Fibromyalgia is a common disorder associated with generalized pain. The etiology is not well understood, although consistent derangements in normal physiology are well described and may contribute to patients' symptoms. This article reviews briefly the pathophysiology and treatment options and describes a management approach to these patients.

Understanding and managing chronic pain is a major challenge for clinicians in their everyday practice. Chronic generalized pain is a common finding in the population, being reported by approximately 13 per cent of people in one UK postal survey.1

Although most clinicians are familiar with, and have developed skills to manage regional pain syndromes such as low back pain, they are often less confident in their ability to deal with generalized chronic pain.

Fibromyalgia is a chronic pain syndrome with an associated constellation of symptoms including non-restorative sleep, fatigue, mood alterations, stiffness and non-neurological parasthesia. It is often associated with other conditions, such as chronic fatigue and irritable bowel syndromes.

Approximately two per cent of the population are affected, and fibromyalgia predominantly affects women (the female:male ratio is up to 9:1). Fibromyalgia is increasingly common with age: it can be found in eight per cent of women in their seventies.

In the USA it is the second most common condition managed by rheumatologists.

Fibromyalgia can co-exist with other conditions, including other rheumatological disorders, and up to 30 per cent of patients with rheumatoid arthritis are also diagnosed with fibromyalgia.2

* Etiology

The cause of fibromyalgia remains unclear and many different possibilities have been suggested. These include alterations in normal sleep, altered central nociceptive and neuroendocrine responses, and psychological problems.2,5

Although many disturbances of normal physiology have been described, it remains unclear why particular individuals develop these responses, what triggers them and, indeed, whether they are primary or secondary phenomena.

Fatigue and non-restorative sleep are common symptoms and seem to result from a reduction in non-REM sleep. Whether this is cause or effect has been (and remains) a matter of considerable debate, but disruption of non-REM sleep in normal volunteers has been associated with inducing symptoms with similarities to fibromyalgia, including stiffness, muscle aching and tender points.

The experience of pain is a complex phenomenon resulting from interplay between noxious stimuli, emotional traits and cognitive factors. Many clinicians mistakenly view pain as a consistent phenomenon in which a stimulus will always produce the same response. In fact, like many other neurological processes, the experience of pain is plastic and chronic pain can induce central changes that favour continuance of pain despite removal of the apparent cause. This is termed non-nociceptive pain and is involved in conditions like trigeminal neuralgia or reflex sympathetic dystrophy.

Altered pain responses can be experimentally demonstrated in patients with fibromyalgia. These patients exhibit hyperalgesic responses to painful stimuli, but also have pain responses to non- painful stimuli such as pressure (allodynia). Augmented responses to heat, cold and auditory stimuli have also been seen.

Using sophisticated imaging techniques, alterations in blood flow have been seen in the thalamic and caudate nuclei of patients with fibromyalgia. These centres are involved in processing painful stimuli and such changes are also seen in other chronic pain states.

A number of abnormalities of central neuroendocrine function have also been described. They include high CSF levels of substance P, which may have a major role in central pain modulation. Low CSF levels of serotonin, tryptophan and IGF1 have been reported in some patients, along with abnormalities of the hypothalamic-pituitary axis. These changes are probably secondary phenomena and link into affective problems encountered in these patients.

In common with most chronic conditions, patients with fibromyalgia have an increased prevalence of major depression and have higher levels of psychological distress than healthy individuals. Those with higher scores on indices of psychological distress are more likely to seek medical attention than those who do not.

* Investigations

The characteristic of fibromyalgia is the absence of abnormalities on other investigations. It is our practice to carry out a range of simple tests to exclude other conditions, and to reassure patients that their condition is being taken seriously (see table 1).

In general, radiological investigations show nothing specific to the condition and degenerative changes, which are common with increasing age, are usually not the cause of the patient's symptoms.

* Drug therapy Clinical trials of drug therapy for fibromyalgic symptoms have often produced disappointing results.2,6 Most of these studies are of short duration and have been based in centres with a particular interest in fibromyalgia, which may have introduced a selection bias because patients attending specialist centres may have more pronounced symptoms, may have symptoms of longer duration or may have adopted illness behaviours that differentiate them from the average patient.

