I. Definition
Doctors define a "syndrome" as a group of symptoms or other signs of disordered function that appear to be related to one another. By recognizing such clusters of symptoms, they are better able to identify people with similar symptoms in order to provide a common point of reference for research – as well as to provide a name (a diagnosis) to people for what ails them.
Thus, fibromyalgia is not a disease but a syndrome that causes chronic, widespread musculoskeletal pain, and that is often associated with one or more other symptoms, such as fatigue, stiffness, and insomnia. The pain of fibromyalgia syndrome (also known as FMS) typically includes particular areas of increased sensitivity called tender points. Such points are spots where application of mild finger pressure causes pain at that site – without spreading beyond that site.
Pain is difficult for anyone to describe or quantify. An accepted definition, from the International Association for the Study of Pain, is "...an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." The important point is that pain has both affective (or emotional) and sensory components and may occur in the absence of any obvious disease. In chronic pain such as that which occurs in FMS, the intensity of the pain response may seem out of proportion to the painful stimulus. Thus, just a mild poke at a tender point may produce what you feel as extreme physical pain.
Approximately 2% of the U.S. population meet the criteria for FMS that the American College of Rheumatology (ACR) established for research purposes. These criteria require patients to have widespread pain – both above and below the waist and on both sides of the body – for at least three months, in combination with a minimum of 11 of 18 specified tender points.
These ACR criteria define a group of patients with "definite fibromyalgia," which helps assure that patients included in clinical trials and other research groups all have a very similar cluster of symptoms. In actual clinical practice, however, physicians often diagnose as FMS patients who may not meet the rather rigid criteria of 11 or more tender points but, instead, who have a generalized lowering of the pain threshold along with other typical characteristics.
Despite the current poor understanding of its cause, FMS is commonly recognized in medical practice. An estimated four to seven million Americans are affected. FMS is more frequent and more severe in women, occurring in about 3.4% of women and 0.5% of men. Although it most commonly starts between the ages of 29 to 37 years, its prevalence increases with increasing age.
Until recently, FMS was often viewed as a predominantly psychiatric disorder, but clinical research has shown that the syndrome is not simply a manifestation of psychiatric morbidity (or illness). So – it's not all in your head. However, many physicians and other health care workers still do not agree on the validity of classifying fibromyalgia as a discrete clinical syndrome or on the relative contribution of psychological factors.
II. Pathogenesis
Pathogenesis refers to the origin and development of a disease. The fact that the cause of FMS remains unknown contributes greatly to continued misunderstanding and frustration on the part of patients and physicians. A yet-to-be-defined interplay of genetic and environmental factors leads to a process called "central sensitization" in fibromyalgia -- a sensitization of the central nervous system that is the proposed mechanism for pain amplification.
While the symptoms of FMS often develop gradually, up to one-quarter of patients cite a precipitant of physical or emotional trauma. Suggested (but not documented) environmental triggers include physical trauma, hypermobility (with repeated minor musculoskeletal trauma), infections, acute or chronic emotional distress, chronic underlying autoimmune disease, and others.
The contribution of psychological factors to development of FMS is still debated. A history of significant psychiatric disease correlates with more severe fibromyalgia. Concurrent depression is most common in patients treated at tertiary care referral centers, but it's not clear whether such depression precedes the FMS or is a result of the impact of FMS symptoms on daily life. Interestingly, post-traumatic stress disorder (PTSD) symptoms occur in half of patients with FMS, and these particular patients report greater pain, emotional distress and disability than those without PTSD.
Causative genetic factors have not been identified in FMS, although ongoing research is seeking possible susceptibility factors.
Current Theories
A significant number of biochemical and hormonal abnormalities have been identified in some people with FMS. In conjunction with electrophysiologic and functional neuro-imaging studies, they point toward basic neuro-endocrine abnormalities in FMS patients. While used in the study of disease pathophysiology, these findings are not currently useful in everyday diagnosis or care of the fibromyalgia patient. A brief review of such abnormalities follows.
