Fibromyalgia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Fibromyalgia (FM) is a disorder characterized by the presence of chronic, widespread pain and tactile allodynia. The criteria for this disease have not yet been thoroughly developed. The recognition that fibromyalgia involves more than just pain has led to the frequent use of the term “fibromyalgia syndrome.” It is not contagious and recent studies suggest that some people with fibromyalgia may be genetically predisposed. The disorder is not directly life-threatening. The degree of symptoms may vary greatly from day to day with periods of flares (severe worsening of symptoms) or remission; however, the disorder is generally thought to be non-progressive.

In 1900, the first case study of fibromyalgia was conducted. It was known by other names such as muscular rheumatism and fibrosita. In 1904, Sir William Gowers coined the term “fibrositis.” In 1976, Dr. P.K. Hench used the term “fibromyalgia” for the first time.

ICD11 classifies fibromyalgia as category of chronic widespread primary pain^[1][2].

DSM 5 divides fibromyalgia into four groups based on the differences in psychological and autonomic nervous system profiles among affected individuals. These four groups are: extreme sensitivity to pain with no associated psychiatric conditions, fibromyalgia with comorbid pain-related depression, depression with concomitant fibromyalgia syndrome, and fibromyalgia due to somatization.^[3]

 The exact cause of fibromyalgia is unknown. Multiple factors are believed to influence the development of fibromyalgia. Various hypotheses have been offered describing the pathogenesis of fibromyalgia. It is understood that Lyme disease may be a trigger of the symptoms of fibromyalgia. It is suggested that more than one clinical entity may be involved in the pathogenesis of fibromyalgia, ranging from a mild, idiopathic inflammatory process to clinical depression.

The exact cause of fibromyalgia is not known. Common trigers of fibromyalgia include is unknown physical or emotional trauma, abnormal pain response (areas in the brain that are responsible for pain may react differently in fibromyalgia patients), sleep disturbances, or infection, such as a virus, although no specific viruses have been identified as a triger of fibromyalgia.^[4][5]

Fibromyalgia must be differentiated from other diseases that present with pain, fatigue, and sleep disturbance, and symptoms of cognitive dysfunction and psychiatric disease which include rheumatoid arthritis, SLE, chronic fatigue syndrome, spondyloarthritis, and polymyalgia rheumatica.

The prevalence of fibromyalgia in the United States was reported to range from 500-5,000 per 100,000 people. Females are more commonly affected than males with a ratio of 9:1. People between 20 and 50 years old are more commonly affected. Fibromyalgia has no racial predilection.

Common risk factors in the development of fibromyalgia include stressful or traumatic events, such as car accidents or post-traumatic stress disorder (PTSD), injuries from repetitive stress on a joint such as frequent knee bending, illness (such as viral infections), or obesity. Family history of fibromyalgia is also a common risk factor.

There is insufficient evidence for the screening of fibromyalgia.

Fibromyalgia is a long-term disorder. If left untreated, chronic pain could cause permanent changes in how the body perceives pain. Complications that can develop as a result of fibromyalgia include marked functional impairment, depression, anxiety, insomnia, obesity, and allodynia. Factors associated with poor outcomes are female gender, low socioeconomic status, and being unemployed. Even with appropriate treatment, though symptoms of fibromyalgia sometimes improve, the pain may get worse and continue for months or years.

The most widely accepted set of diagnostic criteria for fibromyalgia was elaborated in 2010 by the Multicenter Criteria Committee of the the American College of Rheumatology. A patient satisfies diagnostic criteria for fibromyalgia if the following 3 conditions are met:

1. Widespread pain index (WPI) > 7 and symptom severity (SS) scale score >5 or WPI 3–6 and SS scale score >9.
2. Symptoms have been present at a similar level for at least 3 months.
3. The patient does not have a disorder that would otherwise explain the pain.

The defining symptoms of fibromyalgia are chronic, widespread pain and tenderness to light touch.

A physical examination helps not only to confirm the diagnosis of fibromyalgia but also to rule out other systemic diseases. A careful physical examination also helps in identifying associated conditions. The tender-point examination is the most important aspect of the physical examination; other aspects of the examination are typically normal in fibromyalgia patients.

Blood and urine tests are usually normal in a patient with fibromyalgia. However, tests may be done to rule out other conditions that may have similar symptoms.

