NOTE: This message was originally in conference "INTERNET - E-MAIL AREA"
      and was copied here by Tom Mckeever.
From: tomincal@JUNO.COM
To: Multiple recipients of list POLIO 
Date:         Sun, 6 Oct 1996 03:29:37 EDT
Subject:      More on Fibromyalgia Syndrome
 
Forwarded by: tomincal@juno.com
---------
A Physician's Guide to Fibromyalgia Syndrome
David A. Nye MD, Neurology, Midelfort Clinic, Eau Claire WI
 
Fibromyalgia syndrome (FMS) is an underdiagnosed disorder of
unknown etiology affecting over 5% of the patients in a general
medical practice (Campbell 1983) and an estimated 2-4% of the
general population (Wolfe 1993), women more often than men. Patients
complain that they ache all over. A large number of other symptoms are
often present, particularly fatigue, morning stiffness, sleep
disturbance, paresthesias, and headaches (see table 1). On examination,
areas of focal tenderness called tender points can be demonstrated in
characteristic locations (table 2).
 
Etiology
There are many theories regarding the etiology of FMS, only a
few of which I will discuss here.  At this point there does not appear to
be a majority of FMS researchers supporting any single theory.  While it
still must be said that the etiology is unknown, significant progress is
being made in identifying an etiology, and much useful evidence has been
collected.
 
FMS was first described as an inflammatory condition (Gowers
1904). When no evidence of inflammation could be found and an
association was noted with depression and stress, the concept of
"psychogenic rheumatism" was advanced (Boland 1947), but the
incidence of depression and other psychiatric disorders in FMS
has since been shown to be no greater than in other chronic,
painful, debilitating conditions (Goldenberg 1989). While it is
believed that depression and anxiety may contribute to the onset
of symptoms through sleep disruption, FMS is no longer felt to be a
psychosomatic or somatiform disorder.
 
It has been suggested that the pain of FMS is related to microtrauma in
deconditioned muscles and that exercise works by conditioning these
muscles (Bennett 1989). However, muscle biopsy has tended to show only
changes of disuse atrophy (Schroder 1993), and some tender points are not
over muscles or  tendons, such as the one over the medial fat pad of the
knee (Smythe 1989). Furthermore, exercise seems to work best if it mainly
uses less-involved muscles published observations).
 
Moldofsky has suggested that FMS may be due to non-restorative
deep sleep (Moldofsky 1975, 1993). Amitriptyline (Elavil), the most
commonly used medication for treating FMS, blocks serotonin
reuptake and increases deep sleep (Baldessarini 1985). Serotonin is
important in deep sleep and in central and peripheral pain mechanisms
(Chase 1973). A number of other  neurotransmitter, neuroendocrine, and
immunologic abnormalities have been identified in FMS patients, none with
sufficient sensitivity and specificity to be diagnostically useful, but
they have formed the basis for several other theories of the etiology of
FMS. A cataloging of all of them is beyond the scope of this review.
Moldofsky points out that many of these
changes can be induced simply through sleep deprivation (Moldofsky 1993).
 
Patients with FMS often report insomnia or light sleep as well as an
increase in FMS symptoms after disturbed sleep (Campbell 1983).  Hauri
and Hawkins reported abnormal amounts of alpha activity on the
electroencephalogram of FMS patients during deep sleep (Hauri 1973).
Moldofsky et al. were able to induce FMS-like symptoms in normal
volunteers by depriving them of deep sleep, except in subjects who
exercised regularly (Moldofsky 1975). Subsequent trials have confirmed
the value of aerobic exercise in the treatment of FMS (McCain 1988).
Exercise increases time spent in deep sleep (Hobson 1968), perhaps the
mechanism for its theraputic efficacy. Deep sleep serves an important
physical restorative function, probably modulated by somatostatin, which
is released almost exclusively during stage
4 sleep in amounts that increase after exercise (Bennett 1989).
Patients with FMS have been shown to have low somatostatin levels
(Bennett 1991).
 
The presence of considerable symptom overlap in FMS, chronic
fatigue syndrome, and irritable bowel syndrome and the efficacy
in all of low doses of amitriptyline has led to speculation that
they may represent different facets of the same underlying, as yet
unknown disease process (Goldenberg 1990, Yunus 1989). Although no
specific inheritance pattern has been identified, an increased incidence
in relatives of affected patients has been noted (Pellegrino 1989).
Development of the syndrome may require a predisposing factor, possibly
inherited, as well as a precipitating factor, perhaps something
disturbing sleep.
 
