I can imagine there were many early AIDS patients who were also abandoned by friends and family. At the same time there were many advocates who put their careers and liberty on the line. Where are the advocates willing to do that today?

 

[Firestormm]

Unfortunately all CFS/ME patients (with or without PEM) in the UK are prescribed graded exercise therapy, unless we decline it. It's the only 'treatment' on offer.

If you are mild or moderate this is true. Personalised is the word used in NICE and I take that to mean what is says. A programme tailoured to the individual need. We can debate of course what people's own experience have/have not been with GET prescriptions: and these tend to naturally affect our feelings towards any offering.

Severe patients are steered towards 'graded activity' - as are indeed those moderate patients who are unable to maintain GET. I still think that the word 'graded' is used differently by different practitioners.

Grading means literally measuring the effect each activity/task (which might include exercise) you need/want to do will potentially have on you and then thinking how best to approach this as a task you want to attempt i.e. by breaking it down or seeking an alternative or by seeking help and assistance with it.

For others - notable in GET - grading appears to mean a therapy that increases the amount of exercise specifically you do regardless of the symptoms it might cause. You keep increasing and pushing through. But I personally have never encountered a practitioner who prescribes such a thing for ME or any other condition. Not one who will keep on pushing a patient who is clearly struggling.

Not that I am ever saying others have not been as fortunate as me of course.

 

[MeSci]

Yes, this makes a lot sense. Thank-you for pointing this out. I remember the truly outrageous hate spewed out by the mass media during those years. The "Christian" fundamentalist preachers were the worst, followed by medical people who refused to treat or even get near the patients. Gay men are still not allowed to donate blood in many places, a holdover policy from decades ago.

I can imagine there were many early AIDS patients who were also abandoned by friends and family. At the same time there were many advocates who put their careers and liberty on the line. Where are the advocates willing to do that today?

There are still nutters who blame gays for things like bad weather, e.g. a councillor from bunch-of-clowns party UKIP:

http://www.bbc.co.uk/news/uk-england-oxfordshire-25793358

Yes, there were early AIDS sufferers who were abandoned by friends and family. I knew one of the early victims in London, and it caused a huge and tragic rift amongst some of his friends because they - or one of them - considered that his partner had abandoned him. I never found out the whole story but it was all very sad. My own guess is that his partner (with whom I am still in occasional contact) was simply terrified out of his wits.

People didn't know then how it could (and couldn't) be passed on, so I don't think he could be blamed for such terror. I never tried to find out the full details as no one seemed to be forthcoming with them and I didn't want to risk being drawn into the feud. As it was, both sides seemed to think that I was on their now-enemy's side, when I wasn't taking either side.

It was a time of great fear and recrimination, which is what happens in the face of the unknown.

In Africa it is still common for sufferers to be ostracised.

Perhaps coincidentally, one of the people who specialised in studying and disseminating info about AIDS at the beginning was Anthony Pinching, who went on to work on ME.

 

[MeSci]

Maybe ME-with-PEM needs a completely new name. If PEM is what defines it, maybe it should be Exertional Injury Syndrome, Post-exertional Damage Syndrome (although 'PEDS' has perhaps unfortunate associations). Can't really call it Exertional Damage Syndrome as that would confuse it with Ehlers-Danlos Syndrome.

 

[Bob]

Below is an extract from an IACFS/ME conference abstract that Tania highlighted on another thread, that discusses misdiagnosis. (My emphasis in red text)...

CFS/ME and fatiguing illnesses: differential diagnoses from a community-based sample.
Nicoletta Carlo-Stella MD, PhD , free professional, Pavia, Italy
[...]
Materials and Methods: [...] 89 consecutive self-referred patients complaining of PENE (post-exertional neuroimmune exhaustion) (1) were seen in a private practice specializing in CFS/ME from 2007 to 2012. A thorough work-up including history, clinical examination, lab testing and imaging, when necessary were undertaken.
[...]
Results: [...] A diagnosis of CFS/ME was confirmed in 36 patients (40%); however rheumatological diseases (43%), endocrine disorders (5,6%), psychiatric diseases (5,6%), gastrointestinal diseases (4,5%), haematological cancer (2,2%) and urological bladder cancer (1,1%) accounted for the remaining 60 % of diagnoses of patients complaining of fatigue.

Tania highlights that all the misdiagnosed patients complained of experiencing "PENE" (see the red text above.)