The results of clinical trials may not therefore accurately represent the majority of patients with fibromyalgia. For example, surveys of self-reported benefit have suggested that simple analgesics may be effective for many patients, although clinical trials of non-steroidal anti-inflammatory drugs have produced no evidence of benefit.

Amitriptyline has been the most consistently effective drug studied in clinical trials. Beneficial effects, particularly on fatigue, are seen in one-third of patients. These are usually present within weeks, but there is evidence that effects plateau and may wane over a period of one year. Many trials have used a `start low and go slow' policy, beginning with doses of amitriptyline as low as 10mg and increasing gradually to 50mg. This approach is important as it may avoid some anticholinergic side-effects of the drug, to which fibromyalgic patients seem to be particularly sensitive.

Selective serotonin reuptake inhibitors have not been particularly effective, but have had some beneficial effects on sleep and indices of depression.

One study, which examined the effect of either fluoxetine, amitriptyline or the combination, suggested that combination therapy was more effective than monotherapy. Venlafaxine, a non-selective serotonin reuptake inhibitor, has some beneficial effects, but to date this has not been rigorously studied.

Although non-steroidal anti-inflammatory drugs and simple analgesics are widely used, they have not been shown to be effective in clinical trials. A similar statement can be made about corticosteroid treatment and magnesium supplementation. One small study, which examined the long-term effects of growth hormone replacement in women who had low levels of IGF1 in the absence of pituitary disease, suggested that it was beneficial; however, the cost of such therapy is prohibitive.

* Other therapies

Not unexpectedly in a condition in which drug therapy has disappointing effects, a wide range of other treatments have been employed. Many patients with this condition also attend alternative or complementary practitioners whose interventions have not been formally studied. Methods that have been formally assessed include cognitive therapies and stress management, exercise, education, biofeedback, acupuncture and hypnosis.

Outcomes in fibromyalgia are adversely effected by maladaptive coping strategies or the development of a catastrophic world view. Cognitive behaviour therapies (CBT) have shown to be beneficial in a number of studies, although the picture is somewhat confused since they often took place in collaboration with other activities such as exercise and education.

There is evidence to suggest that beneficial effects of CBT are more likely to be seen in those with a shorter duration of illness, perhaps because there has been less opportunity to develop maladaptive illness behaviours. Importantly, there is some evidence that, unlike most other therapies, the effects of CBT are long- lasting.

Many patients with fibromyalgia become physically unfit because they limit their physical activity. Several studies have examined whether physical conditioning improves outcomes; they have generally found that patients benefit from such interventions, but there is evidence that the effects do not persist beyond the duration of study.

This probably reflects adoption of previous patterns of activity outside the confines of the clinical trial. A small amount of evidence is available for the use of biofeedback, acupuncture and hypnosis, suggesting that these approaches may be of use in some patients.

* Course

Outcome data suggests that many patients, particularly those who are mainly managed within a community setting, will improve with time. An Australian community-based study suggested that one quarter of patients were in remission for two years following their initial diagnosis, while a long-term hospital-based study suggested that two-thirds of patients felt they had improved over a 14-year follow-up period.

In contrast, a large cohort of patients, followed in a multicentre study based in specialist clinics, did not demonstrate any significant improvement with time.

Like clinical trials of drug therapy, some of the reasons for discrepancies between hospital and community outcomes may reflect a selection bias; those with more disabling symptoms being over- represented among patients seen in specialist centres. One recent and unexplained finding was that people who describe widespread chronic pain have an increased mortality, which was primarily owing to an increased risk of malignancy when compared to people with either localised pain or people who were free from pain. This affected all tumour types and no clear explanation for this finding has yet been made.7

* Management

The management of fibromyalgia is a complex challenge. The key to obtaining a favourable outcome is to give the patient an early and clear explanation of the symptoms, spelling out the message that the patient can expect to improve.

This approach should be coupled with reassurance about their causes and a sympathetic approach using simple remedies. Many patients and their families are concerned that their symptoms reflect a serious or potentially life-threatening condition. They are often reassured when provided with a clear diagnostic label and knowledge that these more serious conditions have been excluded.

A good history is very important because unexpected or unrecognised pathology can occur. For example, a history of a road traffic accident, neck injury or lateralisation of pain and discomfort should encourage efforts to exclude cervical disc or bony pathology. We have seen a number of cases where, despite a diagnostic label of fibromyalgia (occasionally long-term), a compressive cervical disc lesion has been demonstrated.