Diagnosis
Since FMS is a syndromic diagnosis, any patient who fits the diagnostic
criteria of aching all over and the presence of at least 11 of 18 tender
points (Table 2) has it by definition. It is not a diagnosis of
exclusion. The more associated symptoms from the list in Table 1 that are
present, the more secure the diagnosis. Tender points may be present some
days and not others. If a patient has a typical history of FMS but
doesn't meet the tender point criterion, tender points should be looked
for again on a return visit. Patients whom the physician
suspects have FMS but who fail to meet diagnostic criteria may be
classified as "possible FMS" and offered a theraputic trial of standard
treatment.
 
Although there have been many abnormalities of laboratory and
other tests reported in FMS, none is sufficiently sensitive or specific
to be useful diagnostically. Therefore, routine laboratory or other
studies are not recommended. Because the list of possible symptoms is
large in FMS, the differential diagnosis is also very large. Patients
with FMS should have a comprehensive medical evaluation as part of the
workup. In older patients a sedimentation rate is useful to exclude
polymyalgia rheumatica. In patients with other symptoms of
hypothyroidism, thyroid studies are indicated.
 
The current syndrome definition may not be the best one possible
(Wolfe 1993). It has been argued that tender points have been
over-emphasized, probably because historically rheumatologists
have been more involved in the diagnosis and treatment of FMS
than other specialists. In many patients who meet the criteria for
diagnosis for chronic fatigue syndrome, the only difference
between them and a typical FMS patient is the relative absence of pain.
Some of these patients followed over time will subsequently develop
tender points and then fit the criteria for diagnosis of FMS.  Perhaps
dividing these two groups of patients on the basis of whether or not they
have prominent pain is as artificial as division on the basis of
prominence of any of the other twenty or so associated symptoms.
 
On the other hand, we are to some extent stuck with the current
syndrome definition because it is these patients on whom all the
important studies have been performed. If the syndrome definition is
altered, we can't be certain that all of these results still apply to the
new syndrome. This problem will disappear once we know the true etiology
and can make an etiologic rather than syndromic diagnosis.
 
Treatment
Most patients with FMS respond favorably to gentle aerobic exercise,
maintenence of a regular schedule of adequate amounts
of sleep, and low doses of amitriptyline or other medications known to
improve deep sleep. On this regimen, 30 of 36 patients (83%) had
substantial improvement (unpublished observations). Several other
medications have been shown in controlled studies to help, including
cyclobenzaprine (Flexeril) (Quimby 1989) and alprazolam (Xanax) (Russell
1991). Diphenhydramine seems to be useful as well, although I am not
aware that it has been studied.
 
Imipramine, steroids, and non-steroidal anti-inflammatory drugs
(NSAIDs) are among those which were found to be no more
effective than placebo, although NSAIDs may be useful for simple
analgesia (Goldenberg 1993). Benzodiazepines other than alprazolam are
contraindicated as they block stage 4 sleep and may exacerbate FMS. The
serotonin-specific reuptake inhibitors such as fluoxetine (Prozac) have
not been very effective, consistent with the theory that the main
mechanism of action of medications effective for FMS is to promote deep
sleep.
 
There are many other unstudied drug and herbal treatments, some
of which would quite likely be proven effective in controlled studies. I
hesitate to recommend these myself since they are as yet unproven
scientifically, but I don't try to dissuade patients from trying them if
they want as long as it is not in place of conventional therapy.
 
Medications effective in the treatment of FMS appear to work
mainly through an effect on deep sleep (Goldenberg 1986). They
should be started at the lowest possible dose, such as half of a 10 mg.
tablet of amitriptyline, taken an hour or two before bedtime, then
increased every few days to a week to maximum relief of symptoms without
unacceptable side effects. The optimal dose of amitriptyline may be as
little as 2.5 mgs. or as much as 300 mgs., with an average between 30 and
60 mgs. (unpublished observations).
 
Amitriptyline is probably the most effective medication for FMS but it
also has the most side effects. If dry mouth or constipation are
sufficiently troublesome, pyridostigmine (Mestinon) can be added to block
these and other peripheral anticholinergic side effects. Weight gain is
another common side effect. I recommend that patients taking
amitriptyline avoid sweets entirely to avoid weight gain. Some patients
report that chromium supplements help reduce the craving for sweets. It
may be necessary to change to another medication
such as cyclobenzaprine or diphenhydramine which doesn't have
this side effect or use one of these in combination with a lower dose of
amitriptyline.
 
