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WHO GETS FIBROMYALGIA?
Although
the exact cause of fibromyalgia has yet to be clearly elucidated, several
risk factors have been identified that make one more prone to developing
the syndrome. Unfortunately, most of these factors are non-modifiable
(such as gender, age and family history). The important thing to remember
is that although you may not control whether you acquire fibromyalgia, you
have several treatment and coping options available to you that can
greatly improve the quality of your life. The major risk factors for
fibromyalgia include:
Gender - Fibromyalgia occurs between 70% and
90% more often in women than in men. The exact reason for this remains
unknown. If you are a man and think you may be affected by fibromyalgia,
see the section on Men With Fibromyalgia.
Age - Fibromyalgia is
most commonly seen in the women of childbearing age. Thus, it normally
develops between the ages of 20 and 55; however it has been known to occur
in children also.
Sleep Abnormalities - As will be described more
clearly below, it is not known whether disturbed sleep patterns predispose
one to developing fibromyalgia, or if they are just one of the many
symptoms associated with fibromyalgia. Either way, sleep problems and
fibromyalgia are closely related and if you have one, you are more likely
to have the other.
Family History - It has been shown that you are
more likely to have fibromyalgia if someone in your family (such as your
mother) has been previously diagnosed with the condition.
WHAT CAUSES FMS?
The cause of fibromyalgia remains elusive, mainly because
there are no physical examination or laboratory findings suggestive of a
specific diagnosis. Further, muscle biopsies taken from the tender points
of fibromyalgia sufferers are inconclusive for any tissue abnormalities
specific to fibromyalgia. However, researchers have several theories about
causes or triggers of the disorder. A few examples would be an infection,
a car accident, and the presence of rheumatoid arthritis, lupus or
hypothyroidism. These injuries may affect the central nervous system.
Fibromyalgia may be associated with changes in muscle metabolism, such as
decreased blood flow, causing fatigue and decreased strength. Others
believe that fibromyalgia is triggered by an infectious agent such as a
virus in susceptible people, but no such agent has been identified. Even
if these things don’t necessarily cause fibromyalgia, they may cause
changes in your body that can predispose you to a developing
fibromyalgia.
Since it is believed that there is not’t one
single cause of fibromyalgia, a number of factors must contribute. These
factors may include:
Autonomic Nervous System
Dysfunction
The autonomic nervous system is the portion of
the nervous system that controls the function of the different organs and
systems of the body. For instance, it regulates body temperature, blood
pressure, heartbeat rate, and bowel and bladder tone. It is called
autonomic because it is something that our body does automatically since
we don’t consciously control these things. The autonomic nervous system
works closely with our hormonal system and neurotransmitter system and it
is particularly involved with something referred to as the
hypothalamic-pituitary-adrenal axis.
The autonomic system is
divided into two branches: sympathetic and parasympathetic. The
sympathetic system prepares in response to stress or emergencies while the
parasympathetic system favours digestive functions and sleep. The action
of these two branches of the autonomic nervous system is by something
called neurotransmitters and hormones. Dysfunction in the autonomic
nervous system is manifested in abnormalities in the levels of
neurotransmitters, hormones and abnormal action of the
hypothalamic-pituitary-adrenal axis. These are discussed
further.
Neurotransmitters
Neurotransmitters
are the substances that nerves in the autonomic nervous system use to
communicate with each other. They are the vehicles that carry information
back and forth between your body and mind. Certain neurotransmitters such
as serotonin, substance P, and beta-endorphins have all been studied
looking for causation.
Substance P
Several
different studies have shown that substance P – a neurotransmitter that
causes pain to be felt – is elevated threefold in the spinal fluid of
patients with fibromyalgia. Substance P is composed of 11 amino acids and
elevation of this neurotransmitter leads to an enhanced pain perception.
Thus, for the same painful stimulus, a person with higher levels of
substance P will feel more pain than another
person.
Endorphins
Recent studies have looked
at the neurotransmitter beta-endorphin in the immune cells of patients
with fibromyalgia. Beta-endorphin is the opioid produced by the body to
fight pain. It is also involved in stress responses, pain suppression, and
mood disorders. Interestingly, high beta-endorphin levels in the brain
suppress the immune system. One study found that the beta-endorphin levels
of fibromyalgia patients is close to half that of the healthy population.
