Fibromyalgia

Fibromyalgia syndrome

Fibromyalgia syndrome is complex and often poorly understood. It commonly presents in applicants for ill health retirement or income protection claims or claims for total and permanent disability. It is important to appreciate the multiple factors involved in the condition, its presentation and severity, and what should be considered when advising pensions trustees and insurers.

The condition is relatively common, although studies suggest it is both overdiagnosed and underdiagnosed. It is generally considered substantially more common in women who make up 80-90% of those diagnosed. The prevalence is estimated at between 0.5% and 10% of the population depending on the criteria used for diagnosis. A study comparing those clinically diagnosed with fibromyalgia and patients assessed using validated diagnostic criteria for fibromyalgia found not only that the ratio was closer to 60% female, but that many of the patients diagnosed were unaware they had fibromyalgia (Wolfe et al., 2018).

Chronic widespread pain, a feature of fibromyalgia but without the other factors, is substantially more common with estimates up to 24% of the population. It is defined as pain lasting three months or longer, located axially, above and below the waist and on both left and right sides of the body. Most estimates are between 10% and 15%, prevalence is again higher in women with possible sociocultural variation (Mansfield et al., 2016). Fibromyalgia sits at one end of a spectrum of polysymptomatic distress including chronic widespread pain.

Diagnosis

Diagnosis of fibromyalgia has changed significantly over the past few decades as we have learned more about what the condition is, and is not, and identified diagnostic approaches that are more or less sensitive and specific to the condition. The first attempt by the American College of Rheumatology (ACR) in the mid-90s focused primarily on ‘tender points’ however this is no longer used as it fails to acknowledge the wider issues of physiological and psychological factors. The condition is not simply a ‘pain problem’ it is primarily a condition of distress where pain is part of the presentation. Distress will reflect the journey the patient has followed, the traumas and stressors, learned behaviors and predispositions, and may well result in the patient focusing more on one aspect of symptoms than another. Sleep disturbance may be a major factor, or cognitive dysfunction may be the most significant symptom.

Diagnostic criteria were adjusted in 2010 when the ACR updated the criteria to include a widespread pain index (WPI), assessing pain in 19 specified body areas over the past week, the symptom severity score (SS) relating to fatigue, cognitive dysfunction and waking unrefreshed and adding these scores (Wolfe et al., 2010).

The difficulty with this approach is that diagnosis is entirely subjective, for a condition where central sensitization exaggerates the pain and fatigue experience. Pain is often assessed using a visual analogue pain scale, and clinicians will all be familiar with patients reporting very high scores when they appear remarkably unaffected by the pain they are reporting.

The result is often that patients report high levels of symptoms and substantial distress but remain able to engage with normal daily activities including work. A major study found that between 65 and 70% of patients remain able to work despite symptoms. Studies also show that reported symptoms vary, patients often talking about good and bad days, but also having periods of time when they are able to function at a higher level with fewer symptoms and periods when they are more distressed by their symptoms with difficulty coping with simple tasks, often referred to as ‘flares’.

There are other conditions that present with similar symptoms, and these should be excluded before fibromyalgia is diagnosed. These include the inflammatory joint diseases and connective tissue disorders, although it is not unusual for patients with these autoimmune disorders to have an element of central sensitization, and for specialists to diagnose fibromyalgia alongside the autoimmune disorder. Hypothyroidism can cause fatigue and musculoskeletal pain, and patients with variable thyroid function such as those with Hashimoto’s thyroiditis may present with symptoms for several years until their thyroid condition has stabilized usually with thyroxine but sometimes liothyronine as well.  

The latest International Classification of Disease (ICD) criteria now group several conditions together as primary pain syndromes, where pain is the primary problem and is not driven by another disease. These conditions include tension headache, irritable bowel syndrome, low back pain, temporomandibular disorders and bladder pain syndrome. Patients with fibromyalgia often present with these conditions alongside their fibromyalgia diagnosis.