There are no X-ray findings associated with fibromyalgia.

There are no CT findings associated with fibromyalgia.

There are no MRI findings associated with fibromyalgia.

There are no ultrasound findings associated with fibromyalgia.

There are no other imaging findings associated with fibromyalgia.

There are no other specific diagnostic findings associated with fibromyalgia.

There is no universally accepted treatment or cure for fibromyalgia, and treatment typically consists of symptom management. Treatment options include medications, patient education, aerobic exercise, and cognitive behavioral therapy, which have been shown to be effective in alleviating pain and other fibromyalgia-related symptoms.

Medical therapy includes analgesics, antidepressants, skeletal muscle relaxants, anticonvulsants, and anti-anxiety medications.

Although there is no universally accepted cure, some doctors have claimed to have successfully treated fibromyalgia stemming from a psychological cause. As the nature of fibromyalgia is not well understood, some physicians believe that it may be psychosomatic or psychogenic. Cognitive behavioral therapy has been shown to improve the quality of life and coping in fibromyalgia patients and other sufferers of chronic pain.

Surgical intervention is not recommended for the management of fibromyalgia.

There is no established method of prevention of fibromyalgia.

There are no specific secondary preventive measures available for fibromyalgia. However, proper treatment and lifestyle changes can help reduce the frequency and severity of symptoms. Secondary preventive measures for fibromyalgia include adequate sleep, reducing emotional and mental stress, regular exercise, following a balanced diet, and monitoring one’s own symptoms.

Several drugs, including milnacipran, guaifenesin, and dextromethorphan, are being investigated as potential therapies for fibromyalgia. Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI), and a Phase III study demonstrated statistically significant therapeutic effects of the drug as a treatment for fibromyalgia syndrome. Guaifenesin is a more controversial potential therapy, and a study by researchers at Oregon Health Science University in Portland failed to demonstrate any benefits from this treatment, though results of the study have since been contested. Dextromethorphan is an over-the-counter cough medicine that has been used in research settings to investigate the nature of fibromyalgia pain, but there are no controlled trials of its safety or efficacy in clinical use.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

In 1900, the first case study of fibromyalgia was conducted. It was known by other names such as muscular rheumatism and fibrosita. In 1904, Sir William Gowers coined the term “fibrositis.” In 1976, Dr. P.K. Hench used the term “fibromyalgia” for the first time.

• In 1900, the first case study of fibromyalgia was conducted. It was known by other names such as muscular rheumatism and fibrosita.
• In 1904, Sir William Gowers coined the term “fibrositis.”
• In 1976, Dr. P.K. Hench used the term “fibromyalgia” for the first time.
• In 1981, Dr. Muhammad B. Yunus published the “first controlled study of the clinical characteristics” of the fibromyalgia syndrome, for which he is considered “the father of our modern view of fibromyalgia.”^[1][2]
• In 1986, serotonergic and norepinephric drugs were proved to be effective for fibromyalgia.^[3]
• In 1987, American Medical Association recognized fibromyalgia as an illness and a cause of disability.
• In 1984, it was proposed that fibromyalgia syndrome and other similar conditions are connected.
• In 1990, the ACR published criteria for fibromyalgia and developed neurohormonal mechanisms with central sensitization.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

The exact cause of fibromyalgia is unknown. Multiple factors are believed to influence the development of fibromyalgia. Various hypotheses have been offered describing the pathogenesis of fibromyalgia. It is understood that Lyme disease may be a trigger of the symptoms of fibromyalgia. It is suggested that more than one clinical entity may be involved in the pathogenesis of fibromyalgia, ranging from a mild, idiopathic inflammatory process to clinical depression.^[1][2]

The exact cause of fibromyalgia is unknown. Multiple factors are believed to influence the development of fibromyalgia. Various hypotheses have been offered describing the pathogenesis of fibromyalgia. It is understood that Lyme disease may be a trigger of the symptoms of fibromyalgia. It is suggested that more than one clinical entity may be involved in the pathogenesis of fibromyalgia, ranging from a mild, idiopathic inflammatory process to clinical depression.^[3][4]

• Stress is a significant precipitating factor in the development of fibromyalgia.^[5][6][7]
• A non-mainstream hypothesis is that fibromyalgia may be a psychosomatic illness, described by John E. Sarno’s “tension myositis syndrome.”
• Sarno believes many cases of chronic pain result from changes in the body caused by the mind’s subconscious strategy of distracting painful or dangerous emotions.
• Education, attitude change, (and in some cases, psychotherapy) are treatments proposed to stop the brain from using negative strategies to process painful emotions.^[8][9]
• Robert G. Schwartz, MD, proposed an alternative view in which mind-body connections may play an important role in chronic disease (not just fibromyalgia).