Sleep abnormalities:
Insomnia is a frequent complaint of patients with fibromyalgia, and abnormalities are commonly documented on sleep electroencephalography (EEG), or brain wave monitoring. Up to 80% of patients show a characteristic pattern of abnormality with alpha wave intrusion into the normal delta rhythm of stage 4 (non-REM) sleep. Although not specific for FMS, this irregular sleep pattern may be an important factor contributing to the severity of symptoms. Muscle symptoms have been shown to develop in healthy subjects with experimentally interrupted sleep; such symptoms may relate to a resulting serotonin deficiency.
Endocrine factors:
Many patients have endocrine abnormalities that blunt the responses of their adrenal glands in certain situations. About a third of FMS patients have low levels of a hormone called insulin-like growth factor (IGF), resulting in decreased nocturnal growth hormone (GH) secretion. Again, measurements of these hormones are important in the study of the disease process but are not indicated for clinical use in patient care.
Metabolic abnormalities:
Several abnormalities in central nervous system fluid have been observed. These include increased levels of substance P (known to influence pain perception) and lowered levels of serotonin (known to influence both mood and pain perception). Evidence points to activation of receptors for "NMDA", a neurotransmitter known to be involved in increasing and maintaining chronic pain. Interestingly, the pain of fibromyalgia is blocked by intravenous dosing with ketamine – a short-acting substance that blocks the NMDA receptor in the brain.
Central Sensitization:
Fibromyalgia patients have qualitative differences in pain perception (with an overall increase in pain sensation) due to central sensitization, which causes a generalized disturbance in the processing of sensory information within the central nervous system. How might this occur?
Nociceptive (painful sensation) nerve fibers are those that normally carry painful signals to the brain. Repetitive stimulation of the pain-carrying peripheral nerve can lead to central sensitization through a mechanism called "wind-up" - a generalized up-regulation of the CNS, in which non-painful stimuli, or sensations, become perceived as pain. This may occur when nociceptive (painful) and non-nociceptive (non-painful) nerve endings converge on the same nerve cells in the spinal cord. Repetitive stimulation leads to "wind-up." As a result, FMS patients develop ongoing "non-nociceptive pain" (NNP) pain due to triggering of normally non-painful sensations, such as touch.
Neurophysiology studies support an enhanced or exaggerated pain response in patients with fibromyalgia, with increased EEG somatosensory responses to pain and abnormal spread of the impulse to the opposite cerebral cortex.
Functional abnormalities in brain blood flow (seen on brain imaging studies) are associated with low pain-threshold levels in fibromyalgia (in contrast to depression, for example, where such abnormalities are not seen). This occurs in areas of the brain that are important in the integration of painful stimuli and pain perception and in the generation of signals to other parts of the body.
The types of symptoms you have, your medical history, your age, and family history define the clinical presentation that your doctor observes. Diffuse musculoskeletal pain and tenderness are the clinical hallmarks of fibromyalgia. In general, muscle and skin symptoms predominate. While the sensation of joint swelling and pain is not uncommon, the doctor does not find objective evidence of joint inflammation.
Other common associated symptoms include fatigue, stiffness, skin tenderness, post-exertional pain, lightheadedness, fluid retention, insomnia, and paresthesias (sensations of numbness, tingling, or other heightened sensitivity). Stress or anxiety, lack of sleep, or cold exposure may make symptoms worse. Many people have cognitive problems, such as difficulty with memory and vocabulary. These problems are frequent and have been documented with formal testing in several studies.
No decisive data support a specific factor in a patient's medical history as a trigger for FMS, although it has been reported to follow numerous infections, including viral (hepatitis C, parvovirus) and bacterial (Lyme). Prior physical or emotional abuse has been associated with greater likelihood of various types of chronic pain in adulthood. Musculoskeletal injury as a precipitant is controversial. There is no evidence of an association of FMS with Gulf War service or silicone breast implants.
Associated syndromes are disorders which, while recognized as primary syndromes themselves, may overlap clinically with fibromyalgia and may reflect some manifestation of the same central sensitization process. These include: migraine, premenstrual syndrome, irritable bowel syndrome, restless leg syndrome, and Raynaud's syndrome. The degree of overlap may be significant; for example, one-third of patients with fibromyalgia also fulfill criteria for irritable bowel syndrome (IBS).
