Fibromyalgia today

Fibromyalgia syndrome (FMS), formerly called fibrositis syndrome or generalized soft tissue rheumatic pain syndrome, is no longer classified as an independent clinical picture, but rather as a clinical complaint complex. The focus is on pain in various parts of the body with additional accompanying symptoms/vegetative complaints such as fatigue, sleep disturbances, cognitive impairment, and usually also clustered psychiatric comorbidities. The medical diagnosis of fibromyalgia syndrome is controversial. This article provides an update on the epidemiology, pathogenesis, diagnosis, and therapy.

In 1990, a task force of the American Rheumatologic Society (ACR) attempted an operationalization of “fibromyalgia.” Consequently, the pain had to be present for more than three months and distributed over different parts of the body. Thus, of 18 predefined tendon attachment points (so-called tender points), at least eleven had to be painful on palpation. These so-called ACR criteria, which were never intended to define a circumscribed clinical picture, were increasingly used precisely for this purpose from the mid-1990s and were finally also included in the ICD-10 under “other diseases of soft tissue, not classifiable elsewhere” (M 79.90). Thus, fibromyalgia was defined as a rheumatologic disease. Even before the ACR criteria were established, there were indications that FMS might be a somatization disorder in which dysfunctional stress processing is probably pathogenetically significant.

Epidemiology

Fibromyalgia syndrome (FMS) predominantly affects women. In clinical studies, fibromyalgia is predominantly found in young or middle-aged individuals, but population surveys indicate that prevalence tends to increase with age, reaching a maximum in those over 60 years of age. An onset already in childhood and adolescence is significantly rarer, but increasingly common. The earlier thesis that fibromyalgia heals with age has not been confirmed.

Pathogenesis

The causes of fibromyalgia are still unknown. It is well established that infections are not a risk factor for developing FMS (EBV, parvovirus, hepatitis, Lyme disease, etc.). There are also no consistent structural or functional abnormalities in muscle tissue. A muscular cause of FMS could already be excluded in the mid-1990s. In a recent review, amplification of afferent pain signals in the spinal cord is implicated as a key mechanism in the development of chronic pain in rheumatic diseases, including. FMS described.

In search of specific serological and biochemical abnormalities, a number of different parameters in serum and CSF have been investigated by numerous research groups. Various neurotransmitters seem to play a role in this. In particular, higher concentrations of so-called substance P and lower levels of serotonin, norepinephrine, and dopamine metabolites are detected in fibromyalgia patients in individual studies compared with healthy controls.

Recent magnetic resonance studies show abnormal signal transmission in fibromyalgia patients in brain areas involved in the transmission of pain and emotion such as the amygdala, thalamus, and insular cortex. The biochemical changes in cerebrospinal fluid and the disturbance in cerebral signal transduction are associated with fibromyalgia, but it is not clear from the observations whether this is a causal relationship or a coincidence. Morphological changes in the musculature, especially evidence of an inflammatory process, have long been ruled out. It is postulated again and again that a restricted oxygen supply of the musculature could be the cause of pain due to a reduced capillarization (ischemia pain). However, corresponding studies proved that this is rather due to the lack of physical training (deconditioning). At the same time, it could be shown that the limited muscle strength is just as centrally controlled as the lack of relaxation between the individual muscle contractions. Inflammatory rheumatic diseases have an increased likelihood of developing additional FMS. Therefore, a distinction used to be made between primary and secondary fibromyalgia.

Serological and biochemical abnormalities

Various parameters in serum and CSF have been studied in recent years with the aim of finding clinically useful “markers”. However, this has not yet been achieved. Autoantibodies to serotonin, gangliosides, phospholipids, etc. were sought. Also examined were antithromboplastin, antipolymer, and various other antibodies, occasionally finding elevated levels in FMS patients without replication in further studies to date. Similarly, no abnormalities were found in studies of the relevance of antinuclear and antithyroid antibodies. The relevance of substance P, a neuropeptide secreted by axon stimulation in the CSF, was also investigated. Although some studies have demonstrated significantly elevated levels, it was noted that this is not a parameter specific to FMS, as it has also been found in other chronic pain conditions such as chronic headache, chronic fatigue patients, after whiplash, and especially in depressed and anxiety patients. No specific relevance in FMS has been demonstrated for other neuropeptides either. The relevance of the cytokine IL-8 is still unclear. Its serum level correlates more frequently with the extent of FMS symptoms, but this cannot be explained by a possible depressive comorbidity. In contrast, the cytokine IL-6, known as a stress messenger, was mostly within the normal range in these studies. Decreased tryptophan levels or disorders of tryptophan metabolism were found by two research groups, but the specificity of these findings has not yet been adequately clarified. Similar findings apply to the reduced levels for serotonin and metabolites in serum and cerebrospinal fluid already described in previous studies.

