Introduction
Definition
Pathophysiology
Drug treatment
Non-drug treatment
Diagnosis
Conclusion
References

Introduction

Fibromyalgia is part of the spectrum of central sensitivity syndromes and has symptoms comprising generalised muscular pain, disordered and unsatisfying sleep, fatigue and foggy thinking, together with a variety of intrusive comorbidities that combine to make life difficult for both patient and doctor.

The symptoms, although unpleasant, seem non-specific initially and therefore it is often a year before presentation to a GP. It then takes on average a further two years with multiple investigations and consultations involving several doctors before a diagnosis of fibromyalgia is agreed.3 There is evidence that a physical or mental trauma, or infection can act as trigger, but there is also a familial relationship with genetic susceptibility through gene polymorphisms involved in the serotonin and dopamine pathways.4-6

Population surveys in several countries have found similar levels of self-reported symptoms equating to fibromyalgia that vary mainly according to method of estimation. They give an overall prevalence of 3-8% in women and 1-5% in men, but if restricted to disease formally diagnosed as fibromyalgia then the rates are only around 2% in women and 0.2% for men. However there is a clear age relationship with the prevalence peaking in 50-70 year olds, and 10% of European women reporting fibromyalgic symptoms at age 80.7,8

Definition

An early description (17th century) of a fibromyalgia-like illness was termed muscular rheumatism.9 Since then it has had various names including psychogenic rheumatism and fibrositis, and it seems very similar to the popular Victorian malady of neurasthenia. High profile possible sufferers include Darwin and Florence Nightingale; indeed, the International Fibromyalgia Awareness Day is on her birthday (May 12). However it was not until 1990 that formal criteria for the diagnosis of fibromyalgia were specified by the American College of Rheumatology as: widespread pain for at least three months, above and below the waist, involving both sides of the body and including the axial skeleton; plus pain to palpation at 11 or more of 18 specific (bilateral) sites. They also stated that having another disorder still allows the additional diagnosis of fibromyalgia.10

In formulating these criteria Wolfe et al reported that, not surprisingly, many sufferers (65%) have “pain all over”, but in addition 76% complain of stiffness, particularly in the mornings and after even mild exercise, and also paraesthesia (58%). However, the major complaint apart from pain is fatigue (85%) associated with disturbed and unrefreshing sleep (75%). Also, a variety of co-morbidities are complained of notably: headache (51%), irritable bowel syndrome (35%), anxiety (51%), depression, temporo-mandibular joint disorder and restless legs syndrome.10 These symptoms and co-morbidities were not included in the 1990 criteria, though clinicians often made the diagnosis on widespread pain taken in conjunction with the fatigue, sleep disorder and other related symptoms without palpating all the prescribed points.

As a result, 20 years after the original, the American College published revised criteria that score fatigue, unrefreshing sleep and cognitive disorder as well as counting the number of painful areas.11 Additionally, there is a score for the number of co-morbidity symptoms (out of about 40 commonly found). A checklist is available to download from Fibromyalgia Network.12 This gives a much more effective overall view of the spectrum of “fibromyalgianess”,13 but does emphasise the overlap of symptoms with chronic fatigue syndrome, post-viral syndrome, myalgic encephalomyelitis, post-traumatic stress disorder, and related conditions such as myofascial pain syndrome and irritable bowel syndrome. Indeed, Yunus has proposed that all these should be considered as part of a spectrum of “Central Sensitivity Syndromes” in which there is cerebral sensitisation with neuro-endocrine dysfunction, resulting in multiple symptom reporting.14 There seems also to be a spectrum within fibromyalgia itself: up to five subgroups have been described,15,16 and it is possible that each will respond differently to medical treatment.

Because central sensitisation can occur following a variety of physical and mental stresses, the diagnosis of fibromyalgia can be made in addition to another condition, most commonly rheumatoid or osteo-arthritis, lupus or other rheumatoid disease, but the 2012 American National Health Survey found that 23% of fibromyalgics had diabetes, 30% had asthma, 56% had migraines and 62% depression.17 In addition 39% smoke, 47% are obese and 54% have hypertension with 16% other heart disease, so it is not surprising that fibromyalgia is a predictor of both myocardial infarction and stroke.18,19

Pathophysiology

Patients with fibromyalgia display hyperalgesia, allodynia and expansion of cortical receptive fields, so painful stimuli are felt more intensely,20 non-painful stimuli such as touch and light pressure are felt as pain, and stimuli outside a sensitive area may also be felt as pain. Functional MRI investigations have demonstrated that compared to normal subjects fibromyalgic patients do indeed feel pain from a 50% lower level of stimulus, and that connections between areas of the brain involved in pain perception and those concerned with emotion, thinking and memory are augmented.21 This results in mental concentration on the pain, with catastrophic thinking enhancing otherwise mild pain to become intolerable. In addition it gives rise to the poor memory and foggy thinking (dyscognition) complained of by fibromyalgics that has been termed “fibrofog”.22

The m-opioid receptors in areas of the brain key to the regulation of pain and emotion appear to be switched off, despite an increase in endorphin levels.23 In addition, serum levels of the neurotransmitters serotonin and noradrenaline are reduced in fibromyalgia. These are involved in the perception of pain via the descending inhibitory pathway, and also in sleep, fatigue, cognition and mood. Substance P levels, on the other hand, are increased. This enhances pain transmission, stress and anxiety.6 So, in total, these neurotransmitter changes, together with the central neurological changes, conspire to promote the symptoms of generalised pain, anxiety, poor sleep, fatigue and foggy thinking.