Causes and treatments for fibromyalgia

The general view is that there are no clear identifiable biomarkers for the condition. It cannot be considered a ‘disease’ as a result, however many consider it to be a condition with a physiological basis rather than psychosomatic. There are, however, multiple factors associated with the condition including genetic predisposition, psychological traits, a history of trauma or stress particularly in childhood, infective, immunological, dietary, neurological, and physiological differences between cases and controls.

Heritability of fibromyalgia has been estimated at around 50%. It is unclear to what extent this might be learned behavior; however, there are specific genetic markers. It is likely that environmental triggers play a key role alongside genetic factors including physical trauma, infections, psychological trauma, the microbiome, diet, and obesity.

Neurotransmitter dysregulation has been observed in multiple studies. It is unclear whether this is ‘cause’ or ‘effect’, and how reversible these changes might be. Low serotonin is likely to be significant, although a Cochrane review found no benefit from SSRIs (Walitt et al., 2015). Some patients have heightened sensitivity to noradrenaline-provoked pain. There does appear to be benefit from SNRIs. Duloxetine, particularly at a dose of 60mg daily can be of benefit (Migliorini et al., 2023) although the effect may be relatively minor and only some patients may benefit (Welsch et al., 2018).

All studies point to central sensitization as the main biological issue in fibromyalgia rather than any peripheral pathology, although a peripheral nociceptive pathology may well provide the initial stimulus to developing the condition. This central sensitization is now regarded as a third type of pain, separate from nociceptive (caused by inflammation or tissue damage) and neuropathic (due to nerve injury) and is termed nociplastic pain. Various mechanisms for this are postulated, including neurotransmitter dysregulation, particularly dopamine pathways. The evidence for pain mechanisms demonstrates that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, with many traditional pain modulators targeting this process. Once signals reach the brain, other brain areas appear to be responsible for control of and sensitivity to pain, such as the mesolimbic system. The amygdala is involved too, and there are links between dopamine pathways, endorphins and stress that are likely to explain the part played in past stress and trauma, chronic current stress, and the link between stressful events and a flare or relapse in symptoms. There may well be genetic factors involved that lead to low pain tolerance, and these interact with stress-related hyperalgesia leading to widespread pain. None of these studies identify a clear definitive cause, or biomarker, but do represent factors likely to be playing a part in the development and persistence of chronic widespread pain (Chen et al., 2009).

Another aspect of centrally modulated pain is the effect of exercise, and the part played by the rostral ventromedial medulla and N-Methyl-D-Aspartate (NMDA) receptors. Exercise generally promotes analgesia; however, fibromyalgia patients often report exercise intolerance leading to a sedentary lifestyle that in turn exacerbates painful conditions. There is some evidence that muscle contraction in fibromyalgia patients fails to activate pain inhibitory mechanisms while it increases pain thresholds in controls. Further evidence suggests that while exercise promotes pain inhibition, this effect is reduced as exercise reaches levels of fatigue (Lima et al., 2017). This is likely to be the main issue in ‘boom and bust’ reported by both fibromyalgia and ME/CFS patients and explains the key beneficial role of pacing when engaging in any exercise program. Optimizing exercise in fibromyalgia will lead to pain reduction and an improvement in overall physical function and physical fitness.

Psychosocial processes may also independently develop and maintain chronic pain (Edwards et al., 2016, Flor, 2003, Malfliet et al., 2017).

Multiple variations in immune function have been noted. Oxidative stress and mitochondrial dysfunction has been considered (Pieczenik and Neustadt, 2007). A blunted cortisol response may be a factor. In most studies the differences have not been sufficient to explain the overall severity of the condition but may well play a part in the development and persistence of symptoms (Úbeda-D'Ocasar et al., 2020). In many cases the differences may represent a result of behavioral change rather than the cause. There does appear to be a link with menopause, and particularly with low progesterone, and with the balance between progesterone, testosterone, and cortisol.

