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| ICD9 = | ICDO = | OMIM = | MedlinePlus = 000427 | eMedicineSubj = med | eMedicineTopic = 790 | eMedicine_mult = | MeshID = D005356Fibromyalgia (FM or FMS) is a chronic syndrome (constellation of signs and symptoms) characterized by diffuse or specific muscle, joint, or bone pain, fatigue, and a wide range of other symptoms. It is not contagious, and recent studies suggest that people with fibromyalgia may be genetically predisposed. It affects more females than males, with a ratio of 9:1 by ACR (American College of Rheumatology) criteria.Fibromyalgia Fibromyalgia is seen in 3% to 6% of the general population. Recently there has been an increase in the number of diagnoses, which is assumed to be associated with better identification of the disorder. It is most commonly diagnosed in individuals between the ages of 20 and 50, though onset can occur in childhood. The disease 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 syndrome is generally perceived as non-progressive.
History Fibromyalgia has been studied since the early 1800s and referred to by a variety of former names, including muscular rheumatism and fibrositis. The term fibromyalgia was coined in 1976 to more accurately describe the symptoms, from the Latin fibra (fiber)Meaning of fibra and the Greek words myo (muscle)Meaning of myo and algos (pain).Meaning of algosFibromyalgia was first recognized by the American Medical Association as an illness and a cause of disability in 1987. In an article the same year, in the Journal of the American Medical Association, a physician named Dr. Don Goldenberg called the syndrome Fibromyalgia.
Symptoms The defining symptoms of fibromyalgia are chronic, widespread pain and tenderness to light touch, and usually moderate to severe fatigue. Those affected may also experience heightened sensitivity of the skin (also called allodynia), tingling of the skin (often needle-like), achiness in the muscle tissues, prolonged muscle spasms, weakness in the limbs, and nerve pain. Chronic sleep disturbances are also characteristic of fibromyalgia -- and not just from discomfort: some studies suggest that these sleep disturbances are the result of a sleep disorder called alpha-delta sleep, a condition in which deep sleep (associated with delta EEG waves) is frequently interrupted by bursts of brain activity similar to wakefulness (i.e. alpha waves). Deeper stages of sleep (stages 3 & 4) are often dramatically reduced.In addition, many patients experience cognitive dysfunction (known as "brain fog" or "fibrofog"), which may be characterized by impaired concentration and short-term memory consolidation, impaired speed of performance, inability to multi-task, and cognitive overload. Many experts suspect that "brain fog" is directly related to the sleep disturbances experienced by sufferers of fibromyalgia. However, the relationship has not been strictly established.Other symptoms often attributed to fibromyalgia (possibly due to another comorbid disorder) may include myofascial pain syndrome, chronic paresthesia, physical fatigue, irritable bowel syndrome, genitourinary symptoms (such as those associated with the chronic bladder condition interstitial cystitis), dermatological disorders, headaches, myoclonic twitches, and symptomatic hypoglycemia. Although it is common in people with fibromyalgia for pain to be widespread, it may also be localized in areas such as the shoulders, neck, back, hips, or other areas. Many sufferers also experience varying degrees of temporomandibular joint disorder. Not all patients have all symptoms.Symptoms can have a slow onset, and many patients have mild symptoms beginning in childhood, that are often misdiagnosed as growing pains. Symptoms are often aggravated by unrelated illness or changes in the weather. They can become more tolerable or less tolerable throughout daily or yearly cycles; however, many people with fibromyalgia find that, at least some of the time, the condition prevents them from performing normal activities such as driving a car or walking up stairs. The syndrome does not cause the inflammation as is present in rheumatoid arthritis, although some NSAIDs may temporarily reduce pain symptoms in some patients. Their use however is limited, and often of little to no value in pain management.