Sleep disruption experiments can reproduce these fibromyalgic symptoms,24 and patients show an EEG pattern similar to deep-sleep deprived subjects with arousal-type a waves intruding on the normal deep-sleep d waves.25 Additionally disturbed sleep results in upregulation of pro-inflammatory cytokines which enhance pain, disturbing sleep still further.26

Drug treatment

The main pharmacological treatment, therefore, aims at boosting serotonin and noradrenaline levels. The most popular drug for fibromyalgia is amitriptyline, which inhibits both serotonin and noradrenaline transporters.27 It also has affinity for histaminic, cholinergic and other adrenergic receptors, so initially has the side effects of heavy sedation, dry mouth and constipation, however these usually wear off after a couple of weeks and a low dose of 10-25mg taken at night lessens the problem while aiding sleep. Modern serotonin-boosting antidepressant drugs, although more expensive, appear to have fewer side effects for fibromyalgic patients.28 Duloxetine, a serotonin and noradrenaline reuptake inhibitor (SNRI), has been specifically approved by the US Food and Drug Administration for use in fibromyalgia. Pregabalin, another approved drug, is an antiepileptic that acts by lowering calcium ion influx at nerve terminals thus reducing release of glutamate and substance P. It is used to treat neuropathic pain, and also acts as an anxiolytic and mood stabiliser with the added benefit that it reduces symptoms of a frequent comorbidity of fibromyalgia: restless legs syndrome.29,30 It is doubly effective when taken in combination with an SNRI if the patient can tolerate both.31

As inflammation is not a major feature of fibromyalgia, steroids are unsuitable and the non-steroidals are not usually of benefit unless there is co-morbid arthritic or rheumatoid disease. Strong opioids are rarely helpful due to the lack of m-opioid receptor availability. They are inappropriate for the chronic pain of fibromyalgia, while reducing mobility and worsening fatigue. However, some patients find buprenorphine patches a help as this has some anti-hyperalgesic effect. Intriguingly recent work has demonstrated the opioid antagonist naltrexone to have significant analgesic effects in fibromyalgia.32 At a low dose of 3-5mg it appears to have immune cell (microglial) receptor antagonism in the central nervous system, reducing pro-inflammatory cytokine production, reversing hyperalgesia and improving the so-called “sickness behaviour” attributed to microglia activation. This could prove an effective future treatment, but major trials are needed. The only true analgesic generally of help in fibromyalgia is tramadol (often combined with paracetamol) which, as well as being a weak opioid, has SNRI action.33 However beware of serotonin toxicity in patients also taking other serotonin-boosting medication.

Despite the availability of apparently powerful drugs, benefit can be claimed for only half of those able to take them,31 and even then success is only partial and almost never a cure. A major problem is that some fibromyalgic patients suffer with the co-morbidity of “multiple chemical sensitivity” and many are oversensitive to most drugs, so that excessive side effects prevent their taking any of the more useful medications, or mean reducing the dosage to a level that offers minimal benefit. Non-drug and complementary therapies thus offer a prospect for complication-free help to modify frustratingly intrusive symptoms and should be regarded as the mainstay of treatment, certainly in the elderly (Box 1).34,35

Non-drug treatment

A particularly frustrating feature of fibromyalgia, in common with chronic fatigue syndrome, is that following mild exercise such as supermarket shopping or light gardening, the patient may feel racked with pain and be bed-ridden for the next couple of days. Nonetheless, graded exercise is a vital element in rehabilitation. To be acceptable this requires confidence in the physician and effective education about the condition, so that there is understanding that upsets following exercise have no long-term effects and become less intense if the exercise has been carefully graded and, if possible, taken in conjunction with hydrotherapy or at least a warm bath for post-exercise relaxation. Cognitive behavioural therapy has proved helpful in the psychological acceptance of an exercise regime and in modifying the response to pain, encouraging distraction techniques and reducing catastrophic thinking (“Oh dear, I can feel the pain coming on - it’s going to get worse - it is worse - it’s getting unbearable!”).36

Of working age patients, 56% report being unable to work because of their fibromyalgia (71% for men). This substantially reduces social contact and results in isolation, particularly as a high proportion (49%) are unmarried, divorced or separated, allowing them to concentrate more on their disability.17 The distraction of work and social contact has proved beneficial in reducing pain and improving rehabilitation through enhanced self-confidence. So it is important to encourage patients to socialise and take some employment, even if only helping at a charity: employers nowadays are legally required to make allowances for disability.