• Dopamine is a catecholamine neurotransmitter known for its role in the pathology of schizophrenia, Parkinson’s disease, and addiction.
• Fibromyalgia has been commonly referred to as a “stress-related disorder” due to its frequent onset and worsening of symptoms in the context of stressful events.^[10][11]
• It was therefore proposed that fibromyalgia may represent a condition characterized by low levels of central dopamine that likely results from a combination of genetic factors and exposure to environmental stressors, including psychosocial distress, physical trauma, systemic viral infections, or inflammatory disorders (e.g. rheumatoid arthritis, systemic lupus erythematosus).^[12]
• This conclusion was based on three key observations:
  • Fibromyalgia is associated with stress.
  • Chronic exposure to stress results in a disruption of dopamine-related neurotransmission.
  • Dopamine plays a critical role in modulating pain perception and central analgesia in areas such as the basal ganglia (including the nucleus accumbens), insular cortex, anterior cingulate cortex thalamus, periaqueductal gray, and spinal cord.^{[13] [14][15][16] [17][18] [19][20][21]}
• As is the case with several neurotransmitters, there is evidence for a role of dopamine in restless leg syndrome, which is a common co-morbid condition in patients with fibromyalgia.^[22][23]
• Patients with restless leg syndrome have also been demonstrated to have hyperalgesia to static mechanical stimulation.^[24]

• Serotonin is a neurotransmitter that is known to play a role in regulating sleep patterns, mood, feelings of well-being, concentration and descending inhibition of pain.
• Accordingly, it has been hypothesized that the pathophysiology underlying the symptoms of fibromyalgia may be a dysregulation of serotonin metabolism, which may explain (in part) many of the symptoms associated with the disorder. ^[25][26]
• However, selective serotonin reuptake inhibitors (SSRIs) have met with limited success in alleviating the symptoms of fibromyalgia.

• The sleep disturbance hypothesis states that any event such as a trauma or illness that causes sleep disturbance and chronic pain may initiate fibromyalgia.
• According to the hypothesis, stage 4 sleep is critical for normal functioning of the nervous system because, in stage 4 sleep, certain neurochemical processes in the body “reset.”
• It is during that stage 4 sleep, pain causes the release of the neuropeptide substance P in the spinal cord, which leads to amplification of pain and nerves to become more sensitive to pain.
• If pain becomes chronic and systemic, this process can run out of control.
• The sleep disturbance hypothesis holds that deep sleep is critical to reset the substance P mechanism and prevent this out-of-control effect.
• The sleep disturbance/substance P hypothesis could explain “tender points” that are characteristic of fibromyalgia but which are otherwise enigmatic since their positions don’t correspond to any particular set of nerve junctions or other obvious body structures.
• The sleep disturbance hypothesis proposes that these locations are more sensitive because the sensory nerves that serve them are positioned in the spinal cord to be most strongly affected by substance P.
• The sleep disturbance hypothesis could also explain some of more general neurological features of fibromyalgia since substance P is active in many other areas of the nervous system.
• The sleep disturbance hypothesis could also explain a possible connection between fibromyalgia, chronic fatigue syndrome (CFS), and post-polio syndrome through damage to the ascending reticular activating system of the reticular formation.
  • This area of the brain, in addition to apparently controlling the sensation of fatigue, is known to control sleep behaviors and is also believed to produce some neuropeptides. Thus, injury or imbalance in this area could cause both CFS and sleep-related fibromyalgia.
• Electroencephalography studies have shown that people with fibromyalgia lack slow-wave sleep and circumstances that interfere with stage four sleep (pain, depression, serotonin deficiency, certain medications or anxiety) may cause or worsen the condition.