This gives much food for thought "self-referred patients complaining of PENE (post-exertional neuroimmune exhaustion)" Why did it turn out that 60% of them had other illnesses and not ME/CFS seeing they had PENE or thought they did.

Can we not trust at all that PENE helps define this illness??? or is it the case of many who have ME/CFS not really understanding what PENE is and saying they have it when they do not at all? I want to know how PENE was defined to these people who said they had it.

I think this ties in with Beth Unger's claim that it is difficult to define/determine/identify post-exertional malaise, as it relates to ME/CFS, in general practitioner clinical settings.
Unless someone has actually experienced ME symptoms, and an ME crash, it is difficult to understand what PEM/PENE describes.
I think the same goes for general practitioners: Most general practitioners know almost zero about ME/CFS, so they're not likely to understand the exact nature of post-exertional malaise as it applies to ME.

The name "post-exertional malaise" is not particularly helpful at describing its nature (i.e. the name doesn't describe the experience of a post-exertional crash.)
Everyone (including healthy people) experiences post-exertional fatigue, so it's not surprising if many people, including other patient groups, also identify with the words 'post-exertional malaise'.

The abstract mentions that 43% were subsequently re-diagnosed with rheumatological diseases. I've heard before that people with arthritis have post-exertional flare-ups, and experience fatigue, so perhaps it isn't surprising that they identified with 'PENE' or 'PEM', and it would not be entirely surprising if they'd previously been misdiagnosed with ME/CFS by incompetent general practitioners.

I know someone who has a damaged back, and who suffers from pain and fatigue if they do too much activity. So that's another case where someone might identify with 'post-exertional malaise'.

Anyway, I'm just highlighting this to demonstrate the difficulties.
I don't think that general practitioners are capable of distinguishing PENE from normal post-exertional fatigue, or post-exertional symptoms in other patient groups.
So I think that Beth Unger has got a point.

I wonder if we can come up with any practical solutions in terms of identifying PENE in clinical settings? (I think we all agree that a two-day CPET test isn't practical for all ME patients in clinical settings.)
I think Lenny Jason may have the best potential solution, that I'm aware of, via the DePaul Symptom Questionnaire.

 

[Valentijn]

I think the answer is right here:

A thorough work-up including history, clinical examination, lab testing and imaging, when necessary were undertaken.

Does the CDC advocate a very thorough work-up as part of the CFS diagnostic process? Not really.

Patient-reported PEM is still an immensely better criterion than patient-reported fatigue.

 

[Bob]

I think the answer is right here:

A thorough work-up including history, clinical examination, lab testing and imaging, when necessary were undertaken.

Does the CDC advocate a very thorough work-up as part of the CFS diagnostic process? Not really.

That's where clinical centres of excellence would be useful.

Patient-reported PEM is still an immensely better criterion than patient-reported fatigue.

Do we have data on the sensitivity and specificity of self-reported PEM in terms of diagnosing ME?

 

[MeSci]

Below is an extract from an IACFS/ME conference abstract that Tania highlighted on another thread, that discusses misdiagnosis. (My emphasis in red text)...

Tania highlights that all the misdiagnosed patients complained of experiencing "PENE" (see the red text above.)



I think this ties in with Beth Unger's claim that it is difficult to define/determine/identify post-exertional malaise, as it relates to ME/CFS, in general practitioner clinical settings.
Unless someone has actually experienced ME symptoms, and an ME crash, it is difficult to understand what PEM/PENE describes.
I think the same goes for general practitioners: Most general practitioners know almost zero about ME/CFS, so they're not likely to understand the exact nature of post-exertional malaise as it applies to ME.

The name "post-exertional malaise" is not particularly helpful at describing its nature (i.e. the name doesn't describe the experience of a post-exertional crash.)
Everyone (including healthy people) experiences post-exertional fatigue, so it's not surprising if many people, including other patient groups, also identify with the words 'post-exertional malaise'.

The abstract mentions that 43% were subsequently re-diagnosed with rheumatological diseases. I've heard before that people with arthritis have post-exertional flare-ups, and experience fatigue, so perhaps it isn't surprising that they identified with 'PENE' or 'PEM', and it would not be entirely surprising if they'd previously been misdiagnosed with ME/CFS by incompetent general practitioners.

I know someone who has a damaged back, and who suffers from pain and fatigue if they do too much activity. So that's another case where someone might identify with 'post-exertional malaise'.

