From: mrl@nerus.pfc.mit.edu
Subject: Fibromyalgia article.
Organization: MIT PLASMA FUSION CENTER
Date: Wed, 30 Dec 1992 01:21:40 GMT

From: "David A. Nye MD" <NYEDA@cnsvax.uwec.edu>
Subject: Fibromyalgia article

Here's an article I wrote for a PR glossy our department puts out:

        Fibromyalgia                                    David A. Nye, MD


        Fibromyalgia is a common, underdiagnosed disorder affecting over
        5% of the patients in a general medical practice (Campbell
        1983).  It is often disabling but easily treated.  It affects
        women more often than men, with an age of onset ranging from 12
        to 45 years.  Patients complain of chronic diffuse aching,
        fatigue, morning stiffness, sleep disturbance, paresthesias,
        headaches, and a number of other symptoms (table 1).  On
        examination, areas of focal tenderness called tender points can
        be demonstrated in characteristic locations (table 2).

        Fibromyalgia was originally described by Gowers in 1904 as an
        inflammatory condition (Gowers 1904).  When no evidence for an
        inflammatory or degenerative process could be found and an
        association was noted with depression and stress, the concept of
        "psychogenic rheumatism" was advanced (Boland 1947).  Since the
        incidence of depression and other psychiatric disorders in
        fibromyalgia has subsequently been shown to be no greater than
        in other chronic, painful, debilitating conditions (Goldenberg
        1989), it is no longer felt that fibromyalgia is a psychosomatic
        or somatiform disorder, although both depression and anxiety may
        contribute to the onset of symptoms through sleep disruption.

        Patients with fibromyalgia often report subjectively shallow
        sleep as well as an increase in fibromyalgia symptoms after
        disturbed sleep (Campbell 1983).  In 1973, Hauri and Hawkins
        reported abnormal amounts of electroencephalographic alpha
        activity during deep sleep in patients with symptoms of
        fibromyalgia (Hauri 1973).  Moldofsky et al. reproduced these
        findings and were able to induce fibromyalgia symptoms in normal
        volunteers by depriving them of deep sleep (Moldofsky 1975).
        They noted however that sleep deprivation did not induce
        symptoms of fibromyalgia in subjects who exercised.  Subsequent
        trials have confirmed the value of aerobic exercise in the
        treatment of fibromyalgia (McCain 1988).  Exercise increases
        time spent in deep sleep (Hobson 1968), perhaps the the
        mechanism for its theraputic efficacy.

        Others have suggested that the pain of fibromyalgia is related
        to microtrauma in deconditioned muscles and that exercise works
        by conditioning these muscles (Bennett 1989).  However, it has
        been pointed out (Smythe 1989) that some tender points are not
        over muscles or tendons, such as the one over the medial fat pad
        of the knee, making it unlikely that muscle anoxia or
        microtrauma cause the pain of fibromyalgia.  I have observed
        that patients do better if they exercise mainly uninvolved
        muscles and get their exercise in the evening rather than in the
        morning, evidence that exercise helps through its effect on
        sleep rather than through any direct effects on sore muscles.
        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).

        Moldofsky et al. speculated that fibromyalgia may be related to
        abnormal and non-restorative deep sleep, perhaps due to
        abnormalities of serotonin metabolism (Moldofsky 1975).
        Serotonin is important in deep sleep and central and peripheral
        pain mechanisms (Chase 1973).  Amitriptyline, the most useful
        medication for treating fibromyalgia, blocks serotonin reuptake
        and increases deep sleep (Baldessarini 1985).  Other studies
        have suggested the possible involvement of substance P (Vaeroy
        1988) and catecholamines (Russell 1986) in fibromyalgia.  The
        etiologic significance of these findings is not clear, since in
        another study patients with fibromyalgia were shown to have a
        neurotransmitter plasma profile similar to those in other
        chronic pain states (Hamaty 1989).

        The presence of considerable symptom overlap in fibromyalgia,
        chronic fatigue syndrome, and irritable bowel syndrome and the
        efficacy in all of low doses of amitriptyline has led to
        speculation that they may be different facets of the same
        underlying, as yet unknown disease process, possibly a viral
        infection (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).

        Most patients with fibromyalgia respond favorably to low doses of
        amitriptyline, vigorous exercise, and maintenence of a regular
        schedule of adequate amounts of sleep.  On this regimen, 30
        (83%) of the last 36 patients I have seen with fibromyalgia have
        had substantial improvement.

        Amitriptyline is more effective than antiinflamatory medications
        or other anti-depressants in the treatment of fibromyalgia, and
        appears to work through its effect on deep sleep (Goldenberg
        1986).  It should be started at 5 mgs. an hour or so before
        bedtime.  The dose should be increased by 5-10 mgs. every 4-7
        days to maximum relief of symptoms without unacceptable side
        effects.  In the 30 patients mentioned above, the best dose
        ranged from 2.5 to 300 mgs. per day but generally was between 30
        and 60 mgs. per day.  The few patients who experience an initial
        stimulant effect and tachycardia from amitriptyline should take
        it earlier in the evening so that this effect has given way to
        sedation by the patient's usual bedtime.  The dose usually needs
        to be pushed to the point that it causes a significant and
        continuous dry mouth.  When dry mouth and constipation are
        sufficiently bothersome, pyridostigmine may be used to block
        these and other peripheral anticholinergic side effects.  A
        craving for sweets is a common side effect of amitriptyline so I
        recommend that patients taking amitriptyline avoid sweets
        entirely to avoid weight gain.