Therefore, in the future, beta-endorphin levels may be used as a
diagnostic tool or to monitor treatment of patients with
fibromyalgia.
Serotonin
Some studies suggest
that fibromyalgia sufferers may have decreased levels of the
neurotransmitter serotonin which is linked to depression, migraines and
gastrointestinal distress. Most antidepressant medications raise levels of
serotonin explaining low doses of these drugs help some patients with FMS
(see section below on Treatments for Fibromyalgia for more information on
antidepressants as a treatment for
fibromyalgia).
Neurotransmitters and
Medications
When taking medications for fibromyalgia it is
important to discuss with your health care provider whether the
medications will alter neurotransmitter levels. In some instances, drugs
prescribed for fibromyalgia can actually alter the neurotransmitter levels
even more, worsening your condition.
Hormones
·
Cortisol
Hormones have also been studied in order to uncover
if any abnormalities exist in the levels of various hormones of
fibromyalgia patients. Two specific hormones that have been shown to be
abnormal are cortisol and growth hormone. Cortisol is released by the body
in times of stress, both physical and mental. It can partially explain why
fibromyalgia patients feel constantly “off” or “drained”.
·
Growth Hormone
With growth hormone the problem seems to be
underproduction. Normally, during exercise and during sleep the body is
supposed to produce a several fold increase in the production of growth
hormone. In fibromyalgia, the autonomic nervous system responsible for the
release of growth hormone is under-responsive and the required increase in
the hormone is not seen. Growth hormone has a powerful effect on the
connective tissues in your body. It directly stimulates vital cellular
products such as fibroblasts, mast cells, ground substance and collagen
fibres. It is important in wound healing because it is the rapid
production of collagen fibres by fibroblasts that is necessary for repair.
Growth hormone is normally released during deep levels of sleep but people
who suffer from fibromyalgia have this level of sleep disrupted and
therefore have very low levels of growth hormone. This can lead to a
decreased repair response, decreased immune response and fibromyalgia
symptomatology.
· Norepinephrine
Norepinephrine
is a hormone that is released by a part of your autonomic nervous system
known as the sympathetic system. By releasing this hormone and controlling
the release of epinephrine via the adrenal gland, the sympathetic nervous
system is able to control your bodily functions that are not’t under
conscious control: heart rate, blood vessel contraction, sweating,
salivary flow, intestinal movements, and even the little hairs on your
arms. As with growth hormone, fibromyalgia patients seem to suffer with
reduced levels of epinephrine responses, especially in response to low
sugar levels or exercise. Abnormal levels of norepinephrine will cause
symptoms to be felt all over your body. These symptoms may manifest as the
chronic fatigue and pain associated with
fibromyalgia.
Hypothalamic-Pituitary-Adrenal Stress
Axis
Recent studies have shown that this axis that lies in
the brain may have a role in the development of fibromyalgia syndrome.
Among other things, the hypothalamic-pituitary-adrenal axis (HPA) is the
part of your brain that deals with how your body handles stress, both
physical stress and psychological stress. Many patients with fibromyalgia
report the onset of their symptoms after a significant period of emotional
stress or a specific traumatic event. Fibromyalgia sufferers also report a
higher level of daily stress and that their symptoms are significantly
aggravated by stress. This points to over-activation of the HPA axis as a
possible cause of fibromyalgia. Actually, most of the symptoms associated
with fibromyalgia, such as sleep disorder, headache, and irritable bowel
can be traced back to increased activity of the HPA axis. Curiously,
studies have shown that the main stress hormone that is secreted in the
HPA axis in response to stress – cortisol – is lower than normal.
Therefore whether it is over activity or underactivitiy of the HPA axis is
not entirely clear. What is clear is that there is an alteration in the
HPA axis and more research is required to identify the precise nature of
this alteration.
Sleep Disturbances
Some
researchers theorize that the sleep disorders seen with fibromyalgia may
actually be a cause, as opposed to symptom – of the syndrome. Stage 4
sleep is the deepest level of sleep and is the one that is most lacking in
fibromyalgia sufferers. Evidence that sleep disturbance may be a possible
of fibromyalgia was given by a study that was able to induce
fibromyalgia-like symptoms in normal volunteers by depriving them of deep
sleep.
