FIBROMYALGIA

David A. Nye, M.D.
Midelfort Clinic

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 anti-inflamatory 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 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.


ADDENDUM

Fibromyalgia is a common and disabling disorder affecting one in 20 people, women more often than men. Despite the condition's frequency, the diagnosis is often missed. Patients with fibromyalgia usually ache all over, sleep poorly, are stiff on waking and feel tired all day. They are prone to headaches, dizziness, numbness and tingling, itching, facial rashes, fluid retention, crampy diarrhea and other symptoms. Fibromyalgia may be closely related to the chronic fatigue and irritable bowel syndromes. There are no reliable lab or x-ray abnormalities, but a physician can confirm the diagnosis by finding multiple tender points in characteristic locations.

Fibromyalgia was originally thought to be a form of joint, muscle or tendon inflammation, but no evidence of inflammation or arthritis could be found. When it was noted to worsen with depression and stress, it was thought perhaps to be a psychiatric disorder. Many patients are still told that their symptoms are stress-related, but this appears not to be the true. Patients with fibromyalgia have been found to be no more depressed than patients with other chronic, painful, debilitating conditions. It is now believed to be due to an imbalance of chemicals in the brain associated with malfunctioning deep sleep. Abnormal brain waveforms have been found in deep sleep in some patients with fibromyalgia. The symptoms of fibromyalgia can be produced in normal volunteers by preventing them from getting any deep sleep for a few days.

The cause of fibromyalgia is unknown, but a predisposition to it may be inherited. It often runs in families. It may lie dormant until something happens to disrupt sleep, such as increased stress, pain, swinging shifts, or having to get up with children. Sometimes just getting regular, adequate sleep again is enough to make the symptoms disappear. Usually however, additional treatment is needed.

Amitriptyline (Elavil), a medication commonly used to treat depression, also helps fibromyalgia. It probably works by improving the quality and depth of deep sleep rather than by any effect on mood. When sleep is normalized, all of the other associated symptoms of fibromyalgia begin to improve. Patients taking amitriptyline usually don't note significant improvement until they are on enough to make them sleep through the night.

Amitriptyline frequently produces mild side effects. An increase in sleepiness or dizziness should be expected when it is first taken. Starting at a low dose taken an hour or more before bedtime and increasing gradually helps minimize these initial side effects. Those patients who notice an initial stimulant effect of amitriptyline, perhaps with a rapid heartbeat, should take it earlier in the evening, so that this effect has given way to sedation by bedtime. By the end of two weeks, most patients are noticing that the side effects are settling down and the medication is beginning to help their fibromyalgia symptoms.

Almost everyone on enough amitriptyline to help fibromyalgia gets a dry mouth and often some constipation. If these side effects are severe, another medication called Mestinon can be added to block them, generally with no other side effects of its own. Amitriptyline may cause a craving for sweets, although usually not for calories in other forms. I recommend you avoid sweets entirely while on amitriptyline to avoid weight gain.

Daily, vigorous exercise is also important in the treatment of fibromyalgia. Exercise is more effective if done in the evening. Fifteen to thirty minutes of exercise is usually sufficient. The exercise seems not to work through conditioning of muscles but rather through a direct, possibly hormonal effect on sleep. Patients who have been exercising regularly and then miss a day usually find that their fibromyalgia symptoms are significantly worse the next day.

The kind of exercise is unimportant as long as it is vigorous. Just make sure to pick something that doesn't increase your pain. The exercise should get your heart rate up and and make you get a little short of breath. Less than vigorous exercise provides no benefit and may actually make you feel worse. Be sure to warm up adequately with some stretches before starting to exercise to avoid injury.

It is important to maintain a regular schedule of sufficient sleep. Avoid caffeine and alcohol in the evenings, both of which may disrupt sleep. Try not to exercise just before bed, as this may make it harder to fall asleep.

Even with good results from treatment, brief relapses are common, often caused by temporary sleep disturbances, such as staying up as little as one hour late one evening, or skipping exercise. You will do best if you "give in to it" when this happens and try to get extra rest.

Feel free to call us here at the office if problems develop, particularly if you are having significant problems with medication side effects.

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