• An alternate hypothesis suggests that stress-induced problems in the hypothalamus may lead to reduced amounts of sleep and reduced production of human growth hormone (HGH) during slow-wave sleep.
• People with fibromyalgia tend to produce inadequate levels of human growth hormone.
• Most patients with fibromyalgia with low IGF-I levels failed to secrete HGH after stimulation with clonidine and L-dopa.
• This view is supported by the fact that hormones under the direct or indirect control of HGH, including IGF-1, cortisol, leptin, and neuropeptide Y, are abnormal in people with fibromyalgia.
• In addition, treatment with exogenous HGH or growth hormone secretagogue reduces fibromyalgia-related pain and restores slow-wave sleep, but there is disagreement about the proposition.^{[27][28][29][30][31][32]}

• The deposition hypothesis of fibromyalgia states that fibromyalgia is due to intracellular phosphate and calcium accumulations that eventually reach levels sufficient to impede the ATP process. This may be caused by a kidney defect or missing enzyme that prevents the removal of excess phosphates from the bloodstream.
• Proponents of this hypothesis suggest that fibromyalgia may be an inherited disorder and that phosphate buildup in cells is gradual but can be accelerated by trauma or illness.
• Calcium is required for the excess phosphate to enter the cells. The additional phosphate slows down the ATP process; however, the excess calcium stimulates the cell to continue producing ATP.
• The phosphate build-up hypothesis explains many of the symptoms present in fibromyalgia and proposes an underlying cause.

• Other hypotheses propose that fibromyalgia is caused by various toxins from the patient’s environment, viral causes such as the Epstein-Barr Virus, growth hormone deficiencies possibly related to an underlying (potentially autoimmune) disease affecting the hypothalamus gland, an aberrant immune response to intestinal bacteria, neurotransmitter disruptions in the central nervous system, and erosion of the protective chemical coating around sensory nerves.^[33][34]
• A 2001 study suggested an increase in fibromyalgia among women with extracapsular silicone gel leakage from implants, compared to women whose implants were not broken or leaking outside the capsule.^{[35][36][37][38]}
• Another hypothesis states that patients suffer from vasomotor dysregulation leading to improper vascular flow and hypoperfusion (decreased blood flow to a given tissue or organ).^[39]

• Fibromyalgia always a comorbid disorder, occurring in combination with another disorder that likely triggers the fibromyalgia.
• Other associated conditions include:
  • Gluten sensitivity
  • Irritable bowel syndrome
    • Irritable bowel syndrome is found at high frequency in patients with fibromyalgia and a large celiac support group survey of adult celiacs revealed that 7% had fibromyalgia.
  • Chronic fatigue^{[40] [41]}

By using self-reported “Chronic Widespread Pain” (CWP) as a surrogate marker for fibromyalgia, the Swedish Twin Registry found that a modest genetic contribution may exist:^[42][43]

• Monozygotic twins with CWP have a 15% chance that their twin sibling has CWP.
• Dizygotic twins with CWP have a 7% chance that their twin sibling has CWP.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

The exact cause of fibromyalgia is not known. Common trigers of fibromyalgia include is unknown physical or emotional trauma, abnormal pain response (areas in the brain that are responsible for pain may react differently in fibromyalgia patients), sleep disturbances, or infection, such as a virus, although no specific viruses have been identified as a triger of fibromyalgia.^[1][2]

Common trigers of fibromyalgia include:^[2]

• Physical or emotional trauma
• Abnormal pain response (areas in the brain that are responsible for pain may react differently in fibromyalgia patients)
• Sleep disturbances
• Infection, such as a virus, although no specific viruses have been identified as a cause of fibromyalgia
• Stress

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Fibromyalgia must be differentiated from other diseases that present with pain, fatigue and sleep disturbance, and symptoms of cognitive dysfunction and psychiatric disease such as rheumatoid arthritis, SLE, chronic fatigue syndrome, spondyloarthritis, and polymyalgia rheumatica.^{[1][2][3][4][5]}

Fibromyalgia must be differentiated from other diseases that present with pain, fatigue and sleep disturbance, and symptoms of cognitive dysfunction and psychiatric disease such as rheumatoid arthritis, SLE, chronic fatigue syndrome, spondyloarthritis, and polymyalgia rheumatica.^{[1][2][3][4][5]}