It is during stage 4 sleep that a hormone called somatomedin
C is released into the system. Without enough deep sleep, fibromyalgia
sufferers show abnormally low levels of this hormone which is essential
for the body to rebuild itself. Lack of this hormone may be causing the
characteristic muscle pain and fatigue commonly seen in fibromyalgia.
Also, release of growth hormone occurs primarily during stage 3 and stage
4 of non-REM sleep. Thus disturbed sleep will affect the release of this
hormone causing abnormalities in your body. One third of patients with
fibromyalgia have low insulin growth factor (IGF) levels, an indication of
low growth hormone secretion. Interestingly, amongst fibromyalgia
sufferers, the severity of the sleep disorder seems to correlate with the
number of tender points they have (see below for an explanation on tender
points).
Sleep deprivation is also known to cause some of the
symptoms involved with “fibrofog.” People who lack enough sleep or poor
deep sleep have been known to experience feelings of being in a fog, loss
of control of though processes and poor memory.
Studies have shown
that exercise increases the amount of time spent in deep sleep. Thus, it
is not surprising that exercise has been confirmed to be of value in the
treatment of fibromyalgia. See the section on Treatments for more
information on appropriate exercise regimens.
Injury or
Microtrauma to Muscles
It has been suggested that the pain
of fibromyalgia may be related to microtrauma in deconditioned muscles and
that exercise helps fibromyalgia sufferers by conditioning these muscles.
For example, pain in the muscle causes spasm in the muscle, causing more
pain, which in turn causes more spasm. The muscle becomes chronically
congested, and the delivery of oxygen and other nutrients, as well as the
removal of metabolic wastes and acids, becomes impaired.
A
recent study looked at the relationship between neck injuries and the
onset of fibromyalgia. It found that fibromyalgia was 13 times more likely
to occur following a neck injury than an injury to the lower
bodies.
However, muscle biopsies have not been able to
identify any difference in sore muscles when compared to other non-tender
parts of the body. Also, some tender points are not over muscles or
tendons but over bones or fat pads. Scans of fibromyalgic muscle tissue by
electron microscope have revealed some abnormalities in the levels of a
muscle sugar called glycogen. Abnormal organelles called mitochondria that
are involved in energy production have also been found in fibromyalgia
patients. So while there is some evidence that abnormalities in the
metabolic properties of the muscles may be involved in fibromyalgia, it is
more probable that these injuries to muscles don’t cause fibromyalgia, but
rather, they may awaken a hidden genetic predisposition.
Another
way whereby injuries may be involved with fibromyalgia is that an injury
to the upper spinal region may affect the central nervous system and may
trigger the development of fibromyalgia in some people. The brain is
easily overwhelmed by head injury, viruses, and severe stress. When an
injury to the brain occurs, it triggers a cascade of biological events
involving neurotransmitters, hormones and changes in blood flow, to
protect the traumatized area. Unfortunately for the patient, such
defensive action by the brain can cause serious problems in the body. Some
of the things that they can cause are many of the same symptoms that
fibromyalgia patients may be suffering from. Several studies are currently
analyzing brain wave activity to see if there are differences between
normal people and fibromyalgia sufferers.
Other Possible
Causes
Other less frequently theorized causes
include:
Central nervous system dysfunction. Some believe
that fibromyalgia sufferers have an abnormal nervous system that leads to
abnormal processing of sensory stimuli. This means that the patient’s
nervous system processes normally non-painful sensory stimuli as being
painful. This phenomenon in which pain results from a stimulus that should
not normally be painful is known as allodynia.
Changes in muscle
metabolism, such as decreased blood flow, causing fatigue and decreased
strength.
Infectious agents such as a virus but no such agent has
been identified. Also, if fibromyalgia were infectious we would expect so
see an increased incidence in spouses of an affected patient and this is
not the case.
Immune system abnormalities. Several changes in
immune system function have been found in fibromyalgia, generally in the
direction of increased activity. Hyperactive immune system symptoms can be
induced in normal volunteers through sleep deprivation. This may link
sleep dysfunction and immune function as causative agents in
fibromyalgia.