Anyway, I'm just highlighting this to demonstrate the difficulties.
I don't think that general practitioners are capable of distinguishing PENE from normal post-exertional fatigue, or post-exertional symptoms in other patient groups.
So I think that Beth Unger has got a point.

I wonder if we can come up with any practical solutions in terms of identifying PENE in clinical settings? (I think we all agree that a two-day CPET test isn't practical for all ME patients in clinical settings.)
I think Lenny Jason may have the best potential solution, that I'm aware of, via the DePaul Symptom Questionnaire.

I note that the first extract says

rheumatological diseases (43%), endocrine disorders (5,6%), psychiatric diseases (5,6%), gastrointestinal diseases (4,5%), haematological cancer (2,2%) and urological bladder cancer (1,1%) accounted for the remaining 60 % of diagnoses of patients complaining of fatigue.

(my bolding).

Is that just sloppy reporting?

Also, could they not have had ME AND the other illnesses?

Another thought - sorry if it has been answered before - but do we know, or at least have some idea of - biological correlates of PEM/PENE?

I've recently been looking at inflammatory cytokines and suspect that they are significantly involved. I have just added an edit at the end of my leaky gut blogpost referring to inflammatory cytokines, notably how they can arise from both exertion and leaky gut, and in another blogpost I look at how they may account for at least some PEM/PENE symptoms (through mineral and fluid loss).

There must be other conditions which involve leaky gut and/or inflammatory cytokine release following exertion.

 

[Nielk]

That's where clinical centres of excellence would be useful.


Do we have data on the sensitivity and specificity of self-reported PEM in terms of diagnosing ME?

@Bob -

I recently read a very good blog regarding PEM/PENE - http://www.cfsfacts.org/2012/09/pene-explanation-of-icc-term.html

"This section will propose an immuno-inflammatory explanation for the
hallmark symptoms of the disease,including fatigue, malaise,
neurocognitive symptoms and a range of abnormal responses to exertion
that may be delayed by 24 or even 48 h, which is often labeled as post
exertional malaise. The term refers to abnormal responses to even a
trivial increase in normal levels of physical or neurocognitive
activity.Post activity relapse may therefore be a better term. This
phenomenon is often reported by ME patients to be similar to the acute
phase of influenza, with symptoms indicating infection/inflammation,
e.g. sore throat, lymph tenderness or swelling, malaise, hyperalgesia
and brain fog. Insignificant increases in physical activity or minor
cognitive tasks may exacerbate immune dysfunction,inflammation and O&NS
thereby producing further signs of the disease. The effect may be
delayed, but is predictable and accumulative, varying in duration
dependant on disease severity and accumulative activity levels. "

(Morris and Maes, 2012)

It seems to me this symptom has be evaluated as a matter of intensity and severity.

If a healthy person, not accustomed to running, will attempt to run a mile, it is understood that fatigue will ensue.
When a person suffers from any other fatiguing illness, like autoimmune illnesses, they will tire more easily than a healthy person. For example. they will not have the stamina to go running. They might not be able to work overtime. They might have to rest more often than a healthy person.

The reaction of a person who has ME to increased activity whether physical or mental, is one of remarked intensity compared to other fatiguing illnesses.

When in my youth, I suffered from active Crohn's, I was easily fatigued. If I overdid things, I would take a rest and then be able to resume normal activity.

To compare that to how I react to increased activity with my ME is like comparing a match to an explosion.

Isn't most of medicine a matter of severity? A temperature of 100 would not be alarming but, 104 in an adult will raise concern.

In addition, as the blogger above highlighted, some of the distinct symptoms of PEM/PENE of sore throat etc. is as far as I know unique to ME.

In addition, since when do we have to conform our set of criteria based on what is easily understood by regular clinicians? Can they not understand our unique features of and intensity of our PEM/PENE?

 

[Bob]

It seems to me this symptom has be evaluated as a matter of intensity and severity.

I don't see how PEM can be defined by the severity of the reaction.
I can have a severe and long-lasting (i.e. months or years) PEM reaction or a mild and short-lasting (i.e. a few days) PEM reaction, depending on where my health is at, and what activities I've done to cause a flare-up.

In addition, as the blogger above highlighted, some of the distinct symptoms of PEM/PENE of sore throat etc. is as far as I know unique to ME.

Yes, I agree that PEM in ME has unique characteristics.

In addition, since when do we have to conform our set of criteria based on what is easily understood by regular clinicians?