Variability of symptomsThe following factors have been proposed to exacerbate symptoms of pain in patients:
Proposed causes and pathophysiology The cause of fibromyalgia is still unknown. Fibromyalgia can, but does not always, start as a result of some trauma such as a traffic accident, major surgery, or disease. Some evidence shows that Lyme Disease may be a trigger of fibromyalgia symptoms. Another study suggests that more than one clinical entity may be involved, ranging from a mild, idiopathic inflammatory process to clinical depressionhttp://www.springerlink.com/content/1271314042w8405g/ Mueller W, et al. The classification of fibromyalgia syndrome. Rheumatol Int. 2007 Jul 25
GeneticsUsing self-report of "Chronic Widespread Pain" (CWP) as a surrogate marker for fibromyalgia, the Swedish Twin Registry suggests a modest genetic contribution:
StressStudies have shown that stress is a significant precipitating factor in the development of fibromyalgia, and that PTSD is linked with fibromyalgia. The Amital study found that 49% of PTSD patients fulfilled the criteria for FMS, compared with none of the controls.Related to this is the idea that fibromyalgia may be a psychosomatic illness. One controversial theory of this nature has been popularized in the books of Dr. John E. Sarno, as a theoretical condition to which Dr. Sarno has given the name of "tension myositis syndrome". Dr. Sarno's theory claims that in many cases chronic pain is the result of physical changes in the body caused by a person's subconscious as a strategy for distracting from painful or dangerous unconscious emotions, such as repressed anger. Dr. Sarno believes that this can be treated through a program of education and attitude change (and in some cases, psychotherapy) which stops the brain from using that chronic pain strategy.
Dopamine abnormalityDopamine is a neurotransmitter that is known to play a role in the pathogenesis of Parkinson's disease as well as restless leg syndrome. It has been proposed that fibromyalgia represents a hypodopaminergic state that likely results from a combination of genetic predisposition and exposure to environmental stressors, including inflammatory disorders (e.g. rheumatoid arthritis, systemic lupus erythematousus), systemic viral infections or psychosocial distress. In support of this proposition, a reduction in dopamine synthesis was demonstrated by a study that used positron emission tomography (PET) and demonstrated a reduction in dopamine synthesis in several brain regions in which dopamine plays a role in inhibiting pain perception. http://www.ncbi.nlm.nih.gov/pubmed/17023218?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum A subsequent PET study demonstrated that fibromyalgia patients fail to release dopamine in response to a tonic experimental pain stimulus. http://www.ncbi.nlm.nih.gov/pubmed/17610577?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Pramipexole is a drug that stimulates dopamine D2/D3 receptors and is used to treat both Parkinson's disease and restless legs syndrome. It has also been shown in controlled trials to have a positive effect on fibromyalgia.
SerotoninSerotonin is a neurotransmitter that is known to play a role in regulating sleep patterns, mood, feelings of well-being, concentration, digestion. One hypothesis for the pathophysiology of fibromyalgia is a dysregulation of serotonin and norepinephrine in the neural synapse, contributing to many associated fibromyalgia symptoms.The drug Cymbalta, originally used to treat depression, has been used successfully in treating fibromyalgia off-label. Cymbalta has not been approved by the FDA for fibromyalgia.On October 19 2006, Eli Lilly issued a press release stating they had done trials which found Cymbalta, 60 mg once or twice daily, significantly reduced pain in more than half of women treated for fibromyalgia (FM), with and without major depression, according to 12-week data presented at the annual meeting of the American College of Rheumatology. Eli Lilly is in Phase III of its FM trials and is expected to submit a supplementary new drug application (sNDA) to the FDA for approval of Cymbalta for FM within the next 12 months.Critics argue that randomized controlled trials of FM are difficult due to factors such as a lack of understanding of the pathophysiology and a heterogeneous FM patient population. Although there is a lack of understanding of what causes FM, it is estimated that approximately 5-7% of the U.S. population has FM, representing a large patient clientèle. Eli Lilly hopes Cymbalta will be the first FDA approved medication for FM and had been promoting Cymbalta for FM since 2004.In the study testing the efficacy of Cymbalta for FM, participants completed several questionnaires to measure the amount of pain and discomfort the disease caused them at the beginning of the study, and then at the end of each of the first two weeks and every second week for the remaining 12 weeks of the study. Researchers also tested the participants for depression.Women who took Cymbalta had significantly less pain and discomfort than those who took the placebo. For men, who made up only 11 percent of the study, there was no effect from taking the medication compared with a placebo. Reportedly, depression played no part in whether or not the drug worked to control pain. The change in the level of women's pain was particularly pronounced after a month of taking the drug, then levelled off a bit before dropping again near the end of the study.However, in one of the primary measures of pain there was no significant difference between the two groups at the end of the 12-week trial. Also, because the trial lasted only 12 weeks, it is impossible to tell how well the drug would control treatment for a longer period of time. Lastly, the primary researcher on the project has received more than $10,000 in consulting fees from Eli Lilly, the manufacturer of Cymbalta, all other researchers also had ties to the company, reflecting a conflict of interest.