Muscle tension. Muscles that are in a chronic state
of contraction will not relax fully, even with rest. Muscles constantly
taxed this way can produce an unlimited variety of unpleasant symptoms. It
should also be noted that contracted muscles not only cause the brain to
release certain chemicals that can cause pain, but that they greatly
restrict the oxygen that they take in, which can produce drastic side
effects since oxygen is responsible for regulating the fluid levels in
soft tissues as well as repairing injuries.
Tense muscles can also
press adjacent nerves, causing pain, tingling and numbness. Stressed
nerves can create weakness in affected muscles and restrict motion in
nearby joints. A muscle’s constant state of contraction will cause it to
shorten, limiting motion and causing muscle aches and
stiffness.
Genetic predisposition. Although no specific inheritance
pattern has been identified, an increased incidence in relatives of
affected patients had been noted. Therefore, development of fibromyalgia
may involve certain predisposing factors that are inherited, as well as
precipitating factors such as trauma, infection, stress or sleep
disruption. Current studies on twins with fibromyalgia are examining the
possibility of genetic predisposition to the syndrome.
Current
research is looking that the significance of spinal stenosis (narrowing of
the spinal canal) or Chiari malformations and fibromyalgia.
MEN WITH FMS
Although fibromyalgia is much more prevalent among women –
roughly three times more – it can also affect men as well. Although it is
more common among women, a recent study has indicated that the symptoms
that men who suffer from fibromyalgia experience may be more severe. The
study also stated that men may sufferer a greater amount of physical
dysfunction and a lower quality of life.
Being male and dealing
with fibromyalgia may be even more difficult. You may feel isolated, of be
the only male in a support group. Also, men may have a difficult time
getting a proper diagnosis and treatment since fibromyalgia is generally
thought of as a “women’s disease”. If you are a male and suffering from
fibromyalgia you are not alone. There are several support groups available
and the treatments listed on this website are effective for both man and
woman. Here are some additional tips for males suffering from
fibromyalgia:
· Set realistic, obtainable goals and ones which can
be achieved on a daily basis. This will prevent you from pushing yourself
beyond your physical capacities.
· Don’t keep your feelings or
suffering a secret. By expressing your concerns you will allow others to
assist you in your journey to a healthier you.
· Join a support
group. Many people are surprised how readily they are accepted and how
reassuring it is to know that there are others out there dealing with the
same issues they are. Further, support groups often provide valuable
coping tips and strategies from other fellow fibromyalgia
sufferers.
· Understand that you are not as powerless as you feel
or fear. While it may feel like that now, you have complete control over
how you deal with fibromyalgia. Many of the treatment and coping tips
including on this website are things you can do on your own to assist you
in regaining absolute control over your life.
Evidence for The Organic Basis of
Syndromes
Chronic Fatigue Syndrome, Fibromyalgia and Associated
Syndromes: Evidence for Their Organic Basis
11-01-2002
Excerpt: A summary of the suggested underlying pathophysiologies
and treatment approaches
By Dr. Andrew J. Wright, MBChB, DRCOG, MRCGP,
DCH, DIHom
Foreword
I have written this
document in order to share information with colleagues and patients. It is
a technical paper but I hope to produce a lay readership version as soon
as time allows. My experience in this field is based on more than 10 years
of treating a large number of patients in primary care, general medical
out-patient clinics, and in private practice. I am one of the Medical
Advisors to Action for ME, a charity involved in helping patients and
their caregivers. I also sit on the research group of that charity. The
charity has recently financed a literature and evidence search to obtain
as much information as is currently available about this group of
illnesses. I have collaborated in that research. I was also a member of
the Reference Group of the Chief Medical Officer’s Working Group on
Chronic Fatigue Syndromes.
Organic vs. Psychiatric
Model
I am a firm advocate of the organic basis for these
illnesses. I feel the psychiatric/psychological models of the illnesses
are incomplete and unable to explain the underlying pathophysiology. I
fully accept that psychological difficulties arise in these illness, but
only at the same frequency as in any other chronic illness. I also accept
that psychological/psychiatric type interventions can help those patients
who are in need of them.
Antidepressants may help pain. They can
alleviate depression, where it exists, and increase a sense of well being.
Some patients derive good benefit from cognitive behavioral therapy (CBT),
if psychological problems co-exist with their illness. I encourage CBT in
those who are in need of it.