Daily, gentle, low-impact aerobic exercise helps FMS symptoms
(McCain 1988), but too much or the wrong kind of exercise may
exacerbate symptoms. Patients who are deconditioned should start out with
just 5 minutes of exercise every day and increase as tolerated. Most
patients need to be getting 20-30 minutes of exercise a day before they
will notice substantial benefit. The kind of exercise does not matter as
long as it gets the heart rate into the aerobic range and does not
aggrevate the patient's pain. If the pain is worst in the back and legs,
for example, the patient should exercise just the arms. Some patients may
need to try several different forms of exercise before they find one they
can tolerate. A small percentage of patients can never get up to an
effective amount of exercise, but without it, few
patients will notice much improvement. Exercise is most effective if done
in the late afternoon or early evening.
 
Getting adequate sleep is essential. FMS symptoms often appear
during times of sleep disruption (Saskin 1986) such as may be
brought on by an injury or other pain, stress, shift work, or having to
get up to attend to young children. At times just re-establishing a
regular sleep schedule may be enough to relieve symptoms. Patients must
also be careful not to overdo physical activity. For example, once she is
feeling better a FMS patient may try to catch up on all the cleaning she
has been unable to do, but this may trigger a relapse that puts her in
bed for several days. It is better to plan to spend a half an
hour or an hour a day at these activities until they are completed.
 
Other coexisting sleep disorders such as obstructive sleep apnea
(OSA) and periodic limb movements of sleep must be identified and
treated. 44% of men with FMS have been found to have coexistent OSA (May
1993). Not infrequently a spouse's snoring will significantly exacerbate
the patient's symptoms. It is important to take a sleep history in all
patients with FMS, including asking the spouse about snoring, apneas, and
movements at night. In resistant FMS cases, polysomnography may be
helpful.
 
Other treatment modalities which have been shown in controlled
studies to be helpful include EMG biofeedback (Ferraccioli),
regional sympathetic blocade (Bengtsson), and cognitive behavioral
therapy (Goldenberg). Many patients report that gentle massage as well as
heat and rest help. Others find that, as with migraine, certain foods can
precipitate their symptoms. Several patients have reported to me that
their FMS symptoms improved significantly on a low-fat weight reduction
diet started to lose the weight gained from taking amitriptyline. Most
patients do better if they give up caffeine entirely.
Alcohol tends not to be a problem as few patients with FMS seem
to be able to tolerate it well, but it should be avoided because of it's
tendency to suppress deep sleep. Certain symptoms can be treated directly
if treatment of the underlying disorder does not completely eradicate
them, for example migraine headaches or depression.
 
FMS and myofascial pain syndrome (MPS), while separate entities,
often coexist (Granges 1993). When they do each needs to be treated
separately. MPS is associated with trigger points which should be
distinguished from the tender points of FMS. Trigger points are located
over a band of taut muscle and cause pain that radiates away from the
point of pressure.
 
Support and education are important. Patients need to be actively
involved in their treatment and to have as clear an understanding of this
complicated disorder as possible. Patients often elicit less sympathy and
support from family, friends, and employers than they deserve because of
the lack of physical stigmata of disease. By the time they get to see
someone skilled in the management of FMS, many patients will have been
told by at least one other physician that there is nothing wrong with
them or that it is "all in your head" which
can be quite demoralizing. An understanding approach by the physician and
the patient's participation in a well-run support group may have
considerable theraputic benefit.
 
Education, frequent follow-up visits, and reassurance help to get
patients over the first few weeks of treatment. It may be difficult to
convince patients to exercise when they experience fatigue and aching. It
may take two weeks or so before the beneficial effects of medication and
exercise outweigh their side effects. Sometimes it takes several months
of trying different medications in different combinations and adjusting
doses before getting it right. The physician should check on the amount
and type of exercise and sleep at return visits and reinforce their
importance. Patients should be warned that despite optimum treatment and
good initial results, brief
relapses are common, often caused by temporary sleep disturbances. The
patient will do best if she "gives in to it", takes hot baths, and tries
to get extra rest during a relapse. A temporary increase in medication
dose may also be necessary.
 
Conclusion
FMS is a common, chronic, often disabling disorder of unknown
etiology associated with disordered deep sleep.  Most patients can
be helped with a combination of medication, exercise, and maintenence of
a regular sleep schedule. Think of this condition in any patient with a
complaint of aching and tiredness and look for associated symptoms and
tender points to confirm the diagnosis.
 
Table 1: Associated signs and symptoms (Wolfe 1990).
widespread pain                         97.6% of patients
tenderness in > 11/18 tender points     90.1
fatigue                                 81.4
morning stiffness                       77.0
sleep disturbance                       74.6
paresthesias                            62.8
headache                                52.8
anxiety                                 47.8
dysmenorrhea history                    40.6
sicca symptoms                     
--- WILDMAIL!/WC v4.12 
1:374/22.0)
---------------