Sleep disturbanceElectroencephalography studies have shown that people with fibromyalgia lack of 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. According to the sleep disturbance theory, an event such as a trauma or illness causes sleep disturbance and possibly initial chronic pain that may initiate the disorder. The theory supposes that stage 4 sleep is critical to the function of the nervous system, as it is during that stage that certain neurochemical processes in the body 'reset'. In particular, pain causes the release of the neuropeptide substance P in the spinal cord which has the effect of amplifying pain and causing nerves near the initiating ones to become more sensitive to pain. Under normal circumstances, areas around a wound to become more sensitive to pain but if pain becomes chronic and body-wide this process can run out of control. The sleep disturbance theory holds that deep sleep is critical to reset the substance P mechanism and prevent this out-of-control effect.The sleep disturbance/substance P theory 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 theory posits 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 theory 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 theory could also provide 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, and thus injury or imbalance in this area could cause both CFS and sleep-related fibromyalgia.Critics of the theory argue that it does not explain slow-onset fibromyalgia, fibromyalgia present without tender points, or patients without heightened pain symptoms, and a number of the non-pain symptoms present in the disorder.
Human growth hormoneAn alternate theory suggests that stress-induced problems in the hypothalamus may lead to reduced sleep and reduced production of human growth hormone (HGH) during slow-wave sleep. People with fibromyalgia tend to produce inadequate levels of HGH. Most patients with FM with low IGF-I levels failed to secrete HGH after stimulation with clonidine and l-dopa.This view is supported by the fact that those 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 though there is disagreement about the theory.
Deposition diseaseAnother theory involves phosphate and calcium accumulation in cells that eventually reaches a level to impede the ATP process, possibly caused by a kidney defect or missing enzyme that prevents the removal of excess phosphates from the blood stream. This theory posits that fibromyalgia is an inherited disorder, and that phosphate build-up 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 prods the cell to continue producing ATP. - sets out Dr St Amand's theoryDiagnosis is made with a specialized technique called mapping, a gentle palpitation of the muscles to detect lumps and areas of spasm that are thought to be caused by an excess of calcium in the cytosol of the cells. This mapping approach is specific to deposition theory, and is not related to the trigger points of myofascial pain syndrome.While this theory does not identify the causative mechanism in the kidneys, it proposes a treatment known as guaifenesin therapy. This treatment involves administering the drug guaifenesin to a patient's individual dosage, avoiding salicylic acid in medications or on the skin, and, if the patient is also hypoglycemic, a diet designed to keep insulin levels low.The phosphate build-up theory explains many of the symptoms present in fibromyalgia and proposes an underlying cause. The guaifenesin treatment, based on this theory, has received mixed reviews, with some practitioners claiming many near-universal successes and others reporting no success. Only one controlled clinical trial has been conducted to date, and it showed no evidence of the efficacy of this treatment protocol. This study was criticized for not limiting the salicylic acid exposure in patients, and for studying the effectiveness of only guaifenesin, not the entire treatment method. As of 2005, further studies to test the protocol's effectiveness are in the planning stages, with funding for independent studies largely collected from groups which advocate the theory. It should be noted that nothing in the scientific literature supports the proposition that fibromyalgia patients have excessive levels of phosphate in their tissues.