Some studies do show that a sub-group
benefit from graded activity, but only when experts in the field
administer that treatment. Others studies show no sustained improvement
and high drop out rates. However, many of these studies are based on the
Oxford Criteria, where the only essential requirement for inclusion is
fatigue. This is different from the 1994 CDC criteria that requires many
more of the wide range of symptoms you commonly find in patients.
The best advice is often to do less, not more. Giving general
advice to simply increase aerobic exercises incrementally often makes
people worse. Exercise capacity is reduced. This is partly secondary to an
inability to achieve maximal predicted heart rate. This is thought to be
due to autonomic dysfunction. It is interesting how often people who are
so ill that they look as though they should be in a hospice, are told to
‘pull themselves together and go for a walk’. Surely, we have all been
taught to recognize when somebody is ill. Just because they are, 'Paper
Perfect People,' i.e., all our standard tests come back normal, does not
mean we should disbelieve them. It is possible of course that we may not
have done the right tests. I believe the evidence set out below shows this
to be largely true.
I feel the reasons for the dominance of the
psychiatric model is complex. Nonetheless, it is due in part to a way of
thinking that has been practiced by doctors for centuries.
Patient: attends with a set of problems. Doctor: doesn’t
understand and /or cannot help with the patient’ s problems. Solution:
make the patient the problem and then you can forget about their difficult
problems.
Although this is a simplification and might appear too
rhetorical it does often happen. Secondly is the lack of information
readily accessible about the organic basis of the illness. Many of the
research articles are published in journals that are not normally read
outside the researchers own specialty. This is one of the problems in
disseminating information about this group of illnesses. It is very
difficult to get articles published in the more popular journals, unless
they have a psychological bias.
As a consequence patients are then
often referred on to psychological services. This is not fair to the
majority of patients, or the psychiatrists/psychologists who are busy
enough.
Unfortunately, the overwhelming acceptance of this model
has led to patients' needs being largely ignored by the Health and Social
Services. This in many circumstances is the most difficult problem that
patients face. Not only do they have to suffer from the illness, but are
disbelieved by the Medical and Social Service professions and often suffer
great financial hardship. I am sure that this was never the intention of
those people who proposed the psychiatric model of this illness, but that
is what has happened.
Interestingly, psychiatrists working in this
field are becoming more cautious these days about labeling this as a
purely functional illness. They accept that the underlying pathologies are
not yet completely defined. They also caution about misdiagnosis. In a
recent paper by Deale and Wesseley, it was said that on review of patients
attending a Chronic Fatigue clinic around 68% of those with a psychiatric
diagnosis had been incorrectly labeled. There was no evidence of past or
present psychiatric disorder.
Also around 35% had psychiatric
disorders that had gone unrecognized. Therefore the use of scales such as
the Hospital Anxiety and Depression ratings are advised. This figure of
around a third with problems correlates well with any chronic illness.
In order to understand this group of illnesses, an awareness of
some of the newer specialties, such as Neuroendocrinoimmunolgy,
Chronobiology, Toxicology and Integrative Medicine has been important in
formulating these ideas. Some of the more controversial ideas emerging in
medicine are also described. You will not find the answers in your
undergraduate textbooks! The 'one disease, one diagnosis, one drug
approach,' does not apply with this group of illnesses.
The
evidence set out below is not comprehensive, partly because there has been
an exponential rise in research recently, which can only be good news for
sufferers. However this also this means that any overview is out of date
almost immediately after it has been completed. Up to date though,
charities, or individuals have paid for most of the research. Central
funding has been negligible.
Immunology and Toxicology
Some of the more striking abnormalities are those found in the 2-5
Synthetase/RNase L anti-viral pathway. These are not specific to CFS/ME
though, and abnormalities can occur in other viral illnesses. This pathway
works as follows: viruses activate the 2-5- synthetase enzyme. This in
turn converts ATP into 2-5 oligoadenylate and activates the RNase L
enzyme, which degrades viral and single stranded RNA. Various Protein
kinase enzymes also becomes activated and elevated, which again inhibits
both viral replication and protein synthesis. It has been suggested that
environmental toxins in the presence of heat shock proteins can also
activate this pathway.
