Most physicians, especially those in orthopedics, rheumatology, pain medicine and general practice, have experienced patients coming to the hospital, usually complaining of generalized pain that lasts for a longer period of time and is accompanied by other related symptoms, such as poor sleep quality, easy fatigue and depression. There is a term for this type of disease, called fibromyalgia. This group of patients can be a challenge for clinicians.
Diagnosing fibromyalgia has been highly controversial for a long time, and many scholars have questioned whether fibromyalgia can be considered as a separate disease. However, one thing is certain: the above symptoms do exist in patients with fibromyalgia. The mechanisms by which fibromyalgia occurs are not well understood, and therefore, its optimal treatment remains highly controversial.
What is fibromyalgia and what is its incidence?
In daily practice, fibromyalgia is diagnosed if a patient has a history of chronic pain that is widespread, with pressure pain in multiple muscle areas visible on examination or symptoms such as fatigue, cognitive dysfunction, or sleep disturbance. For some patients, there may be a combination of muscle pressure and symptoms associated with the above.
Chronic widespread pain is epidemiologically defined as pain that persists for at least 3 months, is distributed on both sides of the torso, and involves at least above and below the wrist. Epidemiological data from several countries show that widespread chronic pain is a relatively common problem, with a prevalence of about 10%. It is important to note, however, that not all patients with widespread chronic pain have fibromyalgia disease.
According to the diagnostic classification criteria for fibromyalgia published by the ACR in 1990, its prevalence in the population is only 2%. According to the diagnostic criteria published by the ACR, the diagnosis of fibromyalgia is very simple (sensitivity 88.4%, specificity 81.1%): a patient with widespread chronic muscle pain is diagnosed if tenderness is present in more than 11 of the 18 specified locations.
However, these diagnostic criteria have some drawbacks: it is very difficult to standardize tenderness during the physical examination, and tenderness may be present in some parts of the normal population; this diagnostic criterion does not include other clinical aspects of fibromyalgia, such as sleep disturbance and fatigue.
For general practitioners, the ACR’s 2010 revised diagnostic criteria may be more practical. In the latest revised version of the diagnostic criteria, the body is no longer required to have a specific site of tenderness, instead, the body is divided into 19 regions, and the number of pains in different regions is summed up to form a widespread pain index; at the same time, other combined symptoms are included to form a symptom severity score (including fatigue, sleep disturbance, cognitive impairment, etc.). The two scores were combined into a simple survey scale with a maximum score of 31.
Based on these diagnostic criteria, two recently completed statistical analyses found that the population prevalence of fibromyalgia was around 2.1% in Germany and 6.4% in Minnesota, USA.
In the German study, the investigators used a score of 12-13 as a cut-off point to distinguish those who met the ACR 2010 criteria from those who did not; however, the authors also noted that there was no significant difference in clinical symptoms between those above and below this cut-off point (sharp division), so the authors concluded that fibromyalgia patients are not an isolated disorder, but may be an extreme upper limit of the population of patients with multisymptomatic depression.
Who is at risk for fibromyalgia?
Fibromyalgia typically occurs in women, and a minnesota population survey found that about 7.7% of women and 4.9% of men met the ACR 2010 diagnostic criteria for fibromyalgia, but a concurrent analysis of medical records found that in the same population, only 27% of patients who met the ACT 2010 diagnostic criteria were diagnosed with fibromyalgia, a proportional This is inconsistent with the actual findings, as the prevalence was only 2% for women and 0.15% for men.
It is also worth noting that the majority of patients in the medical records were diagnosed with fibromyalgia at a young age, but the actual survey found that the incidence of fibromyalgia increased with age, with the highest incidence occurring over the age of 60 years, which may be explained by the fact that in older patients, multiple limb pains are often diagnosed as arthritis rather than fibromyalgia.
Fibromyalgia is not limited to developed countries, as a large sample study in Bangladesh (n=5211) with a high return rate (99%) showed an overall prevalence of 4.4% in rural populations, 3.2% in poor urban areas and 3.3% in affluent urban areas, according to the ACR 1990 diagnostic criteria, and these prevalence rates are generally consistent with those in Western countries.
How does fibromyalgia occur?
The exact pathogenesis of fibromyalgia is not yet understood. These patients do not have persistent structural or functional abnormalities in their muscles, but their pain transmission and disposition mechanisms in the central nervous system are impaired. A recently completed review found that amplification of nociceptive transmission signals in spinal cord segments plays a very important role in the development of chronic pain in patients with rheumatic diseases, including fibromyalgia.
Psychological and sociological factors also have an impact on pain amplification mechanisms, and demographic studies have shown that these factors are associated with the onset and persistence of fibromyalgia.
