FROM THE CFS NEWSWIRE: Dr. Nancy Klimas, M.D. Talk on CFS
X-To: cfs-wire@stjohns.edu
POSTED BY: Camilla Cracchiolo
AUTHOR: Camilla Cracchiolo
COPYRIGHT NOTICE: None
[The following summary was provided by Camilla Cracchiolo, R.N. who attended the May 12 lecture sponsored by the Irvine Center for Special Immunology.]
Immunologist Nancy Klimas, M.D., a researcher at the University of Miami, spoke about Chronic Fatigue Syndrome in San Clemente, CA on May 12. Daniel Prince, my husband Robin, and I attended the lecture. Dr. Klimas is not only one of the leading researchers into CFS in the U.S., she is very well respected for her AIDS research.
Audio and video tapes of the lecture are available from:
The Center for Special Immunology
100 Pacifica, #100
Irvine, CA 92718
Attn: Joyce Swaving(714) 753-0670
They didn't know the exact cost before we left the conference, but they said they were offering the tapes 'at their cost' and it would probably be in the $15-$20 range.
I'm going to give a full report, but first let me list the new things that she said.
She prefers the labs at the University of Miami and says that physicians don't need to be directly affiliated with the medical center to submit specimens.
Over 90% of the people with CFS type symptoms have definite immune abnormalities. In the other 10% she says she 'looks real hard for some other cause of the symptoms'.
Treatment
is symptomatic. Treating sleep disorders is important. She
discussed the alpha intrusion in sleep and said that rather than
the poor sleep causing the myalgia, she thinks it may be the
other way around; pain causing poor sleep. Therefore, she thinks
pain control is very important.
Half
of all people with CFS develop concurrent depression. Very
important to treat this.
Anti-retrovirals
are very dangerous and completely inappropriate in CFS.
Ampligen
'had a good placebo controlled trial' and showed significant
clinical improvement when studied, but no one can get it because
the company is not making it anymore.
Acyclovir
failed to help in the Straus study. She would like to see a study
using acyclovir IV in high doses on the subset of people with CFS
who also have high HHV-6 titers. It may also be helpful to
patients whose flares are prodromed by herpes cold sores.
Cognitive
symptoms are the most bothersome problem to people with CFS; it's
the second most common complaint in most studies. In a few CFS
studies, it's the most common complaint. She believes that
cognitive rehabilitation exercises with a good psychotherapist
are of benefit.
SSRIs
(Prozac, et al.) were the first drug she studied. She considers
it the first line drug. She did a study comparing depressed and
non-depressed people with CFS. The non-depressed CFS patients
benefitted the most; and you could see improvement in natural
killer cell function as well. She believes that SSRIs have an
effect on CFS other than anti-depressive. (This study was
published sometime last year; I didn't get the reference). Low
dosages can be helpful; since you are aiming for it's immune
effects you're not necessarily trying to cross blood/brain
barrier, therefore you may not have to go as high as full anti-depressant
dosages. She starts at 2 mg and works up slowly. The effects may
not be noticable until after *four months* of therapy; the usual
3-4 weeks is not enough time to effect immune changes. She gives
it a 6 month trial before changing drugs.
Interferon
alpha makes you feel lousy. Pilot study in Lancet on 15
patients showed only 1/3 improved, but the improvement in that
group was dramatic, from bedridden to back to work. It may be
beneficial for a selected subset of people with CFS; this is one
of the things she wants to study.
Interleukin-2
makes you feel worse than Interferon alpha; she's not using it.
Interleukin-12
is very exciting; Used to be called 'Natural Killer Cell
Stimulating Factor' before it was renamed Interleukin-12. She is
trying very hard to get some for a CFS trial; it's only now
starting to go into clinical trials for HIV.
Cytokine
inhibitors: Her team thinks Tumor Necrosis Factor is one of the
key cytokines in CFS; A TNF inhibitor is available called Trental
(pentoxifylline). She is starting a placebo controlled trial on
this. (For lay people reading this: Trental is a drug commonly
used in the treatment of a vascular problem in the lower leg
called intermittant claudication.)
Immunoglobulins:
The studies on IgG are contradictory. Peterson's study of it here
in the US was negative, but Lloyd's study in Australia was
positive. The Lloyd study apparently used much higher doses of
IgG and suggests that giving high doses of IgG during CFS flares
may be beneficial. She's critical of the studies (or at least
Peterson's; it was a little hard for me to figure out exactly
what she was referring to here) as not selecting out for people
with B cell and antibody defects. She calls it 'fatally flawed'
and says it needs to be repeated. She recommends that physicians
seeing people with CFS try IV IgG on patients who have B cell or
antibody production problems *and* who are getting repeated
bacterial infections to see if it helps them.
Also
she mentioned thalidomide, but I'm sure if it was as a cytokine
inhibitor or not.