Dr. Robert Suhadolnik, at Temple
University, showed as far back as 1989, that activity in this pathway was
upregulated in patients with chronic fatigue syndromes. Crucially in 1996
it was also noted that a proportion of patients had an abnormal version of
the RNase L enzyme. This low molecular weight form is 37kDaltons, compared
with the normal 80 and 47 kDalton versions. It was thought initially that
all chronic fatigue patients had this abnormal form.
The most
recent figures I could find by Dr. K De Meirleir showed that the low
molecular weight version was found in 680 out of 705 patients. The levels
quantitatively vary though, and the amounts correlate with the Karnofsky
Disability Index. The low molecular weight RNase L enzyme is up to six
times more biologically active and resists protein degradation. Therefore
when expressed, patients suffer an even greater depletion of ATP reserves
and inhibition of protein synthesis. It has been suggested that mycoplasma
genus cause the splitting of Rnase L.
The overwhelming fatigue
with an acute viral illness is due in part to ATP depletion in order to
fuel anti-viral pathways.
Unfortunately, to test for this enzyme
requires blood to be sent on dry ice to Belgium at present. Interestingly
studies have shown that those suffering from Fibromyalgia do not express
the low molecular weight RNase L. If confirmed by larger studies this
would be a major difference between the two illnesses.
This
upregulated system, either expressing RNase L or low mol wt RNase L can
then cause problems to varying degrees with enzymatic detoxification
pathways, particularly in the liver. It can monopolise protein synthesis
and deplete essential nutrients such as glutathione. Low white cell
glutathione is a feature of treatment resistant patients.
Some
very interesting and important work has come from Professor Vojdani, in
California. In 1998 he published a paper which showed that RNase L
inhibitor, the controlling enzyme in the 2-5 Synthetase/RNase L pathway,
is low in CFS/ME patients. This may be the underlying problem. The reason
this occurs is not yet known.
Vojdani suggests that measurements
of RNase L inhibitor and Protein Kinases can be used to show a viral
etiology and monitor relapses and remissions. Measurements of Protein
Kinase 1 are very important in studying the mechanism of interference with
signal transduction in lymphocytes. This signal transduction system
consists of eleven different isoenzymes, each having different biological
actions, and distinct abnormalities can be seen in CFS/ME patients. Also
important is measuring NK cell activity, which is often low.
Other
evidence on the importance of this upregulation and expression of the
abnormal enzymes has come from the use in patients of the agent Ampligen,
also called poly (1)-poly (C12U). This is a synthetic, mismatched
double-stranded RNA with potent anti-viral and regulatory properties. In a
double blind study involving 92 patients, measures of clinical response
such as cognitive functioning, exercise ability and less reliance on other
medications, improved in 80% of sufferers. The Karnofsky scale was used in
this study to measure the physical and social ability. Although rather
simplistic, it provides a useful functional guide.
Ampligen is
best given early in the illness, and in those positive for low molecular
weight RNase L. Not only does it have potent anti-viral properties, it is
also an immune system modifier, i.e. an allosteric modifier. It can
downregulate an activated immune system, as in CFS/ME, and upregulate a
depressed immune system, as in AIDS patients. Unfortunately Ampligen is
expensive, around £6-8000 per treatment. It also has to be given IV twice
a week. Relapses can occur on completing treatment and repeat courses may
be necessary.
Another interesting study by Vojdani, published in
1999, showed that not only could viruses elevate the above anti viral
pathway, but so could environmental pollutants, particularly Methyl
Tertiary Butyl Ether, (MTBE), and Benzene, components of petrol fumes.
Obviously many people are exposed to these toxins on a daily basis. He had
already shown that workers in the petroleum industry have toxicity
problems, especially high levels of apoptosis of cells. He took two groups
of patients with CFS /ME- 20 with viral genomes present on PCR testing,
but no history of chemical exposure or sensitivities, and 20 with
significant exposure to MTBE and benzene, but no viral genomes on PCR
testing.
In the same paper, Vojdani also showed that through the
use of MDBK cell lines, anti-Interferon-beta inhibited viral induction of
the antiviral pathways by 90%, but only 40% in chemical induction. Whereas
anti-Heat shock protein 70 inhibited 90% of chemical induction, but only
20% of viral induction. This suggests that proinflammatory cytokines are
implicated in viral induction, and heat shock proteins in chemical
induction.