Central nervous system inflammation is likely to play a part in fibromyalgia, as a result of dysfunctional immune pathways or exogenous factors impacting inflammation. The gut biome has been much studied recently with increasing evidence of a major impact on health that includes the ability to cope with stress and pain. Gut microbes produce hormones and neurotransmitters that directly stimulate afferent neurons sending signals via the vagus nerve and may have a central neurotoxic effect. The result can influence sleep, stress reactivity, memory, mood, and cognition (Galland, 2014). Patients in general distress are more likely to report symptoms related to infection and seek treatments leading to often inappropriate antibiotic prescribing. Repeated courses of antibiotics can severely disrupt the gut biome. Studies to date suggest that while gut biome disruption does not cause chronic widespread pain it is likely to play a role, with therapeutic opportunities (Freidin et al., 2021). Nutritional tools could include dietary changes, prebiotics and probiotics, and even fecal transplants.

Sleep dysfunction may play a major role in both the development and persistence of symptoms, and therapies aimed at improving sleep can play a significant role in improving both pain and fatigue. There is some evidence that melatonin levels are reduced in fibromyalgia, with improvements in both sleep and pain reported after treatment with Agomelatine (De Berardis et al., 2015). Cognitive dysfunction in particular is related to poor sleep. Tricyclic antidepressants can substantially improve sleep with a corresponding major improvement in function although the side effects can be counterproductive. Good sleep hygiene is important.

Cognitive dysfunction is often reported in fibromyalgia and can represent the most disruptive symptom in relation to daily activities and work. There is evidence demonstrating moderate impairment in cognition in fibromyalgia (Bell et al., 2018). The mechanisms postulated for this include hippocampus dysfunction related to excessive NMDA activation and stress maladaptation. The impact of pain experience, ‘neural noise,’ may also play a role, with neuronal and attentional resources diverted to pain, limiting availability to drive other cognitive responses (Ibraheem et al., 2021). There also appears to be a relation between high BMI and cognitive dysfunction (Muñoz Ladrón de Guevara et al., 2018). The typical cognitive dysfunction reported in fibromyalgia is not unique to the condition but is often reported in relation to other conditions including ME/CFS. Studies show a high correlation between subjective cognitive dysfunction and high counts of somatic and psychological symptoms, and overall cognitive dysfunction is better predicted by simple symptom scores, not by scores of pain extent (Wolfe et al., 2021).

Alongside the likely impact of obesity on inflammation, there is evidence that high BMI impacts exercise levels, pain severity, stiffness, fatigue, physical functioning, sleep, cognitive dysfunction, and quality of life in fibromyalgia patients. Few studies have looked at the benefits of weight loss in fibromyalgia, but there is preliminary evidence suggesting benefit of weight loss in improving symptoms and function (D'Onghia et al., 2021).

Alongside this complex aetiology are a myriad of therapies all with evidence of significant benefits but no simple ‘cure’ that leads to a resolution of symptoms. Therapies include exercise, psychological therapies, antidepressants, cannabinoids, gabapentinoids, dietary change, ketamine, hyperbaric oxygen, and transcranial stimulation.

Many therapies traditionally tried for chronic widespread pain, particularly opioids, are largely ineffective but have a major side effect profile. Patients reporting ‘brain fog’ are in many cases reporting the side effects of opioids, gabapentinoids or antidepressants rather than a symptom of the condition itself. Opioids are no longer recommended as treatments for either fibromyalgia or chronic pain conditions, with insufficient evidence to recommend them and significant adverse effect profiles (Ngian et al., 2011, NICE, 2021). The recent increase in gabapentinoids has largely been driven by the need to avoid over-prescribing and long-term prescribing of opioids. Gabapentinoids act centrally on the voltage-gated calcium channels and NMDA receptors to downregulate excitatory neurotransmitter release, primarily developed for their antiepileptic effect but also reducing the likelihood of central sensitization and helping with the management of neuropathic pain. They remain useful but probably have a limited role in fibromyalgia and are primarily of use in pain associated with slow-wave sleep deficits. They have significant issues related to their side effect profile. Care should be taken before prescribing, and many patients improve in function, particularly cognitive function, when doses are reduced or treatment stopped (McAnally et al., 2020, NICE, 2021).

