Education and debate

ABC of Rheumatology: FIBROMYALGIA SYNDROME

Fibromyalgia is common in hospital practice. It is rarely reported in children, and most patients are in their 40s or 50s. In all settings there is a strong female preponderance (about 90%). It is well reported in the United States, Canada, and Europe, but racial and social predisposition have not been adequately addressed.

Symptoms are variable. Pain and fatiguability are usually prominent and associated with considerable disability and handicap. Although patients can usually dress and wash independently, they cannot cope with a job or ordinary household activities. Pain is predominently axial and diffuse but can affect any region and may at times be felt all over. Characteristically, analgesics, non-steroidal anti-inflammatory drugs, and local physical treatments are ineffective and may even worsen symptoms.

Patients often have a poor sleep pattern with considerable latency and frequent arousal. Typically they awake exhausted and feel more tired in the morning than later in the day. Unexplained headache, urinary frequency, and abdominal symptoms are common and may have been extensively investigated with no cause found. Patients usually score highly on measures of anxiety and depression.

Although the term fibromyalgia syndrome is not ideal, it does not imply causation and describes the commonest symptom. Idiopathic diffuse pain syndrome, generalised rheumatism, and non-restorative sleep disorder are terms that are increasingly preferred by some.

View larger version (61K): [in this window] [in a new window]   Typical hyperalgesic withdrawal response by patient with fibromyalgia. (Picture reproduced with patient's permission.)

  Prevalence of fibromyalgia
  Rheumatology clinics                        20%
  Internal medicine clinics                    6%
  Family practice clinics                      2%
  General medical inpatients
    (United Kingdom)                           5%
  General population
    (Swedish city, British general practice)   1%

  Principal symptoms of fibromyalgia
  Pain
  Predominantly axial (neck and back), but may be all over
  Often aggravated by stress, cold, and activity
  Often associated with generalised morning stiffness
  Often with subjective swelling of extremities
  Paraesthesiae and dysaesthesiae of hands and feet
  Fatiguability
  Often extreme, occurring after minimal exertion
  Non-restorative sleep
  Waking unrefreshed
  Poor concentration and forgetfulness
  Low affect, irritable, and weepy
  Headache
  Occipital and bifrontal
  Diffuse abdominal pain and variable bowel habit
  Urinary frequency
  Urgency (day and night)
  Dysmenorrhoea

Clinical signs

Clinical findings are unremarkable, and the principal positive sign is the presence of multiple hyperalgesic tender sites. In normal subjects these tender sites are uncomfortable to firm pressure, but in patients with fibromyalgia similar pressure produces a wince or withdrawal response. The degree of pressure is clearly important; delivery of standard pressure with a spring device (dolorimeter) is ideal, but reasonable palpation suffices for clinical purposes.

  Principal clinical findings
  * Discordance between symptoms and disability and objective findings
  * No objective weakness, synovitis, or neurological abnormality
  * Multiple hyperalgesic tender sites (axial and upper and lower limbs)
  * Pronounced tenderness to rolling of skin fold (mid-trapezius)
  * Cutaneous hyperaemia after palpation of tender sites or rolling of skin
  fold
  * Negative control (non-tender) sites (such as forehead, distal forearm,
  and lateral fibular head)

  Common hyperalgesic tender
  sites
  * Low cervical spine (C4-C6 interspinous
  ligaments)
  * Low lumbar spine (L4-S1 interspinous
  ligaments)
  * Suboccipital muscle (posterior base of skull)
  * Mid-supraspinatus
  * Mid-point of upper trapezius
  * Pectoralis insertion--maximal lateral to
  second costochondral junction
  * Lateral epicondyle--tennis elbow sites, 1-2
  cm distal to epicondyle
  * Gluteus medius--upper, outer quadrant of
  buttock
  * Greater trochanter
  * Medial fat pad of knee

Hyperalgesia at one or two sites in the same quadrant often results from periarticular lesions or referred tenderness from an axial structure. In fibromyalgia, however, hyperalgesia is widespread and symmetrical. The number of tender sites required by different diagnostic criteria varies, but eight or more are sufficient for clinical purposes. Importantly, hyperalgesia is absent at sites that are normally non-tender. If a patient claims to be tender all over, fabrication or psychiatric disturbance (psychogenic rheumatism) is more likely. Osteoarthritis and periarticular syndromes are common and may be present as incidental findings or as a trigger for the syndrome.

View larger version (91K): [in this window] [in a new window]   Common hyperalgesic tender sites.

View larger version (29K): [in this window] [in a new window]   Palpation of hyperalgesic tender sites: (top left) medial fat pad of knee, (top right) site of muscle insertion at occiput, and (left) greater trochanter of femur.

Differential diagnosis

Other conditions that may present with widespread pain, weakness, or fatigue should be excluded by a limited investigational screen. Further tests may be warranted if a patient's history and examination suggest a predisposing or coexistent condition. Undertaking all investigations together reinforces the patient's confidence in the accuracy of the diagnosis and is preferable to a drawn out sequence of tests. Fibromyalgia may superimpose on pre-existing painful conditions such as osteoarthritis or cancer but usually affects subjects with no other diagnosis (primary fibromyalgia).

