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Fibromyalgia -- A Physician's Guide David A. Nye MD, 14Dec96
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 2). On examination, areas of focal tenderness called
tender points can be demonstrated in characteristic locations
(table 3). Most patients can be helped substantially with
treatment.
Etiology
A comprehensive review of the many theories of the etiology of
FMS is beyond the scope of this paper. While there is still
not a majority of FMS researchers who support any one theory,
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 a
number of studies have established that FMS is neither a
psychosomatic nor somatiform disorder and that when present,
anxiety and depression are more likely to be the result than
the cause of FMS (Goldenberg 1989, Yunus 1991, Dunne 1995).
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, reports of
muscle biopsy abnormalities other than disuse atrophy have been
difficult to replicate (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). Muscle energy
metabolism is normal in FMS (Simms 1994, Vestergaard-Poulsen
1995).
FMS may be due to non-restorative deep sleep (Moldofsky 1975,
1993). Patients with FMS often report insomnia or light sleep
as well as an increase in FMS symptoms after disturbed sleep
(Campbell 1983). Abnormal amounts of alpha activity on the
electroencephalogram of FMS patients during deep sleep have
been reported (Hauri 1973, Moldofsky 1975). FMS-like symptoms
can be induced in normal volunteers by depriving them of deep
sleep, except in subjects who exercise regularly (Moldofsky
1975). Controlled 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 therapeutic effect.
A number of changes in immune system function have been found
in FMS, generally in the direction of increased activity, many
of which can also be induced in normal volunteers through sleep
deprivation (Moldofsky 1993). Many of the symptoms of FMS
may be caused by elevations, induced by abnormal sleep, in
certain cytokines such as interleukin-2, which has been found
to be elevated in FMS patients, and which causes FMS-like
symptoms when given intravenously (Wallace 1990, Moldofsky
1995).
Serotonin appears to be important in FMS. Serum levels of
serotonin and its dietary precursor tryptophan are low in FMS
(Russell 1996). Amitriptyline, one of the medications often
used to treat FMS (see below), blocks serotonin reuptake and
increases deep sleep (Baldessarini 1985). Serotonin is
important in deep sleep and in central and peripheral pain
mechanisms (Chase 1973).
The concentration of substance P, a peripheral pain neuro-
transmitter, is several times higher in the cerebrospinal fluid
of FMS patients than in pain-free controls, implying a
peripheral origin for FMS pain (Russell 1994). A number of
other neuroendocrine abnormalities have been identified in FMS
patients (Crofford 1994, Moldofsky 1995, Russell 1996) which
form the basis for other theories of the etiology of FMS.
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 such as trauma, infection, stress, or
sleep disruption. The immunologic abnormalities suggest an
infectious etiology, but if FMS were infectious we would expect
to see an increased incidence in spouses of an affected patient
and not just in their children and this is not the case.
Diagnosis
Since FMS is a syndromic diagnosis, any patient who fits the
diagnostic criteria of chronic, diffuse aching with tenderness
in at least 11 of 18 characteristic locations (Table 3) has it
by definition. It is not possible to accurately diagnose FMS
without knowing how to do a tender point examination. It
cannot be accurately diagnosed by exclusion. One would expect
medical students to have been taught in physical diagnosis how
to examine for a disorder that accounts for more than 5% of a
primary care practice but lamentably this is not yet the case
in most medical schools. If a patient has typical symptoms of
FMS (Table 2) but does not meet the tender point criterion, a
diagnosis of "possible FMS" may be assigned and a therapeutic
trial of standard treatment offered. Tender points should be
looked for again on a return visit as they may be more evident
on some days than others.
Although there have been many abnormalities of laboratory and
other tests reported in FMS, none is sufficiently sensitive nor
specific to be useful diagnostically, so routine studies are
not recommended. Patients who haven't recently had a general
medical evaluation should as part of the workup, and other
tests should be ordered when the history or exam raises a
question of something other than FMS. In older patients a
sedimentation rate may be useful to exclude polymyalgia
rheumatica. In patients with other symptoms of hypothyroidism,
thyroid studies may be 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 degree of pain. Some of these patients followed over time
will subsequently develop tender points and then fit the
criteria for diagnosis of FMS. 70% of patients with FMS meet
the CDC criteria for CFS (Buchwald 1987) and two thirds of
patients with CFS meet the ACR criteria for FMS (Goldenberg
1990b). It seems unlikely that these patients have two
separate disease processes. 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
Controlled studies have shown that amitriptyline (Goldenberg
1986, Jaeschke 1991), cyclobenzaprine (Quimby 1989), alprazolam
(Russell 1991), aerobic exercise (McCain 1988), and other
interventions to be discussed later are of benefit in treating
FMS, but the percentage of patients responding to each alone is
small. When gentle daily aerobic exercise, a consistent bed
time with adequate amounts of sleep, and one of several
medications to improve deep sleep are combined, as expected
more patients improve. This approach has not yet been studied
rigorously, but in a retrospective chart review I found that 30
of 36 patients (83%) had improved substantially with it, many
of those to the point of having no aching most of the time.