However, not all psychosocial stresses of the same magnitude in the normal population lead to the development of fibromyalgia, and therefore genetic factors also play a role in its development.
A study of family genetic genealogy of fibromyalgia patients in the United States found that patients with fibromyalgia were 13.6 times more likely to have siblings with fibromyalgia than the normal population. A correlation has been found to exist with fibromyalgia in a region of chromosome 17.
A pain experiment found that patients with fibromyalgia had pain stimulation scores in cold water that were more than 50% higher than normal; there is also evidence that pain transmission inhibitory pathways are not as effective in people with fibromyalgia as they are in the normal population; and patients with fibromyalgia have higher levels of substance P in the cerebrospinal fluid than the normal population, while concentrations of metabolites such as serotonin, norepinephrine, and dopamine The concentrations of metabolites such as serotonin, noradrenaline, and dopamine are lower.
The mechanism of action of many clinical drugs used in the treatment of fibromyalgia is based on this evidence.
Functional MRI studies of fibromyalgia patients have revealed abnormal signal activity in functional brain regions where pain transmission is disposed. Recent resonance boxplots have found higher concentrations of glutamate and glutamate in the right amygdala of the human brain in fibromyalgia patients than in normal subjects, but there is no significant correlation between the two.
Despite these findings, it is too early to say whether they are a specific mechanism for the pathogenesis of fibromyalgia.
How is fibromyalgia diagnosed?
Some people believe that the diagnosis of fibromyalgia is not particularly helpful in clinical practice. However, in the authors’ experience, many patients can obtain some mental relief after a clear and detailed explanation of fibromyalgia by their physician, and patients diagnosed with fibromyalgia ensure that they are relieved of the mental aspects of their diagnosis by excluding tumors or other diseases.
Studies have reported that patients with a diagnosis of fibromyalgia have significantly fewer visits and medical expenses after the diagnosis of the disease.
There are no specific blood or imaging methods to diagnose fibromyalgia, and C-reactive protein concentrations and ESR are not usually elevated in these patients. The diagnosis of fibromyalgia is based solely on the patient’s clinical symptoms.
The ACR 1990 diagnostic criteria recommended testing 18 specified body regions for tenderness to determine if a patient could be diagnosed with fibromyalgia, which is a convenient and valid diagnostic method, but it is true that close to 25% of patients in the clinic have fibromyalgia but do not have 11 specific muscle pressure points.
Although the ACR organization improved the diagnosis of fibromyalgia in 2010, it is currently not used much in clinical practice. In patients with chronic widespread pain, asking patients about the presence of sleep disturbances, tenderness, and memory or thinking disorders can be extremely helpful in making a diagnosis according to the ACR fibromyalgia 2010 version diagnostic criteria.
Fibromyalgia is not an exclusive diagnosis and can exist in combination with other conditions. A survey using the ACR 2010 diagnostic criteria found that approximately 17% of patients with osteoarthritis, 21% of patients with rheumatoid arthritis, and 37% of patients with systemic lupus erythematosus had comorbid fibromyalgia.
Therefore, careful identification of all symptoms and application of clinical examination measures such as complete blood count, basal biochemical products, and inflammatory factors are required before establishing the diagnosis of fibromyalgia in patients.
Thyroid function tests and vitamin D levels can be helpful in the diagnosis of certain diseases, and special care should be taken when using autoimmune indicators for the differential diagnosis in such patients, and the significance of autoimmune indicators for the diagnosis should be considered in a comprehensive manner, unless the patient has an autoimmune disease. Patients with fibromyalgia who test positive for autoimmune antibodies but who do not have autoimmune disease may be misleading in their diagnosis.
Patients with inflammatory osteoarthritis may also present with stopping point pressure pain similar to fibromyalgia, so a specialist consultation is required for the diagnosis of these patients. In particular, fibromyalgia can occur in patients with a previous diagnosis of another disease, such as rheumatoid arthritis, and should be taken into account in the event of diminished efficacy of treatment in such patients.
In conclusion, the diagnosis of fibromyalgia should be considered when the patient has chronic widespread pain that cannot be explained by other diseases, especially if the patient complains of pain that is disproportionate to the physical examination, or if there is a combination of sleep dysfunction, fatigue, or muscle tenderness. A specialist consultation is not necessary for the diagnosis of fibromyalgia, but should be considered if there is doubt about the patient’s diagnosis.
Fibromyalgia treatment
There are many hot spots in the treatment of fibromyalgia. The functional prognosis of all clinical symptoms should be reported for high-quality RCT studies. Tables 1-4 show all the current literature related to the treatment of fibromyalgia.
1. What is the effectiveness of nonpharmacologic treatments for fibromyalgia?
Non-pharmacologic treatments for fibromyalgia can be psychological or physical. Physical methods of treatment include active and passive modalities.