Other hypothesesOther theories relate to various toxins from the patient's environment, viral causes such as the Epstein-Barr Virus, growth hormone deficiencies possibly related to an underlying (maybe 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. A 2001 study suggested an increase in fibromyalgia among women with extracapsular silicone gel leakage, compared to women whose implants were not broken or leaking outside the capsule. This association has not repeated in a number of related studies, and the US-FDA concluded "the weight of the epidemiological evidence published in the literature does not support an association between fibromyalgia and breast implants." Due to the multi-systemic nature of illnesses such as fibromyalgia and chronic fatigue syndrome (CFS/ME), an emerging branch of medical science called psychoneuroimmunology (PNI) is looking into how the various theories fit together.Another hypothesis on the cause of symptoms in Fibromyalgia states that patients suffer from vasomotor dysregulation causing improper vascularflow and hypoperfusion (decreased blood flow to a given tissue or organ).
Always a comorbid disease?Cutting across several of the above hypotheses is a hypothesis that proposes that fibromyalgia is almost always a comorbid disorder, occurring in combination with some other disorder that likely served to "trigger" the fibromyalgia in the first place. Two possible triggers are gluten sensitivity and/or irritable bowel. Irritable bowel is found at high frequency in fibromyalgia, and a large coeliac support group survey of adult celiacs revealed that 7% had fibromyalgia and also has a co-occurrence with chronic fatique. By this hypothesis, some other disorder (or trauma) occurs first, and fibromyalgia follows as a result. In some cases, the original disorder abates on its own or is separately treated and cured, but the fibromyalgia remains. This is especially apparent when fibromyalgia seems triggered by major surgery. In other cases the two disorders coexist.
Diagnosis There is still debate over what should be considered essential diagnostic criteria. The most widely accepted set of classification criteria for research purposes were elaborated in 1990 by the Multicenter Criteria Committee of the the American College of Rheumatology. These criteria, which are known informally as "the ACR 1990" define fibromyalgia according to the presence of the following criteria:
DifferentialsA number of other disorders can produce similar symptoms to fibromyalgia:
Treatment As with many other syndromes, there is no universally accepted cure for fibromyalgia, though some physicians claim to have found cures. However, a steady interest in the syndrome on the part of academic researchers as well as pharmaceutical interests has led to improvements in its treatment, which ranges from symptomatic prescription medication to alternative and complementary medicine.
MedicationsMost medications are used to treat specific symptoms of fibromyalgia, such as muscle pain and insomnia.
Muscle RelaxantsMuscle relaxants, such as cyclobenzaprine or tizanidine, may be used to treat the muscle pain associated with the disorder.http://www.webmd.com/fibromyalgia/Cyclobenzaprine-hydrochloride-for-fibromyalgia http://www.fibromyalgia-reviews.com/Drg_Zanaflex.cfmhttp://www.intelihealth.com/IH/ihtIH/WSIHW000/8310/8310.html
Tricyclic antidepressants (TCAs)Traditionally, low doses of sedating antidepressants (e.g. amitriptyline and trazodone) have been used to reduce the sleep disturbances that are associated with fibromyalgia and are believed by some practitioners to alleviate the symptoms of the disorder. Because depression often accompanies chronic illness, these antidepressants may provide additional benefits to patients suffering from depression. Amitriptyline is often favoured as it can also have the effect of providing relief from neuralgenic or neuropathic pain. It is to be noted that Fibromyalgia is not considered a depressive disorder; antidepressants are used for their sedating effect to aid in sleep.