Genetic predisposition

Overall, some findings suggest the pathogenetic significance of genetic polymorphisms in the serotonergic, dopaminergic, and catacholaminergic systems, which may contribute to enhanced pain perception. This could also explain the clustered occurrence of affective and anxiety disorders in FMS. The genetic factor seems to be greater in fibromyalgia than in chronic fatigue syndrome (CFS) or chronic tension headache.

Sleep

Sleep disorders basically lead to an increased sensitivity to pain. This is true for both REM and non-REM sleep deprivation. About two thirds of all FMS patients suffer from non-restorative sleep resp. Sleep disturbances, which is why sleep disturbances were considered a primary cause for the development of FMS in earlier years. Various “intrusions” mean impairment of restful deep sleep and lead to symptoms of insufficiently restful sleep the next day. A vicious circle of stress and sleep impairment occurs. However, this alpha-delta sleep has been observed in other disorders such as CFS, sleep apnea syndrome, restless leg syndrome, and to that extent is not specific to FMS. Other authors have shown that there is a direct relationship between insecure-anxious attachment behavior and alpha-delta sleep abnormality.

Stress Processing Disorder

As another pathogenetically significant dimension, the relationship between FMS and stress processing system was investigated. In this regard, the activation of the HPA axis (hypocampus-amygdala) plays a role, which is described especially in patient groups traumatized in childhood. Regarding the activation of the HPA axis, the results in most studies are striking, i.e. a dysfunction of the HPA axis is now considered to be certain. However, the observed abnormalities go in opposite directions, with some studies yielding overactivation and others underactivation. This heterogeneity of the results can be explained by the three confounding variables: Depressive comorbidity, childhood trauma, and duration of stress exposure. The permanent exposure to stressors leads to a persistent hyperreactivity of the HPA axis, before it develops into a reduced responsiveness in the sense of a burn-out. This development can lead to severe depression, CFS, or even FMS through counter-regulation.

Central sensitization

All the aforementioned pieces of the mosaic have been integrated into an increasingly clear pathogenetic picture in recent years by the results of neuroimaging studies. It had already been obvious for some time that not only the increased pressure sensitivity of the soft tissues considered in the ACR criteria, but also a lowered pain threshold as well as increased pain sensitivity to cutaneous stimuli exist in FMS patients. Several studies show that FMS patients suffer from dysfunction of the pain modulating system at the CNS level. In addition, it has been observed in individual studies that there is increased sensitivity not only to pain but also to other sensory stimuli, such as noise or unpleasant odors. Recent results from PET and SPECT studies also indicate reduced blood flow in several brain areas, especially in the thalamus. Consistent with this, reduced gray matter density in the thalamic region of FMS patients has been described. The total volume of gray matter was also significantly reduced. The longer an FMS exists, the greater the loss of gray matter. From the point of view of disturbed stress processing, the reduced density of gray matter in the parahippocompal gyrus is of particular interest, since similar abnormalities had also been observed in post-traumatic stress disorders and in CFS. The neurotransmitters dopamine and serotonin play an important role in this process. Indirect evidence for dopamine system dysfunction comes from imaging studies showing impaired cerebral blood flow in the caudate nucleus region in FMS patients. This brain region is particularly rich in dopamine receptors. In brain metabolism, dopamine is significant for pleasure and well-being, motivation, and the control of motor functions. Moreover, it has recently been suggested that dopamine in the basal ganglia may also be significant for pain modulation. The dopaminergic system is closely linked to the opioid system. A reduced number of opioid receptors indicates increased pain sensitivity.

Psychological comorbidity

As early as the 1990s, studies observed psychological comorbidity in FMS patients in the form of depressive and especially anxiety disorders. One such increases the number of pain points as well as the severity of the pain experience. It leads to functional limitation and significantly higher fatigability. This is also associated with a higher degree of catastrophizing as a predominant coping strategy. There is increased body-related self-observation and greater interference from pain symptomatology, as well as disruption of self-esteem regulation.

Diagnostics

Within the framework of a biopsychosocial understanding of the disease, the family doctor must first explore the extent of the pain symptoms (e.g., with the aid of a body diagram in which the patient draws in his various pain localizations). A pain diary is useful as a supplement. Laboratory tests should include blood count, BSR, CRP (to rule out inflammatory rheumatic system disease), creatine kinase (muscle disease), TSH (thyroid metabolism disorders), and calcium (hypercalcemia). The determination of antibodies associated with inflammatory rheumatic diseases is not useful as a routine test. Due to the high comorbidity of anxiety disorders and depression, their careful exploration is required.

Imaging techniques are not currently useful for detecting fibromyalgia. The diagnosis is made solely on the basis of clinical features as well as exclusion criteria. However, fibromyalgia syndrome may occur together with other diseases such as osteoarthritis, rheumatoid arthritis or collagenoses, especially once as a prodromal stage of an inflammatory rheumatic systemic disease.