Trazodone, diphenhydramine, carisoprodol, and doxepin have
similar effects on deep sleep and are also widely prescribed
for sleep in FMS, but have not yet been studied in controlled
blinded trials. Cyclobenzaprine and diphenhydramine are
pregnancy category B and thus preferable in women who are or
are attempting to become pregnant. Alprazolam is pregnancy
category D and so should be avoided in these patients.
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 and increased
every few days to a week to maximum relief of daytime FMS
symptoms without unacceptable side effects. I allow patients
to fine-tune the dose themselves. The starting doses and
ranges of several medications useful in the treatment of FMS
are listed in Table 1 in roughly the order I tend to try them.
Amitriptyline is an effective medication for FMS but it has
frequent daytime side effects attributable to its long half
life such as weight gain, dry mouth, and cognitive impairment.
I usually start with shorter-acting medications which help
sleep and are gone during the day.
It is often necessary to try several different medications in
succession and sometimes in combination before finding a
regimen that works well. Some tolerance often develops to the
sedative effect of many of these, necessitating one or two dose
increases after an initial good response to maintain efficacy.
When switching from one medication to another, it is important
to taper the first slowly as the second is increased to try to
maintain sleep quality and avoid exacerbating FMS symptoms.
Imipramine, steroids, and non-steroidal anti-inflammatory drugs
(NSAIDs) have all been found to be no better than placebo
(Goldenberg 1993). While NSAIDs might be expected to be
helpful if only for the analgesic effect, their tendency to
cause some insomnia may cancel out the expected benefit.
Narcotics and benzodiazepines other than alprazolam block stage
4 sleep and so should be avoided. While they may help
symptomatically, they often make the patient feel worse the
next day and may prevent her from ever being able to get to the
point of being pain-free most of the time. Tramadol and
acetaminophen do not seem to interfere with sleep and are
therefore a better choice for analgesia.
Fluoxetine was found in one study to be ineffective except to
symptomatically treat associated depression (Wolfe, 1994). A
second study found it effective in combination with
amitriptyline (Goldenberg 1996), but this may have been because
fluoxetine increases amitriptyline levels which weren't
monitored. A second serotonin re-uptake inhibitor, citalopram,
was ineffective for FMS symptoms (Nxrregaard 1995).
There are many other unstudied "alternative" drug and herbal
treatments, some of which may in the future be proven effective
in controlled studies. I do not recommend these since they are
as yet unproven scientifically and may have unrecognized
toxicities, but I have given up trying to dissuade patients
from trying them as long as it is not in place of conventional
therapy.
Daily, gentle, low-impact aerobic exercise helps (McCain 1988),
but too much or the wrong kind of exercise may exacerbate FMS
symptoms. Patients who are deconditioned should start out with
just 3-5 minutes of exercise every day and increase as
tolerated, usually up to 20-30 minutes a day. The benefit of
the exercise seems to be from its systemic effects rather than
any direct effect on the exercised muscles. It works better if
the patient avoids exercising the most painful muscles.
Patients should try different ways of exercising to find the
best kind for them. Walking or bicycling outside or various
kinds of home exercise equipment are the most popular. Aerobic
water exercise may be best tolerated because it eliminates
weight-bearing, but it is hard for patients to get to a pool
every day. Water exercise can be useful to get patients
started when they can't tolerate anything else. Once their
stamina improves, they should add another form of exercise on
the days they don't swim. Exercise is most effective if done
in the late afternoon or early evening, perhaps because of its
known effect on deep sleep. A small percentage of patients can
never get up to an effective amount of exercise, but without
it, few will improve much in my experience. Patients who have
been exercising daily and then skip a day will usually complain
of feeling worse for 2-3 days afterward, an experience which
often helps convince them of the need for daily exercise.