Allergy
shots: She feels they aren't harmful to people with CFS and may
be helpful *if* the proper precautions are taken. She
recommends starting out at extremely low dilutions, 1:10,000, 1:100,000
or even lower. She also thinks that the dosage should be
increased at half the rate allergy shots are for people without
CFS.
The lecture was part of an all day program sponsored by the Center for Special Immunology, with special thanks to the CFIDS Association of America. We drove 60 miles to get there and couldn't stay for the entire program, which included their own physicians, and workshops. But we did hear Nancy Klimas and Linda Iger-Miller.
Dr. Klimas is also working on Gulf War Syndrome.
She expects that the CDC definition is going to change to make it more inclusive. The new physical criteria were supposed to be announced at the recent conference on Gulf War Syndrome, but it wasn't. She thinks we people with CFS need to fight for a good definition for disability; the case definition was never intended to be used for clinical diagnosis.
As to clinical purposes, she sees no need to exclude people from a diagnosis of CFS who have other medical conditions, if the medical conditions are of long standing, stable, and would not reasonably produce CFS type symptoms. Example: hypothyroidism that started many years ago that has been properly treated. Or a person who had a one episode of reactive depression many years ago.
She sees the steps involved in developing CFS as follows:
Genetic Predisposition
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Etiologic Event
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Immunologic Response
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Perpetuating Factor
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Health Outcome
1. Genetic Predisposition: she talks about a small study she did on tissue typing on 110 people with CFS compared to 1600 normal controls that she did. (She notes that 110 people is considered a small sample size for genetic studies). She found:
2. Etiologic Agent: This is 'the black box' of CFS research. No longitudinal trials of people with CFS going on. She talked about how Epstein-Barr virus was finally identified based on the blood of one woman who was a lab tech and had stored her serum as normal controls for years before she became ill. When this woman came down with mono, they were able to study her blood from before the illness. We don't have that with CFS. The alternative is a long term longitudinal study, that follows people for years and sees who gets CFS.
Possible etiologic agents: Her model of studies assumes that the cause of CFS is either something 'profoundly immune activating or profoundly immune suppressing'.
Possibly activating agents include:
Possibly immune suppressing agents include:
All started out about 80% of normal immune function, whether HIV - or +.
Exercise group showed the most profound effects, with all participants returning to 100% of normal in 6 weeks, regardless of HIV status. Lymphocyte counts rose at least by 100.
Relaxation group also returned to 100% of normal but it took about 12 weeks.
The control group dropped down to 50% of normal regardless of HIV status just from the stress of not knowing their test results. They were told their HIV results after this. The HIV neg men gradually rose back to the 80% baseline; the HIV + men dropped even further and stayed down.
In other words, chronic stressors can have profoundly suppressant effects on the immune system. However, CFS is *not* a stress disease; almost all people with CFS have contact with some infectious agent at onset as well.
Whatever it is, we know it's not inflammatory enough to make a sed rate rise significantly, but all rheumatologic illnesses need to be thoroughly ruled out. 20% of her patients have autoimmune thyroiditis (Hashimoto's Thyroiditis). She suggests that there may be some autoantibody being produced that we don't know about yet. Very important to rule out MS and Reiter's syndrome. Mentioned Fibromyalgia studies and serotonin antibodies.
Endocrinologic factors may play a part in this. (She mentions Demitrack's work on the hypothalmic-pituitary-adrenal axis).
Most people report onset with a flu-like illness. Three possibilities for a virus:
Here in US we look a lot at herpes family viruses, like EBV, CMV, herpes simplex I & II and HHV-6. In Europe, more attention is being given to coxsackie virus and enterovirus. She said "It would be very interesting indeed if coxsackie virus turned out to be the culprit'.
Other possibilities are bacteria and parasites.
3. Immunologic Response:
Here's what's happening:
She has found that the severity of the illness correlates to the levels of cytokines and cell function.
She thinks researchers may finally have identified which cytokines can distinguish various groups of patients and how severe their symptoms are. These are: Interleukin-1 and Tumor Necrosis Factor. Interleukin-4 and Interleukin-6 are allergy related. and Il-6 stimulates autoimmunity as well.
Theraputic interventions have to be directed either towards calming down cytokines or activating cellular function.
She has great reservations about using cortisone to treat this.
Psychoneuroimmunological interventions may be beneficial.
She did a study after Hurricane Andrew hit Florida between people woth CFS who lived in affected counties and people who didn't. People in the affected counties had more relapses, more severe symptoms and relapsed for much longer periods of time. Many are still not recovered.
For those of you who like to look up the studies yourself, attached below is a partial bibliography of Dr. Klimas' work.
CFS related work:
Non-CFS work referred to in the report above:
Any comments? Send them to Bill Jackson at cfsdays@yahoo.com
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