Recent studies suggest there may be benefits from repetitive transcranial magnetic stimulation or direct current stimulation (Giorgi et al., 2022).

While chronic widespread pain is the hallmark of the condition there are other common symptoms reported including fatigue, cognitive dysfunction or ‘brain fog’, sleep disturbance and heightened sensitivity to tactile stimuli. Symptoms are often associated with other chronic conditions including headaches, irritable bowel syndrome, temporomandibular joint disorders, anxiety, and depression. Some clinicians will regard these as separate conditions to be managed separately. Others will regard them as facets of one overall condition of distress and symptom sensitivity. The increasing shift towards holistic therapy should enable a better approach. This shift has been particularly noted in the provision of pain services in the UK where they were traditionally delivered by sole practitioners, usually anaesthetists specializing in pain, following more traditional biomedical approaches. The introduction of the NICE guidelines for management of chronic pain alongside the latest research findings have seen a notable shift to a biopsychosocial approach where the addition of psychotherapy, physiotherapy and occupational therapy and even nutritionists and dieticians has played a major role in improving outcomes and helping patients understand the biopsychosocial nature of their condition, the factors that have affected them on their journey into chronic pain, and the factors likely to help them find a better path (NICE, 2021).

Diagnostic and prognostic formulation

It is likely that the condition is not the result of one single factor, but of a journey through trauma and stress, with a genetic predisposition and psychological traits of catastrophisation and hypervigilance and pain avoidance. This could be considered to generate a ‘nociplastic phenotype’, a person vulnerable to developing nociplastic pain. There is some evidence for a reproducible neural signature for this state, possibly present in children at risk of subsequently developing fibromyalgia syndrome (López-Solà et al., 2017). An environmental trigger such as infection with immune system dysregulation, or a traumatic injury, or a disease process such as lupus may lead to progressive changes in central brain function and a dysfunctional pain processing system. Chronic stress may be the primary initiating factor. Past experiences of trauma and stress may lead to increased pain processing or reduced pain tolerance, and the presence of post-traumatic stress with ongoing triggers or ongoing symptoms reflecting a disrupted hypothalamo-pituitary-adrenal (HPA) axis may play a role.

None of these studies have identified one clear cause, suggesting that multiple factors are involved in developing the condition, and in the severity of symptoms reported, and therefore multiple therapeutic options need to be considered.

In any condition with a significant psychosocial component where beliefs and barriers play a role, engagement and compliance with treatments may not be optimum. Where a patient has developed central sensitization, a complete reversal is only noted in around 10% (Walitt et al., 2011). It is, however, difficult to distinguish between the chronic persistent symptoms of fibromyalgia and the normal symptoms experienced by everyone from time to time. It is inappropriate to regard a ‘cure’ as the only endpoint in treatment for a condition where there are no clear biomarkers to define the disease, the only measures are subjective, and a key feature of central sensitization is an exaggerated perception of symptoms.

Another challenge when assessing a biopsychosocial condition is the impact of friends, family and treating clinicians. When all around are reinforcing illness behavior it is very difficult to either engage with recovery or show improvement. Many patients remain substantially affected by symptoms while continuing to engage with therapy with the result that treating clinicians may well only see patients for a period of a few years while they are seeking treatment. Many patients realize that no treatment is really making any difference, stop attending specialist clinics and stop seeking new treatments from their GPs. At this point, they are more likely to develop acceptance and begin to re-engage with daily activities and work, and this process can take many years.

The overall result is that many GPs see patients who have a diagnosis of fibromyalgia in the past but who are now rarely attending for any pain-related condition and appear to be engaging fully with home life and work. Likewise, many occupational physicians see employees with a history of fibromyalgia but who are fully capable of their work roles, including physically demanding roles. Epidemiological studies tend to work with data that often represents past recorded conditions rather than current function, and we cannot directly relate healthcare data to employment data. It is not therefore readily possible to assess the lifetime course of fibromyalgia in relation to function rather than symptoms.