A further study that looked at pro-inflammatory
cytokines showed that in a retrospective cross-sectional study, there was
a significant increase in serum TNFalpha, compared to controls
(p<0.0001). This raises the possibility of the use of
TNF-alpha-blockers, such as those introduced recently for Colitis.
These are chimeric anti-TNF-alpha antibodies, e.g. the monoclonal
antibody ’Infliximab’. It is interesting that in a study by Dr Buskila,
out of 113 patients with inflammatory bowel disease, 49% of Crohns disease
patients and 19% of Ulcerative Colitis patients satisfied the diagnostic
criteria for Fibromyalgia. Similar approaches are being tested in
Rheumatoid Arthritis. Maybe we can turn off the illnesses in their early
stages, before too much damage has been done.
Another Vojdani
study investigated the cell death rates in patients with CFS/ME. The study
looked at the induction of apoptosis in peripheral blood lymphocytes of
CFS/ME patients and controls, by the growth inhibitory cytokine
Interferon-Alpha. The apoptosis rate in patients was 26.6% n=29, compared
to controls 9.9% n= 15. This is similar to workers with increased
apoptosis secondary to environmental toxins.
A further toxicology
study by Dunstan showed that the amount of organochlorines in sufferers
was unusually high. He took patients and people who had been exposed to
organochlorines with similar clinical features. However, being exposed to
chemicals means that this group are excluded from the standard CDC
diagnostic criteria for CFS/ME.
Whilst talking about chemicals, it
is interesting to note that about 20-47% of CFS/ME and Fibromyalgia
sufferers complain of severe multiple chemical sensitivities. About 4-6%
of the general population also has severe chemical intolerance. The levels
of chemicals needed to trigger these problems would normally be considered
to be non toxic, however, host factors involving
sensitization/amplification of endogenous responses seem to be to blame.
Chemicals can sensitize the Limbic system directly via the Olfactory
nerve. The Limbic system then sends efferent messages to the hypothalamus
and the mesolimbic dopaminergic pathway.
Research to date has
shown that these sensitized pathways react unfavorably with exposure to
volatile organic compounds and pesticides, facilitating behavioral,
autonomic, endocrine and immune function dysfunction. This is seen by
sensitizability of cardiovascular parameters, resting EEG alpha-wave
patterns, betaendorphin levels and impairment of divided-attention task
performance. This fits in well with Professor Behan’ s work. It shows that
people exposed chronically to low dose organophosphates, who also have
CFS/ME, exhibit a neuroendocrine profile identical to acutely exposed
people. An example would be farm workers with 'sheep dip flu.' Here the
results of investigations looking at serotonin, acetylcholine and brain
glucocorticoid steroid receptor activity were identical in OP exposed
workers and those with CFS/ME.
Treatments
What are the most effective treatment protocols to date? Having
collaborated with Michelle Ranaghan, Action for ME’ s former Research
Officer, on the large literature search, I have read a lot of studies. I
feel the studies, with the fewest side effects and prolonged results on
follow up, are those using Integrated Medicine Protocols.
Crucially all the problems identified above are treated
simultaneously. Treatment is not only with conventional drugs, but also
with hormones, antioxidants and minerals, herbal preparations, nutritional
advice and sensible guidelines on rest and activity. Psychological
problems are also addressed.
One of these was by Dr. Jacob
Teitelbaum who published an open study showing promising results and
followed this up with a very well constructed double blind placebo
controlled trial, which has now been accepted for publication in the
Journal of Chronic Fatigue Syndrome. I feel this approach would be the
easiest to apply on the NHS.
72 Fibromyalgia patients, 70 of whom
also fulfilled the CDC criteria for CFS, were divided into two groups and
treated either with placebo therapies or active treatment by a unified,
simultaneous approach for three months. Patients were treated based on
clinical symptoms and/or lab testing for:
1. Subclinical thyroid,
adrenal (cortisol and DHEA), and gonadal hormone imbalances or
deficiencies.
2. Disordered sleep (Zolpidem,Trazadone, Amitriptyline,
Clonazepam, Melatonin or herbs such as Valerian root).
3. Suspected
neurally mediated hypotension with fludrocortisone and increased
fluids.