It is important to accept the patient's symptoms as genuine and to emphasise that their normal blood results are in keeping with a diagnosis of fibromyalgia. We attempt to explain symptoms to patients in terms of abnormalities in sleep and of central pain processing. Many patients can understand how these abnormalities, particularly of sleep, may contribute to the way in which they feel and this leads naturally into a discussion of possible treatment. We also explain that affective problems are common in all chronic disease and may make many of the symptoms worse.

Amitriptyline is the most beneficial agent and can be introduced by explaining its sedative and central pain effects. We normally introduce a low dose and increase this gradually over a period of three months. If no effect is seen at this time, the drug can be withdrawn. If the patient feels that it is helpful, we continue it for up to one year.

If mood disorders are a major component, we treat this appropriately, often using an SSRI.

It is important to explain the potential side-effects of all drug therapy, because there is evidence that this group of patients are more likely to experience side-effects.

We use group sessions emphasising modest exercise, often as water- based activities initially, and a combination of education and CBT as adjuncts to these drug therapies.

There is no approach to the diagnosis and treatment of fibromyalgia that is universally accepted. This is understandable in the current situation where fibromyalgia is ill-defined and even less well understood. Despite this negative assessment of our knowledge of the condition, it is clear that, using an approach such as we have outlined, there are grounds for optimism with respect to alleviation of symptoms and minimising anxiety in a large percentage of cases.

The recent BMJ article describing an increased mortality in these patients emphasises the necessity for further research and the allocation of extra resources to confirm and expand our current knowledge.7

Fibromyalgia: a controversial diagnosis

Fibromyalgia was formally defined by the American College of Rheumatology (ACR) in 1990, although the antecedents of this syndrome can be traced back to conditions such as fibrositis and neurasthenia, which were described over 100 years ago.3

The ACR defined fibromyalgia patients as having widespread pain of at least three months duration. Pain should be present on both sides of the body, and be present above and below the waist. It must involve axial skeletal pain, such as anterior chest wall pain or pain along the spine.

In addition, pain should be present upon firm palpation in at least 11 of 18 specified sites termed tender points (see figure 1).

These criteria were primarily introduced to define fibromyalgia and aid clinical research into the condition. Many practitioners are now prepared to make the diagnosis of fibromyalgia in the presence of a typical history but with fewer tender points.

Despite adoption of a formal definition, the diagnosis remains controversial.4 There is continuing debate about whether fibromyalgia is a real condition or an artificial construct, not least because the tender points that are used to make the diagnosis are common within the general population who do not have other symptoms of fibromyalgia.

Irrespective of this controversy, there is no doubt that the symptoms of the condition can have a major impact upon the quality of life of an affected individual and are disabling in the most severe cases.

References

1 Croft P, Schollum J, Silman A. Population study of tender point counts and pain as evidence of fibromyalgia. BMJ 1994;309(6956): 696- 699

2 Goldenberg DL. Fibromyalgia syndrome a decade later: what have we learned? [see comments]. [Review] [156 refs] Arch Intern Med 1999;159(8):777-785

3 Wolfe F, Smythe HA, Yunus MB et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33(2):160-172

4 Quintner JL, Cohen ML. Fibromyalgia falls foul of a fallacy. Lancet 1999;353(9158): 1092-1094

5 Bennett RM. Emerging concepts in the neurobiology of chronic pain: evidence of abnormal sensory processing in fibromyalgia. Mayo Clin Proc 1999;74(4):385-398

6 Leventhal LJ. Management of fibromyalgia. Ann Intern Med 1999;131(11):850-858

7 Macfarlane GJ, McBeth J, Silman A. Widespread body pain and mortality: prospective population study. BMJ 2001;323(6956): 662-664

Useful information

1 Fibromyalgia Association UK, PO Box 206, Stourbridge, West Midlands DY9 8YL; Tel: 01384 820 052

2 The Arthritis Research Campaign, PO Box 177, Chesterfield, Derbyshire S41 7TQ; Tel: 01246 558 033

3 Coping with Fibromyalgia. Beth Ediger (auth). Toronto: LRH Publications, ISBN 0-9695785-0-4