The pensions or insurance assessment

The key issue when considering pensions and insurance claims is not the symptoms reported, but function. Most people are able to continue working with pain and fatigue, and the same applies to patients with fibromyalgia. There is good evidence that physical exercise is beneficial in reducing pain, improving function, and improving mental health. Engaging in work is not harmful and will be beneficial. Most patients should therefore be capable of remaining in work and will benefit from doing so.

Claimants will normally present at a point where they are not working. It is important to assess why and how they have reached this point, and to determine the stage in their fibromyalgia journey. Are they currently experiencing major psychological stressors? Is it the stress of work that is the primary problem? Are there major personal stressors, reaching a point where the patient simply cannot cope with work? Is there a clear pattern in their symptom development and progression that supports their claim that they cannot work?

A physical examination of the patient can be fraught with difficulties. They will often state ‘you can see I am in pain’, and their colleagues and managers will say likewise. We cannot, of course, see pain, all we can see is pain behavior, and we often see significant overlay making it difficult to come to any objective conclusion. Patients often used to report their pain as ‘10/10’ on the visual analogue scale, insisting it is worse than childbirth pain, but other behaviors observed or reported do not support such a high level of pain. Some even used to say 11/10 or 12/10. One even told me her pain was always 10/10 but when she recently fractured her wrist, the pain was 100/10. It is much less common for patients to report pain levels of 10/10 now, and many websites advise patients with fibromyalgia what to say to their doctors, advising against reporting pain levels of 10/10, instead recommending 7/10 or 8/10. It is then difficult to determine whether the patient is reporting what they have been advised to report or their actual pain experience.

It is also important to consider not only the factors that have led to their current state of distress, but whether a change in these factors will improve their ability to cope with symptoms. The main therapies currently recommended are treatment with SNRIs, particularly Duloxetine, treating sleep disturbance with tricyclic antidepressants particularly Amitriptyline, psychological therapies to help them develop coping strategies, particularly cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT), and progressive exercise. Pacing is usually the starting point for progressive exercise, helping them gain confidence in activity, increasing at their own pace as they find the balance that suits them and progressively improving fitness. The main tailored exercise programs of benefit include stretching, aerobic, and strength training.

Other treatments may help, and it is important to determine what may be of benefit and what should be tried including dietary change and weight reduction. Beliefs and behaviors play a key role in the development of central sensitization and are as likely to play a key role in choice of treatment, engagement with treatment and treatment outcome. The placebo effect of dietary supplements and complementary therapies may help significantly.

Assessments for pensions and insurance should include a thorough history, including past trauma and stress, the psychological and psychiatric history, responses to therapy, current personal circumstances, co-morbidities, work history and circumstances, and beliefs and behaviors.

The epidemiology for fibromyalgia indicates that most patients are able to work and will be able to continue working. Where work is particularly arduous or stressful, there may be good reasons why they cannot continue and are permanently incapable of that role. However, they may well still be capable of less physical or less stressful roles and will benefit from continuing to work. If they have become incapable of working, is this likely to be a short-term reaction to circumstances or does it represent a clear progression of their condition that is unlikely to improve sufficiently to enable work engagement?

Most pensions assessments involve a timeline when considering permanence. A return to work-fitness is not going to be rapid. Most patients are likely to find their own path to an improvement in function, others will benefit from therapeutic input. They will need time to access treatment, time to engage with treatment, time to adjust and adapt their lives and time to improve physical fitness and confidence. It is unlikely that this will be achieved in a matter of months. It may be feasible to reach work fitness within a year for those already functioning well, but others may well take three to five years to reach a point where they can engage in gainful employment. Some will only be capable of limited hours, perhaps between ten and twenty hours a week. Time to pension age may well be significant; those with less than five years to go may be much less likely to be capable of gainful employment before normal pension age than those with twenty or thirty years to go.

A report accompanying a pension assessment should include the diagnostic and prognostic formulation, consideration of treatments likely to be of benefit and reasons why they can or cannot meet the criteria for early payment of pensions benefits or insurance.

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