Therapy

There is still no golden key in the treatment of fibromyalgia. Both non-drug and drug treatment strategies are recommended. For some sports, there is strong to moderate evidence of efficacy, especially for endurance training and adapted strength training, whereas no efficacy has been proven for passive therapeutic measures such as massage, chiropractic therapy, etc. The evidence on the effectiveness of cognitive behavioral therapies is strong and consistent and, according to several authors, represents an important element of effectiveness. However, from a review on the effectiveness of mind-body therapies such as hypnotherapy, biofeedback, and stress reduction, only moderate evidence emerges.

Various medications such as analgesics, opioids, antidepressants, and anticonvulsants are available to treat the wide range of symptoms associated with fibromyalgia. It has long been documented that NSAIDs have virtually no effect in FMS.

Treatment with analgesics is also not very effective in FMS patients and should be limited in time, if at all. There is no indication for opiates. The only opioid with evidence-based efficacy in fibromyalgia is tramadol, also in combination with acetaminophen (^Zaldiar®). In practice, weak opioids such as codeine or dihydrocodeine (Codicontin®, ^Paracodin®) are also frequently prescribed. The effects of antidepressants have been demonstrated in numerous systemic reviews of randomized controlled trials. Guidelines support the use of amitriptyline (^Saroten®), fluoxetine (^Fluctine®), paroxetine (^Deroxat®), duloxetine (^Cymbalta®), and venlafaxine (^Efexor®) – they should be used primarily in the presence of coexisting psychiatric comorbidity or to modulate sleep disturbance. Systematic reviews also demonstrate efficacy of antiepileptic drugs such as pregabalin (^Lyrica®) and gabapentin (^Neurontin®) in fibromyalgia.

An essential task of the family doctor or practicing specialist in primary care is to provide the patient with comprehensive information about the biopsychosocial relationships in FMS presented. This already starts with the clarification of the diagnostic labeling – information and education work against catastrophizing coping and offer the affected patient the possibility of active cooperation in the therapy. For the treatment of fibromyalgia, medications have been much better studied than non-drug interventions. However, because study periods are usually short, no conclusions can be drawn about the benefits and risks of drug treatment over a period longer than six months. Published studies regarding long-term pain and quality of life are mostly still insufficient.

Literature:

1. Arnold LM, et al: A randomized double-blind placebo controlled trial of duloxetine in the treatment of women with fibromyalgia with or without major depressive disorder. Pain 2005; 119: 5-15.
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3. Cieza A, et al: ICF Core sets for chronic widespread pain. J Rehabil Med 2004; Suppl 44: 63-68.
4. Gracely RH, et al: Pain catastrophizing and neural responses to pain among persons with fibromyalgia. Brain 2004; 127; 835-843.
5. Hemmeter UM, et al: Sleep disturbances in chronic pain and rheumatism. Rheumatology DIA – GM 1995; 16: 613-618.
6. Richards SCM, Scott DL: Prescribed exercise in people with fibromyalgia: parallel group randomised controlled trial. BMJ 2002; 325: 185.
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9. Egle UT, Echa-Egle ML, Nickel R: Fibromyalgia syndrome-a stress processing disorder. Swiss Archives of Neurology and Psychiatry 2011; 162(8); 326-337.

CONCLUSION FOR PRACTICE

• Predominantly women are affected by fibromyalgia syndrome.
• The causes are still unknown. Meanwhile, various studies show that FMS patients suffer from dysfunction of the pain modulating system at the CNS level. PET and SPECT studies also indicate reduced blood flow in several areas of the brain (particularly the thalamus). Gray matter in the thalamic region has reduced density and lower total volume in FMS. In addition, sleep disorders, stress processing disorders, and psychological comorbidities play a role.
• Diagnosis is based on clinical features as well as exclusion criteria.
• Treatment uses both non-drug (exercise, cognitive behavioral therapy) and (better studied) drug treatment strategies such as analgesics, opioids, antidepressants, and anticonvulsants.

A RETENIR

• Le syndrome fibromyalgique concerne essentiellement les femmes.
• Ses causes demeurent inconnues. Diverses études montrent que les patients atteints de SFM souffrent d’un dysfonctionnement du système de modulation de la douleur au niveau du SNC. Les examens de TEP et TEMP montrent également une perfusion sanguine réduite dans diverses régions du cerveau (en particulier dans la région du thalamus). La substance grise dans la région thalamique présente en cas de SFM une densité réduite et un volume global réduit. De plus, les troubles du sommeil, les troubles de la gestion du stress et les comorbidités psychiques jouent un rôle.
• Le diagnostic est posé à partir de critères cliniques et de critères d’exclusion.
• Le traitement comprend aussi bien des stratégies thérapeutiques non médicamenteuses (sport, thérapie de comportement cognitif) que médicamenteuses (mieux étudiées) telles que les analgésiques, les opioïdes, les antidépresseurs et les anticonvulsifs.

GP PRACTICE 2014; 9(11): 36-40