Despite the broad range of symptoms that patients may experience, the physical exam - except for tender points or other allodynia - is generally remarkably normal. (Allodynia is the term for the pain evoked by ordinarily non-painful stimuli.)
Laboratory tests in fibromyalgia are classically normal. Therefore they are not helpful in diagnosing or monitoring the syndrome. However, the following should be done to make sure you don't have any other disorders. These include: complete blood count (CBC), chemistries (including muscle enzyme tests CPK and aldolase), thyroid function tests, urinalysis, erythrocyte sedimentation rate (ESR), and a check of autoimmune blood markers such as antinuclear antibody (ANA) and rheumatoid factor (RF).
Many different diseases cause chronic pain. Differential diagnosis is the process by which the physician figures out which disorder is causing your problems. This is important because diseases that mimic FMS are often treated in a very different manner. Your physician will want to ensure an accurate diagnosis because the types of aggressive therapy used for other diseases that may have similar symptoms – such as lupus or rheumatoid arthritis (RA) – will not be helpful for FMS and can only expose you to potent drugs unnecessarily.
Patients with fibromyalgia – as with a small proportion of the general population – may occasionally have a low positive ANA or an elevated ESR test. This does not mean that the patient has systemic lupus or that his or her illness will develop into lupus. One guide to the diagnosis of fibromyalgia is duration of symptoms; it is less likely to be another disorder if symptoms have been present for many years.
People who have already been diagnosed with a connective tissue disorder also may develop fibromyalgia syndrome. FMS patients may have symptoms that are common in autoimmune disorders (such as systemic lupus erythematosus and rheumatoid arthritis); these include fatigue, arthralgia (joint achiness and/or pain), myalgia (muscle achiness and/or pain), morning stiffness, perception of joint swelling, malar flush (redness on the cheeks), and Raynaud's syndrome (painful sensations in the hands and feet upon exposure to cold). Identification of the correct underlying cause for particular symptoms in these patients may be difficult, especially when the patient has both fibromyalgia and a concomitant connective tissue disorder. Fibromyalgia may coexist with autoimmune disease in up to one-quarter of patients with systemic lupus and other connective tissue disorders. However, these other diseases have abnormal laboratory tests and/or other signs to differentiate them from FMS.
VI. Treatment
Treatment of fibromyalgia is management of a chronic illness. No cure exists. A combination of therapeutic modalities, however, may control symptoms for many patients. Therapies are best tailored to the needs and response of the individual patient because the patient population is diverse.
A. Medications
A limited number of medications have been shown to be effective for fibromyalgia in research that has compared the response to active drugs to that of placebos (inert pills). Traditional pain medications are often ineffective, and use of narcotic analgesics is discouraged. Research evidence of benefits is strongest for the use of certain antidepressants, specifically tricyclic antidepressant agents (TCAs), serotonin or serotonin/norepinephrine re-uptake inhibitors, and certain anticonvulsant drugs. Most studies, even with these agents, have been limited by a relatively short duration of follow-up. Although medications discussed below are FDA-approved, only Lyrica (pregabalin), Cymbalta (duloxetine), and Savella (milnacipran) are currently FDA-approved for use in fibromyalgia. You should understand that if you and your doctor decide that "off-label" use of another medication is appropriate for you.
It is important to understand that there are likely differences in pain processing between subgroups of patients with FMS which may influence response to drug therapy. For example, one research group treated FMS patients with separate intravenous infusions of morphine, lidocaine and ketamine – all potent painkillers. There was wide variation in clinical response between patients. So what helps another person may not help you. You and your doctor will have to work together to find what helps you best.
Prednisone (or other cortisone-like medication) is not indicated for therapy of fibromyalgia. It has been shown to be of no benefit in a double-blind crossover study.