4. Opportunistic infections, e.g., common parasites such as
Blastocystis hominis, Giardia and Dientamoeba, Clostridia, and fungal
overgrowth with conventional antimicrobials and herbs.
5. Suspected
nutritional deficiencies (multivitamins, magnesium glycinate/malic acid,
B12 and Iron). 32 patients in each group completed the study. Using a
combination of patient and physician assessments, FMS Impact
questionnaire, Analogue scores and Tender Point Indices, the results were,
with p< 0.0001
The conclusion was that significantly greater
benefits were seen in the treatment, as opposed to placebo group, for all
primary outcomes. After one year, improvements had been maintained in the
treated group. Further details can be found at http://www.endfatigue.com
The
second impressive study was by Professor Majid Ali. This was an Open
prospective study on 150 Fibromyalgia/CFS/ME patients. The study was based
on the results of clinical, biochemical and video microscopy findings. The
program involved nutritional education, intravenous and oral nutritional
supplements, redox restoring substances, such as glutathione and taurine,
hormonal support, probiotic and herbal bowel therapies, nasal and other
oxidative therapies, gentle stretching and noncompetitive exercise, and
training in self-regulation and stress reduction. No attempt was made to
limit the number of therapies patients received. Neither was any attempt
made to blind the study, as this would have been impossible to do, given
the comprehensive and holistic therapies involved.
The patients were divided into three groups according
to duration of illness:
Group 1 < 3 years
Group 2 3- 6
years
Group 3 > 6 years
In conclusion, we have direct
evidence from good sources that these groups of syndromes share common
factors, and that there is proof for their organic basis.
In
CFS/ME) it seems that we should see this as an illness probably caused by
enteroviruses, acting on a body that is for many reasons already stressed
biologically, with high pre-morbid levels of oxidative stress, resulting
in high peroxynitrite levels.
Other biological stressors may be
the cause or add to this, such as IAG or these may be mechanical, dietary,
environmental, physical, infective or psychological.
What seems
important is that the blood-brain barrier becomes permeable allowing viral
entry. Treatments should be aimed at identifying and removing these
stressors This then could allow neurotropic viruses to cause the
hypothalamic and other downstream hormone effects. There also exists a
chronically activated immune system, which may result from the initial
insult or co-existent microbial, or toxin overload or a combination of the
two. It seems that there is over-expression of aberrant RNA, derived
initially from an enterovirus, protected by a viral type coat which in the
presence of LMWRNase L leads to extreme ATP depletion.
Does the
body feel that it is being constantly infected by an enterovirus?
Pollution and vaccines have been suggested as a cause for the loss of
control of HERV associated mRNA production. Following this
hypercoagulability develops, causing problems in both blood and lymph
microcirculation’ s. This hypercoagulability may arise from a combination
of hereditary, immune mediated and oxidative stress pathways. We have
chronic sympathetic system activation, from many causes.
We then
have a situation where the body is subject to a high degree of oxidative
stress, probably the most damaging state in biology. I feel Fibromyalgia
is mainly an illness of oxidative stress associated with spinal problems
as outlined above. Multiple subtle endocrine changes are also present in
the CFS/ME/FM complex, both quantitatively in terms of hormone levels, and
also qualitatively, with loss of circadian rhythmicity.
Given the
bi-directional flow of information between the nervous, endocrine and
immune systems, we are presented with a perfect example of Chaos Biology.
This results in a failure of homeostasis and homeodynamics. Simply stated,
a body that cannot respond to any form of biological stress, be it
environmental, infective, physical or psychological.
Although some
of the ideas I have presented are novel and controversial, I believe the
overall hypothesis has a sound base in science. We must remember that all
explanations for these groups of illnesses are at present speculative.
However, the studies demonstrating pathophysiology are not and neither are
the results of treatment programs.
I am afraid that as a
profession, it seems we have shot ourselves in the foot again, and have
assumed psychological causation, because of our lack of knowledge. Medical
history is littered with illnesses that were thought to be psychogenic,
e.g., Tuberculosis, epilepsy and Hypothyroidism. We need to act quickly to
repair the damage and work for funding for patients on the NHS.
©
2002 Dr. Andrew John Wright.
The preceding is an excerpt. To read this report in its
entirety, please visit: http://www.cfsresearch.org/cfs/research/treatment/36nf.htm
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