Selective serotonin reuptake inhibitors (SSRIs)Standard clinical doses of newer anti-depressants (SSRIs) like Citalopram (Celexa) have demonstrated good efficacy in some cases of fibromyalgia.
Anti-seizure drugsAnti-seizure drugs are also sometimes used, such as gabapentin and pregabalin (Lyrica). Pregabalin, originally used for the nerve pain suffered by diabetics, has been approved by the American Food and Drug Administration for treatment of fibromyalgia. A randomized controlled trial of pregabalin 450 mg/day found that a number needed to treat of 6 patients for one patient to have 50% reduction in pain.
Dopamine agonistsDopamine agonists, such as Mirapex, are now being studied and used to treat fibromyalgia.
Combination therapyAmitriptyline and fluoxetine can be combined according to a randomized crossover study.
Cannabis and cannabinoidsFibromyalgia patients frequently self-report using cannabis therapeutically to treat symptoms of the disease. Writing in the July 2006 issue of the journal Current Medical Research and Opinion, investigators at Germany's University of Heidelberg evaluated the analgesic effects of oral THC (∆9-tetrahydrocannabinol) in nine patients with fibromyalgia over a 3-month period. Subjects in the trial were administered daily doses of 2.5 to 15 mg of THC, but received no other pain medication during the trial. Among those participants who completed the trial, all reported a significant reduction in daily recorded pain and electronically induced pain. Previous clinical and preclinical trials have shown that both naturally occurring and endogenous cannabinoids hold analgesic qualities, particularly in the treatment of cancer pain and neuropathic pain, both of which are poorly treated by conventional opioids. As a result, some experts have suggested that cannabinoid agonists would be applicable for the treatment of chronic pain conditions unresponsive to opioid analgesics such as fibromyalgia, and they theorize that the disease may be associated with an underlying clinical deficiency of the endocannabinoid system.
GuaifenesinBecause of its uricosuric effect, guaifenesin (Guai) was chosen for the experimental guaifenesin protocol in the 1990s as a treatment for fibromyalgia, and proponents of the guaifenesin protocol believe that it cures fibromyalgia by removing excess phosphate from the body. A lesser publicized and thus lesser known fact among fibromyalgia sufferers is that guaifenesin has a skeletal muscle relaxant property, and a form of guaifenesin known as guafenesin carbomate is used for this purpose.needed This may explain some of the symptomatic relief experienced by fibromyalgia sufferers who take guaifenesin. This method of treatment was pioneered by Dr. R. Paul St. Amand of Los Angeles, California and there is a great deal of reported success amongst patients recieving it. During the course of the patient taking Guai, he or she will experience what is known as "cycling", periods of reduced symptoms, followed by periods of more noticable symptoms. Over the course of medication, these periods become further apart and the period of increased symptoms, less noticable. It is noteworthy that the benficial effects of Guai are mitigated by contact with and absorption of salicylates, found in many of plants and their products which in even tiny amounts blocks guaifenesin from binding in the kidneys. It is present in many drugs such as aspirin, Salsalate, Disalcid, Anacin, and Excedrin. Plants produce salicylic acid, so herbal medications must be avoided as well as plant oils, gels and extracts in cosmetics and any product that touches the skin. These ingredients include aloe, castor oil, camphor, and mint. Any plants can be eaten, however, because the small amount of salicylic acid present in food is broken down in the digestive system and tagged with glycine by the liver before reaching the kidneys.For further information see Guaifenesin protocol.
Homeopathic RemediesUsers of Epsom Salts in the gel form (Magnesium Sulfate), have reported significant and lasting relief from pain associated with fibromyalgia. Epsom Salts have long been touted for its ability to reduce pain and swelling. Epsom Salts Industry Council [http://www.epsomsaltcouncil.org/health_why_it_works.htm]
Physical treatmentsStudies have found exercise improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia. Many patients find temporary relief by applying heat to painful areas. Those with access to physical therapy, massage, acupuncture may find them beneficial. Most patients find exercise, even low intensity exercise to be extremely helpful. Osteopathic manipulative therapy can also temporarily relieve pain due to fibromyalgia.A holistic approach—including managing diet, sleep, stress, activity, and pain—is used by many patients. Dietary supplements, massage, chiropractic care, managing blood sugar levels, and avoiding known triggers when possible means living as well as it is in the patient's power to do.