Physical therapy (active)
Functional exercise is recommended for all patients with fibromyalgia. A systematic review analysis found that regular aerobic exercise (20 min/day, 2-3 times/week for at least 2.5 weeks) improved patients’ clinical symptoms. Strength training can also reduce pain and tenderness and bring pleasure to patients, but its evidence level is low.
Physical therapy (passive)
A systematic analysis and two clinical studies provided moderate clinical evidence supporting bathing therapy for fibromyalgia. Other passive physical therapies include massage, equine therapy, electrotherapy, and ultrasound therapy. However, there is less evidence to support the application of the above clinical measures.
Acupuncture
A systematic evaluation found that the strength of evidence for acupuncture for fibromyalgia was only mild to moderate. Studies found that electroacupuncture and conventional acupuncture treatments showed similar symptom improvement to the placebo group at one month post-treatment. A clinical study of moderate treatment found that acupuncture improved patients’ clinical function in the short term, but one study also found similar efficacy to the placebo group for patients treated with acupuncture for more than 6 months.
Psychotherapy
In addition to exercise, fibromyalgia can be treated through education and psychology, and behavior. Education can alleviate the tension and anxiety that patients experience because of their location, while behavioral cognitive therapy can improve patients’ pain perception.
There is strong evidence to support that disease education is significant in improving the functional prognosis of patients with the disease. Most clinical treatment programs for fibromyalgia also use disease advocacy as an effective treatment tool.
2. Pharmacological treatment of fibromyalgia
Medications used to treat fibromyalgia include analgesics, opioids, and antidepressants. Some drugs, such as pregabalin, gabapentin, serotonin and adrenaline reuptake inhibitors (milnacipran, duloxetine), can alter neurotransmitter transmission.
The effectiveness of different drugs in treating the disease varies. The choice of therapeutic agents needs to be communicated to the patient and to address the most pressing clinical symptoms as much as possible on the basis of rational drug use. In some cases, multi-drug combinations are necessary.
The drugs used to treat fibromyalgia have been associated with significant side effects along with significant efficacy. A systematic analysis found that 19% of patients achieved more than half improvement in pain on treatment, but 11% of patients discontinued use because of significant side effects.
Analgesic drugs
There is limited clinical evidence to directly support the use of paracetamol or NSAIDs in patients with fibromyalgia. In a study of 1,799 patients with rheumatic disease combined with fibromyalgia, a preference for NSAIDs was found in 60% of patients, while only 14% preferred paracetamol. Adequate communication with patients about possible efficacy and side effects is needed when prescribing NSAIDs or paracetamol for the treatment of fibromyalgia.
Opioids
The only opioid that has proven effective in the treatment of fibromyalgia is tramadol (or tramadol combined with paracetamol). In one study, the pain status of patients after 2 hours of intravenous use of tramadol was found to be similar to that of the placebo group.
There was only one RCT study of tramadol in combination with paracetamol for fibromyalgia, and the study concluded that patients benefited from the combination for 3 months. The effect of tramadol in the treatment of pain may be related to enhanced serotonin release and inhibition of adrenaline reuptake.
Despite its current clinical use, there is no evidence to support the use of weak opioids in patients with fibromyalgia. The use of strong opioids in patients with fibromyalgia should be avoided and therefore there is an addictive potential for prolonged application of opioids. It is very puzzling that opioids are not indicated for the treatment of fibromyalgia in the UK, yet they can be used in a variety of conditions for the treatment of pain.
Antidepressants
Many systematic analyses of RCTs have found antidepressants to be very effective in the treatment of fibromyalgia. One systematic analysis found a large effect of antidepressants in the treatment of pain, fatigue and sleep disorders. However, no such drugs are currently approved for use in the treatment of fibromyalgia in the UK.
A mesh analysis of RCT studies found that tricyclic antidepressants significantly reduced pain, but did not improve quality of life.
Another RCT mesh Meta-analysis found that tricyclic antidepressants reduced pain by 30% with a relative risk of 1.18. An analysis of amitriptyline drugs found a relative risk of 2.9 for reducing nonspecific pain. However, the use of morclobemide should be avoided as much as possible because of its large side effect reactions.
Antispasmodic drugs
Multiple systematic analyses have found that a second-generation antispasticity drug, pregabalin, is effective in the treatment of fibromyalgia. A systematic analysis of pregabalin (150-600 mg/day) found better relief of pain, sleep disturbance, and anxiety than the placebo group.
A systematic review of gabapentin found that its relative risk of 30% improvement in pain was 1.6. The available clinical evidence supports the use of gabapentin or pregabalin in clinical practice.