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. I have not been able to get patients who
swing shifts to improve substantially unless they can get onto
shifts that allow them to sleep nights and keep a consistent
bedtime.
Other coexisting sleep disorders such as obstructive sleep
apnea (OSA) and periodic limb movements of sleep must be
identified and treated. Not infrequently a spouse's snoring
will exacerbate the patient's symptoms, in which case treating
the spouse's snoring or having the patient wear ear plugs will
help. 44% of men with FMS have been found to also have OSA
(May 1993), a potentially life-threatening disorder which is
important to treat in its own right. 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, referral to a sleep disorders center for
polysomnography may be helpful.
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 housework 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 smaller amount of time every
day at such activities until they are completed. Patients must
learn to sense when they have reached their limit and stop
before they get into trouble.
Other treatment modalities which have been shown in controlled
studies to be helpful include EMG biofeedback (Ferraccioli
1989), regional sympathetic blockade (Bengtsson 1988), and
cognitive behavioral therapy (Goldenberg 1991). Many patients
report that gentle massage as well as heat and rest help.
Some report that, as with migraine, certain foods appear to
precipitate their symptoms. Several patients have told 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 and other stimulants entirely. Alcohol should be
avoided because of its tendency to suppress deep sleep. This
is usually not a problem because most FMS patients tolerate
alcohol poorly to begin with. Certain symptoms such as
migraine headaches or depression can also be treated directly
if treatment of the underlying disorder does not control them
adequately.
FMS and myofascial pain syndrome (MPS), while probably 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. MPS
is usually treated with avoidance of activities which worsen
it, myofascial release and other forms of physical therapy, and
if necessary, trigger point injections or dry needling.
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 therapeutic 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 often takes two weeks or more 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.
A small number of patients continue to do poorly despite
treatment. Severely affected patients who can't be controlled
otherwise (treatment failures) need to be involved in a chronic
pain program, as outpatients or if necessary inpatients. Some
may need to apply for disability, which is harder to get for
patients with FMS because of the lack of supporting physical or
laboratory evidence, but guidelines are available (White 1995).
With treatment however, the majority who were working can
return to work although some may need to change jobs or get off
shift work. Most patients referred to me as treatment failures
had not had an adequate trial of treatment.
Conclusion
FMS is a common, chronic, and if untreated, often disabling
disorder of unknown etiology associated with neuroendocrine and
immunologic changes and disordered deep sleep. Most patients
can be helped with a combination of medication, exercise, and
maintenance 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. The common misconceptions that FMS is a
psychosomatic or somatoform disorder, is untreatable, is a
diagnosis of exclusion or a "wastebasket" diagnosis, and that
most FMS patients are hypochondriacs or whiners are unfounded.
Table 1: Some drugs useful in the treatment of FMS
Drug name Starting Taken __ hrs Usual maximum
dose (mgs) before bed dose (mgs)
trazodone 50 0 600
cyclobenzaprine 10 1 60
alprazolam 0.5 .5-1 6
carisoprodol 350 0-.5 1400
diphenhydramine 50 .5-1 300
5-hydroxytryptophan 100 1 600
amitriptyline 5 2 300
Table 2: 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 35.8
prior depression 31.5
irritable bowel syndrome 29.6
urinary urgency 26.3
Raynaud's phenomenon 16.7
Other commonly reported symptoms include dizziness, trouble
with memory and concentration, rashes, and chronic itching
(unpublished observations).
Table 3: Location of tender points (Wolfe 1990).
suboccipital muscle insertions at occiput
lower cervical paraspinals
trapezius at midpoint of the upper border
supraspinatus at its origin above medial scapular spine
2nd costochondral junction
2 cm distal to lateral epicondyle in forearm
upper outer quadrant of buttock
greater trochanter
knee just proximal to the medial joint line
To meet ACR 1990 diagnostic criteria for fibromyalgia, digital
palpation with an approximate force of 4 kgs. must produce a
report of pain in at least 11 of these 18 tender points. Other
areas can be tender as well. The tenderness should be focal
rather than diffuse. Tender points must be present on both
sides of the body, above and below the waist and in the midline.
Widespread pain must have been present for at least 3 months.
Some accept a diagnosis of fibromyalgia with fewer than 11
tender points if several associated symptoms from table 2 are
also present (Wolfe 1989).
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