        Daily, vigorous, low-impact aerobic exercise has also been shown
        to have a beneficial effect on fibromyalgia symptoms (McCain
        1988).  It appears to be more effective if done later in the
        day.  The kind of exercise does not seem to matter as long as it
        gets the heart rate into the aerobic range.  Aerobic dance
        videotapes can be used at home at a convenient time every day,
        are paced, and provide warm-up exercises that can help prevent
        injury.  The patient should choose a type of exercise that does
        not aggrevate their pain.  If the pain is worst in the back and
        legs, for example, exercise just the arms.

        Getting adequate sleep is essential.  Fibromyalgia symptoms
        commonly appear during times of sleep disruption (12) such as
        may be brought on by stress, pain, starting 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.

        Education, frequent follow-up visits, temporary dose reductions,
        and reassurance help to get patients over the initial side
        effects of amitriptyline, the most bothersome of which are
        usually fatigue and dizziness.  It may be difficult to convince
        patients to get adequate exercise because of their fatigue and
        because it may initially increase the aching.  It may take two
        weeks or so before the beneficial effects of the amitriptyline
        and exercise outweigh their side effects.  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"
        and tries to get extra rest during a relapse.

        In summary, fibromyalgia is a common, chronic, often disabling
        disorder of unknown etiology associated with disordered deep
        sleep and probably abnormalities involving serotonin or other
        neurotransmitters.  Most patients can be helped with a
        combination of amitriptyline, exercise, and maintenence of a
        regular sleep schedule.  Think of this condition in any patient
        with a complaint of aching 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                          35.8
            prior depression                        31.5
            irritable bowel syndrome                29.6
            urinary urgency                         26.3
            Raynaud's phenomenon                    16.7

        Other commonly reported associated symptoms include dizziness
        (often with some swaying on Romberg testing), an eczematous
        malar rash and chronic itching (my unpublished observations).


        Table 2: 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 (bilateral) tender
        points.  Other areas can be tender but the tenderness should be
        focal rather than diffuse.  In addition, 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).


        References:

        Baldessarini RJ.  Drugs and treatment of psychiatric disorders.
            In: LS Goodman and A Gilman eds., The pharmacologic basis of
            theraputics.  7th ed., New York: MacMillan, p. 413, 1985.

        Bennett RM.  Beyond fibromyalgia:  ideas on etiology and
            treatment.  J Rheumatol (suppl 19) 16:185, 1989.

        Boland EW.  Psychogenic rheumatism: the musculoskeletal
            expression of psychoneurosis.  Ann Rheum Dis 6:195, 1947.

        Campbell SM et al.  Clinical characteristics of fibrositis.
            I. A "blinded" controlled study of symptoms and tender
            points. Arthritis Rheum 26:817-24, 1983.

        Chase TN and DL Murphy.  Serotonin and central nervous system
            function.  Ann Rev Pharmacol 13:181, 1973.

        Gowers WR.  Lumbago -- its lessons and analogues.  Br Med J.
            1:117, 1904.

        Goldenberg DL et al.  A randomized controlled trial of
            amitriptyline and naproxen in the treatment of patients with
            fibromyalgia.  Arthritis Rheum 29:1371, 1986.

        Goldenberg DL.  Psychological symptoms and psychiatric diagnosis
            in patients with fibromyalgia.  J Rheumatol (suppl 19)
            16:127, 1989.

        Goldenberg DL.  Fibromyalgia and chronic fatigue syndrome:
            are they the same?  J Musculoskel Med. 1990;7:19-28.

        Hamaty D et al.  The plasma endorphin, prostaglandin and
            catecholamine profile of patients with fibrositis treated
            with cyclobenzaprine and placebo:  a 5-month study.  J
            Rheumatol (suppl 19) 16: 164, 1989.

        Hauri P, Hawkins DR.  Alpha-delta sleep.  Electroenceph Clin
            Neurophysiol. 34:233, 1973.

        Hobson JA. Sleep after exercise.  Science 162:1503, 1968.

        McCain GA et al.  A controlled study of the effects of a
            supervised cardiovascular fitness training program on
            manifestations of primary fibromyalgia.  Arthritis Rheum
            31:1135, 1988.

        Moldofsky HD et al.  Musculoskeletal symptoms and non-REM
            sleep disturbance in patients with "fibrositis syndrome" and
            healthy subjects.  Psychosom Med. 1975;37:341-351.

        Pellegrino MJ et al.  Familial occurrence of primary
            fibromyalgia.  Arch Phys Med Rehab 70:61, 1989.

        Smythe H.  Fibrositis syndrome: a historical perspective.  J
            Rheumatol (suppl 19) 16:2, 1989.

        Wolfe F.  Fibromyalgia:  the clinical syndrome.  Rheum Dis Clin
            North Am. 15:1, 1989.

        Wolfe F et al.  The American College of Rheumatology 1990
            criteria for the classification of fibromyalgia: report of
            the multicenter criteria committee.  Arthritis Rheum.
            33:160, 1990.

        Yunus MB et al.  A controlled study of primary fibromyalgia
            syndrome: clinical features and association with other
            functional syndromes.  J Rheumatol 1989;(suppl 19)16:62-71.

Mark London
MRL@NERUS.PFC.MIT.EDU