Perhaps that's the link that I've been missing from this discussion.
Beth Unger wants to have a definition that is easily workable by a general practitioner.
But we need clinical centres of excellence where patients are diagnosed and treated by experts.
That would surely solve the problem that Beth Unger highlights.

 

[Anne]

Are we sure Fukuda is capturing people with PEM to 80%+? Isn't that figure from the multi-site study where there population consists of the patients of seven of the most experienced ME/CFS clinicians in the States (most of whom are likely to use narrow criteria)?

I also received an e-mail from Dr Unger, and I, too, was disappointed by her reply. She maintains the position that PEM should not be a mandatory symptom for ME/CFS, but she doesn't answer my questions about the logic behind this (Only symptoms that are easily measurable with current medical technology can be a mandatory part of a case definition?) and she doesn’t mention how this applies to the other typical symptoms of ME/CFS. Fatigue/fatiguability, muscle pain, joint pain, sore throat, headaches are surely all as hard to identify or quantify in a standardized way as PEM? If there are validated ways of self-reporting these symptoms, then it is of course possible to create a standardized way to report PEM as well.

To me, the thing is that our best ME/CFS clinicians and researchers are promoting a definition which includes PEM as a mandatory symptom for ME/CFS. This is evident in the Canadian consensus report, in the ICC report, in the IACFS/ME Primer, and in the letter to the secretary of HHS signed by 50 experts (https://dl.dropboxusercontent.com/u/89158245/Case Definition Letter final 10-25-13.pdf). In the letter, the experts state:
"Unlike the Fukuda definition, the more up-to-date CCC incorporates the extensive scientific knowledge gained from decades of research. For example, the CCC requires the symptom of post-exertional malaise (PEM), which researchers, clinicians, and patients consider a hallmark of the disease, and which is not a mandatory symptom under the Fukuda definition."
In the letter the experts point out that new, wide definitions can move the development backwards. I believe this is exactly what CDC is contributing to by stating that PEM should not be a mandatory symptom for ME/CFS.

I agree that people with other similar symptoms but no PEM should also get proper health care and research, but I think the gain achieved in this matter by keeping them included in the ME/CFS definition is much smaller than the risk for the ME/CFS population caused by new sets of criteria which will, compared to the CCC, again broaden the patient group, making it more heterogenous.

Bob, I think you have a good point in that the second best thing with regards to CDC would be to get Dr Unger to make clear subgroups with and without PEM. But I think the very best thing would be to stick to the development created by our experts and keep PEM as a mandatory symptom for ME/CFS (I would love a new name) and then group those without PEM in a different disorder. CDC is not the only "decider" in this, right? So in the advocacy aimed at for example IOM and the P2P people I think we should still keep the position that PEM should be a mandatory symptom for ME/CFS, as stated in the consensus documents and in the letter signed by the leading ME/CFS experts.

And I completely agree with Neilk and Bob on this:
In addition, since when do we have to conform our set of criteria based on what is easily understood by regular clinicians? --
Perhaps that's the link that I've been missing from this discussion.
Beth Unger wants to have a definition that is easily workable by a general practitioner.
But we need clinical centres of excellence where patients are diagnosed and treated by experts.
That would surely solve the problem that Beth Unger highlights.

 

[Nielk]

@Anne - I completely agree with you that Unger's data is from the multi-center study. Most of the experts in this study are using the CCC criteria, so of course the odds are high that they will suffer from PEM.

This is really a vicious cycle.

In addition, wouldn't that argument call for an inclusion of PEM - if most patients actually do suffer from them.

You state:

I also received an e-mail from Dr Unger, and I, too, was disappointed by her reply. She maintains the position that PEM should not be a mandatory symptom for ME/CFS, but she doesn't answer my questions about the logic behind this (Only symptoms that are easily measurable with current medical technology can be a mandatory part of a case definition?) and she doesn’t mention how this applies to the other typical symptoms of ME/CFS. Fatigue/fatiguability, muscle pain, joint pain, sore throat, headaches are surely all as hard to identify or quantify in a standardized way as PEM? If there are validated ways of self-reporting these symptoms, then it is of course possible to create a standardized way to report PEM as well.

It leaves one wondering - why is Unger so keen on leaving PEM out? What is her motive?

You continue..

In the letter the experts point out that new, wide definitions can move the development backwards. I believe this is exactly what CDC is contributing to by stating that PEM should not be a mandatory symptom for ME/CFS.

I agree with you 100%!