Disease	Differentiating signs and symptoms	Diagnostic findings
Fibromyalgia	Symptoms have been present at a similar level for at least 3 months. Chronic musculoskeletal pain with multiple tender points Stiffness, numbness, and fatigue Headaches Sleep disorder	All lab tests are normal
Rheumatoid arthritis	Multiple joint swelling Morning stiffness Rheumatoid nodules	RF or anti-cyclic citrullinated protein (CCP) antibody is positive. Markers of systemic inflammation (ESR, CRP) are typically elevated.
SLE	Maculopapular rash Multi-system involvement	Positive anti-Smith antibodies
Chronic fatigue syndrome	Fatigue plus 4 of the following symptoms: Short-term memory loss Sore throat Tender lymph nodes in the neck or armpit Muscle pain Joint pain without swelling or redness Headaches Insomnia Malaise	Diagnosis of exclusions Symptoms must present for more than 6 months
Spondyloarthritis	Axial skeletal pain and stiffness Restricted spinal motion	Elevated ESR or CRP Negative RF Bamboo spine on x-ray
Polymyalgia rheumatica	Older at onset Generalized stiffness	An elevated erythrocyte sedimentation rate (ESR) OR C-reactive protein (CRP) Response to corticosteroids
Osteoarthritis	Localized joint pain Restricted to affect joints Older at onset	X-ray of the involved joints demonstrate degenerative changes
Hypothyroidism	Systemic symptoms such as weight gain, constipation, dry skin Muscular aching and prominent fatigue that improves on replacement of thyroid hormone.	TSH is elevated and free T4 is low.
Myopathaies (polymyositis and dermatomyositis)	Pelvic and shoulder girdle muscle weakness Rash	Muscle biopsy confirms the diagnosis Elevated CPK enzyme
Neuropathy	Numbness and tingling Paresthesia	Abnormal EMG

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

The prevalence of fibromyalgia in the United States was reported to range from 500-5,000 per 100,000 persons. Females are more commonly affected than males with a ratio of 9:1. People from ages 20 to 50 are more commonly affected. Fibromyalgia has no racial predilection.^[1]

The prevalence of fibromyalgia in the United States was reported to range from 500-5,000 per 100,000 persons.

Females are more commonly affected than males with a ratio of 9:1.

People between ages 20 and 50 are more commonly affected with fibromyalgia.

Fibromyalgia has no racial predilection.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Common risk factors in the development of fibromyalgia include stressful or traumatic events, such as car accidents or post-traumatic stress disorder (PTSD), injuries from repetitive stress on a joint such as frequent knee bending, illness (such as viral infections), or obesity. Family history of fibromyalgia is also a common risk factor.^[1]

The possible risk factors for fibromyalgia include: ^[1]

• Female sex (women are more prone to have fibromyalgia than men)
• Stressful or traumatic events, such as car accidents or post-traumatic stress disorder (PTSD)
• Repetitive injuries and injury from repetitive stress on a joint, such as frequent knee bending
• Illness (such as viral infections)
• Family history
• Obesity
• Monozygotic twins have a greater risk than dizygotic twins

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

There is insufficient evidence for the screening of fibromyalgia.

There is insufficient evidence for the screening of fibromyalgia.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Fibromyalgia is a long-term disorder. If left untreated, chronic pain can cause permanent changes in how the body perceives pain. Complications that can develop as a result of fibromyalgia are marked functional impairment, depression, anxiety, insomnia, obesity, and allodynia. Factors associated with poor outcomes are female gender, low socioeconomic status, and being unemployed. Even with appropriate treatment, though symptoms of fibromyalgia sometimes improve, the pain may get worse and continue for months or years.^[1]

If left untreated, chronic pain could cause permanent changes in how the body perceives pain.

Complications that can develop as a result of fibromyalgia are

• Marked functional impairment
• Depression
• Anxiety
• Insomnia
• Obesity
• Allodynia

• Fibromyalgia is a long-term disorder. Various factors play a key role in the outcomes. Several factors are associated with poor outcomes, including:
  • Female gender
  • Low socioeconomic status
  • Being unemployed

• Even with appropriate treatment, symptoms of fibromyalgia do not always improve. The pain may get worse and continue for months or years, though death by fibromyalgia is rare.

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