Psychological/Behavioral TherapiesAs the nature of fibromyalgia is not well understood, some physicians believe that it may be psychosomatic or psychogenic. Although there is no universally accepted cure, some doctors have claimed to have successfully treated fibromyalgia when a psychological cause is accepted.Cognitive behavioral therapy has been shown to improve quality of life and coping in fibromyalgia patients and other sufferers of chronic pain.Chakabarty, S. & Zoorob, R. (2007). Fibromyalgia. American Family Phisician, 76, 2, pp. 247-254. Neurofeedback has also shown to provide temporary and long-term relief.Treatment for the "brain fog" has not yet been developed, however biofeedback and self-management techniques such as pacing and stress management may be helpful for some patients. The use of medication to improve sleep helps some patients, as does supplementation with folic acid and ginkgo biloba.
Dietary treatmentIn a 2001 review of four case studies, symptom alleviation was found by minimising consumption of sodium glutamate.Smith et al, Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins, Ann Pharmacother. 2001 Jun;35(6):702-6.
Investigational treatmentsMilnacipran, a member of the new series of drugs known as serotonin-norepinephrine reuptake inhibitors (SNRIs), is available in parts of Europe where it has been safely prescribed for other disorders. On May 22nd, 2007, a Phase III study demonstrated statistically significant therapeutic effects of Milnacipran as a treatment of fibromyalgia syndrome. At this time, only initial top-line results are available and further analyses will be completed in the coming weeks. If ultimately approved by the FDA, Milnacipran could be distributed in the United States as early as summer, 2008.Among the more controversial therapies involves the use of guaifenesin; called St. Amand's protocol or the guaifenesin protocol the efficacy of guaifenesin in treating fibromyalgia has not been proven in properly designed research studies. Indeed, a controlled study conducted by researchers at Oregon Health Science University in Portland failed to demonstrate any benefits from this treatment, though these results have been contested.Another drug being researched is the use of dextromethorphan, which is sold over the counter as a cough suppressant.
Living with fibromyalgia Fibromyalgia can affect every aspect of a person's life. While neither degenerative nor fatal, the chronic pain associated with fibromyalgia is pervasive and persistent. FMS can severely curtail social activity and recreation, and as many as 30% of those diagnosed with fibromyalgia are unable to maintain full-time employment. Like others with disabilities, individuals with FMS often need accommodations to fully participate in their education or remain active in their careers.In the United States, those who are unable to maintain a full-time job due to the condition may apply for Social Security Disability benefits. Although fibromyalgia has been recognized as a genuine, severe medical condition by the government, applicants are often denied benefits, since there are no formal diagnostic criteria or medically provable symptoms. Because of this, if an applicant does have a medically verifiable condition that would justify disability benefits in addition to fibromyalgia, it is recommended that they not list fibromyalgia in their claim. However, most are awarded benefits at the judicial level; the entire process often takes two to four years. In the United Kingdom, the Department for Work and Pensions recognizes fibromyalgia as a condition for the purpose of claiming benefits and assistance.The Fibromyalgia Association of the UKFibromyalgia is often referred to as an "invisible" illness or disability due to the fact that generally there are no outward indications of the illness or its resulting disabilities. The invisible nature of the illness, as well as its relative rarity and the lack of understanding about its pathology, often has psychosocial complications for those that have the syndrome. Individuals suffering from invisible illnesses in general often face disbelief or accusations of malingering or laziness from others that are unfamiliar with the syndrome.There are a variety of support groups on the Web that cater to fibromyalgia sufferers.
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