Among the complementary therapies, acupuncture has the best clinical evidence. Indeed around 20% of fibromyalgics have tried acupuncture within two years of diagnosis.37,38 It has been found to boost the synthesis and release of serotonin and noradrenaline, and gentle acupuncture can enhance oxytocin levels, with consequent calming effects.39-41 Thus it seems well placed to offer benefits to fibromyalgia sufferers, particularly as it appears to have synergistic action with the most common fibromyalgic drug treatment, amitriptyline,42 and has been shown effective for several of the common co-morbidities such as headache, restless legs syndrome and irritable bowel syndrome.

Most fibromyalgic patients have more than one co-morbidity, some several, so making improvements in these, by whatever means, can make a substantial improvement in quality of life. Also, since sleep disturbance is a major factor in fibromyalgia, attention to standard sleep hygiene can pay dividends, and melatonin can be helpful for some patients. But overall, the recommendation is that a combination of therapies, physical, psychological and drugs, offers the best chance of significant improvement, both for fibromyalgic symptoms and quality of life.43 However, to gain the greatest benefit, treatment should be started as soon as possible, before central sensitisation has become firmly established.

 

BOX 1:  SUITABLE TREATMENTS FOR FIBROMYALGIA

               Education as standard for all treatments

Physical and Psychological

Level of evidence

Cognitive Behavioural Therapy (CBT)

High

Graded exercise/ Walking

High

Hydrotherapy/ Balneotherapy/ Swimming

Moderate

Acupuncture/ Electroacupuncture

Moderate

             

  Combine some or all of the above and add drug therapy if necessary

 

Drug therapy

 

Amitriptyline 10-25mg at night

High

Replace with Duloxetine (SNRI)

High

Add Pregabalin (or Gabapentin)

High

Tramadol (or Tramacet) for analgesia if necessary

Moderate

 

Diagnosis

As the symptoms of fibromyalgia, particularly in the elderly, may be found as an accompaniment of other disease, they should be sought if a patient is complaining of pain and exhaustion beyond that expected after treatment of their original problem. However other causes of myalgic pain must be considered before diagnosing fibromyalgia either alone or in addition.

Polymyalgia rheumatica has similar symptoms but a more dramatic presentation and greater muscle stiffness. It is readily treatable and should not be missed. Other rheumatic diseases may be associated with fibromyalgia, particularly rheumatoid arthritis, systemic lupus erythematosis and polymyositis. Fibromyalgic-like symptoms can also be produced by some infections such as hepatitis, infectious mononucleosis and Lyme disease. All can be identified or excluded with simple investigations such as ESR, full blood count, liver function tests and possibly C-reactive protein, rheumatoid factor or antibody tests. A sub-set of fibromyalgia patients has mild hypothyroidism, so thyroid function tests and subsequent treatment can make a difference to symptoms of fatigue. Apart from these, be aware of drug-induced myalgias, notably statins, ACE inhibitors and cocaine. Having eliminated the above, it is important then to accept the diagnosis of fibromyalgia, stop further, more intrusive, investigation and institute a treatment regime as soon as possible.34,44

Due to the ready psychological influencing of fibromyalgia, and its subjective diagnosis and assessment with no evidence from blood tests or imaging to back it up, there has been doubt as to its status as a real disease. Illness or disorder might be more appropriate terms, though there is no doubt about its being a disability.14 In addition, the mere name fibromyalgia seems to give permission to some patients to retire from active life and live on disability payment, a course which cognitive behavioural training may be used to try and avoid, but a consequence is that some doctors are reluctant to make the diagnosis.

Certainly the causal attribution and diagnostic label can influence recovery,45,46 and “fibromyalgia” does have negative connotations, but there is evidence that following diagnosis there is reduction in the former high level of health-care costs and that patients with delayed diagnosis report their pain and other symptoms as more severe and their satisfaction with treatment less. So an early diagnosis with initiation of therapy is important, although if it is considered that a patient would not respond well to the term fibromyalgia, then the diagnosis could reasonably be given as “muscular rheumatism” or “central sensitivity syndrome” and if appropriate upgraded later to fibromyalgia.

The symptoms of fibromyalgia are very sensitive to stress and to external elements such as the weather (there is usually improvement in the summer), family problems, or legal issues. So disability levels fluctuate, sometimes quite widely, making response to treatment difficult to interpret. Nonetheless, a useful aid to assessment of response is the validated, though self-scored, Fibromyalgia Impact Questionnaire which gives a global assessment, psychological as well as physical, and provides a reasonable overview of quality of life and coping ability.47 Versions of this questionnaire are available for download from Arthritis Research.48

Conclusion

Fibromyalgia is an unsatisfactory disorder to treat. Because of their disabling symptoms the patients are unreliable in attending appointments; they are often unable to take medication, and when they do, are only partially responsive to it. Some of the more effective treatments are non-pharmacological: graded exercise, hydrotherapy and cognitive behavioural therapy, but it is a struggle to maintain these. Despite this, patients are usually very grateful for a sympathetic doctor who understands and believes in their distress, even if there is little apparent change in their symptoms.

Conflict of interest: none declared

 


Dr Simon Hayhoe

Formerly of Pain Management Department, University Hospital, Colchester

simonhayhoe@doctors.org.uk

 


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 First published in May 2016