Hello I'm Dr. John Iskander.
Welcome to CDC Beyond the Data.
I'm here today with Dr. Anthony Komaroff, Professor of Medicine
at Harvard University.
Thank you very much for joining us today.
My pleasure John.
Dr. Komaroff, at today's session, the focus was
on a disease often commonly still referred
to as chronic fatigue syndrome.
You've written very articulately
about what CFS is and what it isn't.
Can you just start with your perspective on that?
Sure. Well, what it isn't is the common periods of fatigue
that nearly every human being experiences.
It is a very unusual prolonged and debilitating state
of fatigue with a group of other symptoms.
I think the cardinal parts
of the illness are what's called post exertional malaise
where any kind of effort physical
but also mental makes all
of the symptoms worse following that effort.
Typically about 12 to 48 hours afterwards.
The second big part of the illness is cognitive problems.
The third part is un-refreshing sleep.
People who basically never awaken feeling rested even
if as far as they know they had a good night sleep
and slept for many hours.
So, and the last manifestation is orthostatic intolerance,
people whose symptoms are made worse by standing up
and maintaining an erect posture
and whose symptoms improve if not being fully abolished
by lying flat or putting their legs up.
Those, those are the cardinal manifestations.
So clearly what you just described differs significantly
from, as you say, as ordinary fatigue or fatigability.
What do we know about how common CFS is in the population?
It depends, there've been different case definitions
of CFS and depending on which ones you use you get somewhat
different answers.
I think the best answer is in a range of between four
and eight per thousand adults.
But it's higher in women adults and it's, appears
to be somewhat lower in children who get this illness as well.
So, not an exceedingly rare condition.
No.
Have we through, through research developed some
hypotheses about what some of the triggers or risk factors
for this disease might be?
We know that many but not all patients with the illness,
in my experience the majority, say, "I was perfectly fine
until one day and I came down with this flu"
or whatever they describe, an infectious like syndrome
with aching muscles, fever, swollen glands, gut symptoms,
neurologic symptoms, and they say
"that acute illness got somewhat better,
but I feel I have never recovered from that.
Now it's months and years later".
So that, it suggests that, at least for some people,
many people, there may be an infectious trigger.
Whether any infectious agent,
but no infectious agent has been convincingly tied
to this illness and I think it remains very uncertain whether
an infectious trigger also goes
on to perpetuate the symptoms that,
that I think we don't have much evidence for so far.
Yeah, so we heard today, actually I think
that about three quarters of cases may be preceded
by some type of infection.
We also heard from the National Institutes of Health
about a research study
that they're planning looking specifically at individuals
with post infectious CFS.
What might we hope to learn from that kind of research?
Well I think the biological research that's been done
so far, and an enormous amount has been done
in the last 30 years or so
that I've been involved with this illness.
There's now over 9000 published articles and they point
to abnormalities of the central nervous system,
autonomic nervous system, immune system, and energy metabolism.
And so I expect that the NIH studies will,
will find some of the same things.
Hopefully they will find a few additional things including
if they're lucky and we're lucky a true pathologic gold standard
biomarker for the illness because we lack that now
and if you don't have that, it's awfully hard to say
to anyone you have this illness definitively and it's very hard
to test the validity of any case definition
without a gold standard biological marker against which
to test that definition.
It's very, very interesting.
So again we, we have very strong evidence
for underlying biological processes.
We're still in the process of trying to translate those
into biomarkers or diagnostic tests.
Right, by which I mean in a biological abnormality that has
such a low false negative rate and low false positive rate
that it constitutes a good diagnostic test.
That we don't have.
Plenty of biomarkers that clearly
and statistically significantly distinguish cases from controls,
healthy controls but also control subjects
with other fatiguing illnesses but none of those is
so sensitive and so specific
that it is an adequate diagnostic test.
Okay, certainly.
Dr. Komaroff, you referred to the fact
that there have been many, many thousands of these studies done
on chronic fatigue syndrome,
much of your presentation today focused on a recent report
from the Institute of Medicine which tried to synthesize a lot
of that. Can you summarize
for our audience what were really some
of the key take-home findings
from that very comprehensive review?
Yes, it was a Herculean task.
This panel of, I think, about 25 scientists,
different disciplines, reviewed each
and over 9000 published articles and they concluded
that there was lots of evidence using different technologies
of central nervous system problems,
autonomic nervous system problems,
and that includes cognitive deficits
that are objectively measurable white matter problems,
evidence of neural inflammation using ligands
with pet tracers that light up in inflamed areas of the brain.
Immune system abnormalities, the two most robust of which
in their review were natural killer cell dysfunction
that correlated with illness severity and elevated levels
of various cytokines in the periphery typically in the blood
that suggest the state of chronic immune activation.
They also, I believe, proposed a new case definition
which you alluded to earlier.
They also proposed a new name for this condition.
Could you tell us a little bit
about why a new name might be needed?
Sure. I think the name that this illness has been called
by most often, chronic fatigue syndrome, was really coined
by a group organized by CDC back in the late 1980s and the focus
of the group was on creating a case definition.
I was part of that group.
None of us was even thinking about the name
and when the name chronic fatigue syndrome was suggested
everyone said, "sure", "why not?"
I think that was a big mistake because the name in my opinion
and the opinion of a lot of people is, it both trivializes
and stigmatizes the, the illness.
It makes it seem unimportant.
Maybe not even real
so people have looked for a better name.
One that, that doesn't do that.
This committee proposed,
Systemic Exertion Intolerance Disease,
because exertional intolerance is a,
is a core feature of the illness.
Whether that new name will take with the professional community
and the patient community, I think we still don't know.
So, so let's come back to the patient.
We really tried to make that the focus of this session.
What are the prospects for patients in terms of recovery,
we know we do not have any definitive cure
but what are the prospects for, for treatment
and recovery for patients?
For recovery there aren't a lot of systematic long-term studies
to address that question.
My synthesis of those that do exist,
in my own personal experience caring for hundreds of people
over 30 years, is that most adult patients,
in my experiences with adults, have a terrible first year
and then have some improvement thereafter.
Whether it's true improvement or an improved ability to cope
with the illness, hard to tell.
About 5 to 10% of patients return
to what they feel is a fully normal state.
Only 5 to 10%.
And a substantial fraction of those will have a relapse.
So, although I wish it were different, I think the majority
of patients will, at least if our experience
over 30 years is a guide, are not going
to fully recover absent the really important discovery
and new treatment.
So we heard today that for pediatric patients perhaps their
long-term prognosis may be a bit better but...
Yes.
What are some of the things on the horizon that,
that offer hope, that offer grounds for, for optimism
for patients with this disease
and for clinicians caring for these patients?
I think the greatest grounds for hope is
that when this disease was first resurrected,
I think the disease actually has been discussed
in the medical literature for centuries
but the renewed interest beginning in the mid-1980s
at that time no one knew anything about it,
the biology of it and no one in the world was working on it.
Now laboratories all over the world are working actively
to try to figure the disease out and have discovered
as we discussed a lot of clear biological abnormalities
that are bound to allow us someday, and I hope it's soon,
to find definitive treatments, interventions
that make people a lot better.
Just the fact that so many distinguished scientists are now
actively spending a lot of time working on this problem is,
I think, should be grounds for hope for everybody.
And we'd certainly count you as one
of those distinguished scientists.
Thank you.
Thank you very much Dr. Kamaroff.
Please join us next time for
Beyond the Data.