Other promising pharmacologic agents include dopamine agonists (e.g. pramipexole), tizanidine, and even gamma-hydroxybutyrate (sodium oxabate). Other research agents currently under investigation include intravenous lidocaine and growth hormone. S-adenosyl-methionine (SAMe), a supplement available in health food stores, has been evaluated in several double-blind, randomized, controlled trials that have shown mixed results. Limitations include lack of conclusive benefit and the current limited availability of standardized preparations.
B. Non-pharmacologic therapies
The following non-pharmacologic therapies have been shown to be of benefit in several placebo-controlled trials.
C. Other alternative treatments
There are a number of less conventional approaches to treatment such as hypnotherapy, meditation, magnetic fields, EEG-driven stimulation, and dietary changes/manipulations. These have not been proven effective in reasonable clinical trials to date.
VII. Long term Management Issues
Long-term management issues in patients with fibromyalgia are difficult. As in most chronic illnesses for which no good therapy is yet available, frustration on the part of patient, family, and health care providers is common. Medications initially helpful may lose efficacy over time, and persistent adherence to exercise programs may be difficult. The most rational approach is to use a multi-faceted protocol including pharmacologic treatment, exercise, and behavioral therapies, along with education for the patient and his/her family.
One cannot underestimate the importance of reassurance and support for patients with fibromyalgia. Many patients fear a severe or fatal outcome due to the often frightening nature of symptoms. Reassurance involves emphasizing that fibromyalgia, even with severe pain, does not cause internal or "organ" involvement, and that the disease is unlikely to evolve into other illnesses whose symptoms FMS may mimic such as lupus, rheumatoid arthritis, or even multiple sclerosis. The goal is to help patients and family understand that fibromyalgia is a "real" clinical diagnosis, but one that is usually manageable and rarely leads to severe disability. Patient effort and social support are important in maintaining quality of life.
VIII. Prognosis
Prognosis seeks to forecast what your long-term experience with the disease is likely to be. Studies of long-term follow-up support the clinical impression that fibromyalgia is a chronic disease. In one study of patients with an average disease duration of 15 years, while most patients at follow-up still had fibromyalgia complaints, two-thirds of patients reported better than when first diagnosed. Less than 10% of patients felt they were doing poorly (see Kennedy below). Another longitudinal prospective study of shorter duration (see Fitzcharles et al. below) evaluated prognosis and specifically tried to identify factors that predicted a favorable outcome. While almost half the patients reported improvement in FMS status at 40 months follow-up, the only baseline predictors were younger age at onset and less disturbed sleep. Still, this adds impetus to the effort to diagnose patients as early as possible and is a reminder of the need to target sleep disturbance as part of overall disease management.
Periods of increased pain symptoms often alternate with periods of stable, less intense pain. It is uncommon for a patient to experience a complete, long-lasting remission of symptoms. When identified early, however, as many as a quarter of FMS patients in the community are reported to be in remission two years after diagnosis. Most patients with FMS who want to work are able to do so, although a proportion of patients change or modify their jobs as a result of their illness.
IX. When to Seek Referral to a Specialist
Often the primary care provider is the medical professional best suited to care for FMS patients, since he or she already knows the patients and may have an established relationship with them. However, referral to a specialist may be appropriate:
You may also want to seek referral if you feel that your physician is not providing you with the reassurance and support that you need to cope with the disease.
Referrals may vary, depending on patient symptoms, and specialists may play a role only in diagnosis. For example, paresthesias or complaints of muscle weakness may warrant evaluation of a patient by a neurologist to rule out a primary neurologic diagnosis. A rheumatologist will often be able to confidently rule out the diagnosis of lupus, rheumatoid arthritis, or other rheumatic disease.
If usual treatment fails, referral to a rheumatologist or other specialist for management is appropriate. The best care, however, will likely be with a team of specialists, including rheumatologists, physical therapists, psychologists, pain specialists, and others.
Other Resource:
http://www.fmaware.org/, official Web site of the National Fibromyalgia Association. An excellent site, with up to date and trustworthy information for patients and health professionals. They also have a monthly publication, the magazine Fibromyalgia Aware.
Updated: 12/30/2009
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