  Differential diagnosis and investigations
  Differential diagnosis        Investigations
  Hypothyroidism                Thyroid function tests
  Systemic lupus erythematosus  Full blood count
                                Erythrocyte sedimentation rate and
                                blood viscosity
                                Antinuclear factor
  Inflammatory myopathy         Creatine kinase concentration
  Hyperparathyroidism           Calcium concentration and alkaline
  Osteomalacia                  phosphatase concentration

Nature of fibromyalgia

The pathogenesis of the syndrome remains unclear. Clinical heterogeneity is pronounced, and multiple factors are likely to relate to its development and chronicity. Depending on the predominant symptom, fibromyalgia may be categorised under various diagnostic labels. These conditions overlap and probably represent different expressions in a spectrum of abnormality. Medicine has a traditional bias towards a pathological explanation of disease, but with fibromyalgia there is no investigational evidence of overt inflammatory, metabolic, or structural abnormality and the problem appears functional rather than pathological.

  Diagnostic terms that often include patients with
  fibromyalgia
  Principal presenting symptom  Diagnostic label
  Locomotor pain                Psychogenic rheumatism
                                Fibrositis
                                Pain amplification syndrome
  Fatigue                       Myalgic encephalomyelitis
                                Chronic fatigue syndrome
  Headache                      Tension headache
  Abdominal pain and bowel      Irritable bowel syndrome
  disturbance
  Frequency and nocturia        Female urethral syndrome

Sleep disturbance

A strong association with sleep disturbance is suggested by:

* An increased frequency of non-restorative sleep

* Electroencephalographic evidence of reduced deep non-rapid eye movement (non-REM) sleep with interruption by a waves (a-d intrusion)

* Reproduction of fibromyalgia symptoms and hyperalgesic tender sites in normal subjects by selective deprivation of non-REM (but not REM) sleep.

Chronic non-restorative sleep (union sign)f8^-has been suggested as a possible cause. Various factors (such as regional pain syndrome, bereavement, and anxiety) cause reduced deep sleep, with resultant somatic symptoms and fatigue. Once reduced sleep has been established, reduced activity, declining aerobic fitness, and pain encourage perpetuation of this aberrant sleep pattern.

View larger version (95K): [in this window] [in a new window]   Possible mechanism of induction and perpetuation of fibromyalgia.

Other possible causes

Deficiency of serotonin (or its precursor tryptophan) and other abnormalities of the neuroendocrine axis have been proposed as mechanisms to explain both the sleep disorder and pain associated with fibromyalgia. Whether these reported abnormalities are cause or effect remains uncertain.

Viral aetiology has been proposed for patients with some forms of chronic fatigue syndrome, but evidence for triggering viral infections in most patients with fibromyalgia is lacking.

Affective symptoms are common, though whether they are primary or secondary remains unclear. In fibromyalgia the predominance of locomotor pain, presence of multiple hyperalgesic tender sites, development after selective sleep deprivation, and different response to treatment argue for differentiation from anxiety or depression with somatisation.

  Whether the cause of fibromyalgia (such
  as signal misinterpretation,
  psychoneuroendocrine disorder, or
  aberrant pain mech-anism) is peripheral
  or central remains unclear and may differ
  between patients

Management

There is no specific treatment for this condition, but individual patients may be considerably helped. The single most important intervention is a comprehensible explanation. Most patients expect a pessimistic cause for their devastating symptoms, and they should be reassured that the pain does not reflect cancer, inflammation, or structural damage. An explanation based on poor sleep and reduced fitness is readily understood and helps patients to rationalise their symptoms, disability, and treatments. It is helpful to include family members. Inquiry about life events may reveal problems that merit open discussion and counselling. Patients with sublimated anxiety are more likely to improve if their anxiety is identified and successfully addressed.

  Principal strategies for
  managing fibromyalgia
  * Educate patient
  * Educate patient's family
  * Avoid unnecessary investigations and
  treatments
  * Use interventions to correct non-restorative
  sleep, improve aerobic fitness, and reinforce
  intrinsic locus of control

Controlled trials have confirmed the usefulness of low dose amitriptyline or dothiepin (25-75 mg at night) and a graded exercise programme to increase aerobic fitness.

Amitriptyline--The dose used is lower than that for depression. Its efficacy may be due to its normalising effects on the sleep centre or pain gating at the spinal cord level. Interestingly, cyclobenzaprine (a tricyclic muscle relaxant with no antidepressant action) is also effective. If these drugs are ineffective after a trial of four to six weeks, further drug treatment should be avoided. Benzodiazepines and other hypnotics have no place in treatment.

Increasing aerobic exercise is intended to improve sleep and restore fitness. It may initially exacerbate symptoms, but patients should be encouraged to continue despite pain (the opposite advice to that for someone with synovitis or joint damage). An important element is that the locus of control is now within the patient--it is up to them, not doctors or drugs, to improve their situation.

Operant and other illness behaviour is common. This needs to be recognised and eliminated by educating family members.

Coping strategies (such as meditational yoga) may permit patients to better control the extent to which pain and fatigue intervene in their life.

  Interventions for managing
  fibromyalgia
  Low dose amitriptyline
  Initially a limited trial of 4-6 weeks
  Graded aerobic exercise regimen
  Individualised to patient
  Set specified targets that increase weekly
  Encourage small amounts often
  Encourage continuation despite pain
  Retrain to avoid operant behaviour
  Coping strategies
  Meditational yoga
  Behavioural therapy

Prognosis

The prognosis for fibromyalgia is poor. In one British study less than one in 10 patients diagnosed in hospital lost their symptoms over five years. Nevertheless, suitable advice can help most patients to learn to cope better with their condition and, importantly, to avoid further unnecessary investigations and drug treatments.

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