An In-Depth Overview of Fibromyalgia

1. Definition
2. Pathogenesis
3. Clinical Presentation
4. Laboratory Findings
5. Differential Diagnosis
6. Treatment
7. Long-term management issues
8. Prognosis
9. When to Seek Referral to a Specialist
10. Annotated Bibliography

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.

III. Clinical Presentation

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.)

IV. Laboratory Findings

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).

V. Differential Diagnosis

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.

1. The anticonvulsants pregabalin (Lyrica) and gabapentin (Neurontin) have both been recently shown to be effective in randomized controlled trials, and pregabalin is now FDA-approved for treatment of fibromyalgia. Both are generally well-tolerated by most patients; pregabalin is most effective at a total daily dose of 300-450 mg (usually in two or three doses), while gabapentin dose ranges from 1200-2400 mg daily (divided into 3 or 4 doses). Sedation is a concern with higher doses of both medications, and relatively larger doses are usually reserved for just prior to sleep. Alprazolam (Xanax) is the only benzodiazepine studied so far that has shown limited usefulness in fibromyalgia.
2. Serotonin/norepinephrine reuptake inhibitors include the antidepressants duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor). These medications are known to improve pain and function regardless of underlying depression. Milnacipran also binds specific receptors, which are thought to be important in chronic pain.
3. Tricyclic antidepressants (TCAs), specifically amitriptyline (Elavil), are probably the oldest type of drug therapy suggested to be effective for fibromyalgia. Use is limited, however, because many patients experience common side effects of dry eyes or mouth, drowsiness, and weight gain. The response rate for amitriptyline is about 30 to 50%. Improvement may be noted in pain relief, fatigue, and sleep quality. The usual dosage range is 10 to 50 mg, started at the lowest dose with incremental dose adjustment to minimize side effects.
4. Serotonin re-uptake inhibitors (SSRIs) represent another class of antidepressants felt to be potentially helpful for symptoms of fibromyalgia. Fluoxetine (Prozac) was shown to be of benefit in 60 patients with FMS in a 12-week placebo-controlled study. Improvement was independent of any effect on depressive symptoms. Study dose was flexible, from 10 to 80 mg per day; mean daily dose was 45 mg. Longer-term follow-up (beyond 12 weeks) was not reported.
5. Cyclobenzaprine (Flexeril), a common muscle relaxant, reduces brainstem noradrenergic function and motor neuron efferent activity, and is another commonly used medication with some proven benefit in fibromyalgia. Efficacy appears to decline with increasing duration of use, however, and sedating effects (even with the commonly used dose of 10 mg) often limit use to bedtime.
6. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are of debatable benefit in FMS patients, although most patients have been on NSAIDs at some point in their disease course. NSAIDs may have modest benefit in reducing pain in patients with FMS through analgesic rather than anti-inflammatory mechanisms.

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.

1. A regular exercise program is considered essential in the treatment of FMS. Aerobic exercise several times a week has clear benefit. Pool exercise may be particularly beneficial. Although pain may limit initial efforts, patients are encouraged to progress slowly through a program of increasing difficulty. Cardiovascular fitness training is superior to flexibility/stretching alone. The major problem encountered is poor compliance due to post-exertional pain and long-term dropout. Patients should be encouraged to persist in order to get past the early aches-and-pains that plague all formerly sedentary people who turn to exercise. A recent study confirmed the benefit of graded aerobic exercise by comparing one such 3-month program with a program of relaxation and flexibility exercises. More patients in the graded aerobic exercise group reported themselves much or very much better at three months (35% vs. 18%); most importantly, benefits were maintained at one year follow-up. Another study compared muscle strengthening with stretching alone, tailoring the individual program to the patient's baseline fibromyalgia status. While no statistically significant differences emerged between the two groups, there was a trend toward superiority of the muscle-strengthening protocol, and most patients in both groups completed the program without the post-exertional pain that often leads to high drop-out rates in exercise studies.
2. Cognitive-behavioral therapy (CBT), or behavior-modification therapy, is of proven benefit for patients with FMS. CBT teaches patients coping mechanisms to better deal with their chronic pain, and results in improved functional status. FMS patients may also respond to adjunctive psychological therapy, particularly those who clearly have depression as part of (or as a result of) their disorder.
3. Acupuncture is increasingly being used in pain management of many rheumatic diseases. A number of smaller studies previously suggested usefulness in FMS patients, and a recent blinded, controlled trial of FMS patients found that those receiving acupuncture improved in five out of eight outcome measures. A recent systematic review of acupuncture trials, however, concluded that there was inadequate evidence to support a recommendation for use in fibromyalgia.
4. Massage therapy is anecdotally helpful for many patients with fibromyalgia. One randomized trial comparing massage therapy with relaxation techniques found improvements in sleep and pain, and decreased levels of substance P. Comprehensive programs, available at a limited number of sites, include a combination of educational techniques, cognitive therapies, aerobic exercise, stretching, pacing, enhancement of pain tolerance, and family education. Significant improvement with any individual technique or combination of techniques, however, will not occur without the active participation of the patient.
5. In-patient programs, available at a very limited number of sites, include a combination of educational techniques, cognitive therapies, aerobic exercise, stretching, pacing, enhancement of pain tolerance, and family education. Significant improvement with any individual technique or combination of techniques, however, will not occur without the active participation of the patient.

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:

• when there is difficulty or uncertainty in establishing the diagnosis, or
• when the patient has an inadequate response to usual therapy.

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.

X. Annotated Bibliography

1. Russell IJ, Mease PJ, Smith TR et al. Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose clinical trial. Pain 2008;136:432-444. This was a 6-month multicenter study in which 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20mg/day, 60mg/day, or 120mg/day) or placebo, administered once daily, for 6 months. The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Study results demonstrated that duloxetine at doses of 60mg/day and 120mg/day was safe and efficacious in patients with fibromyalgia.
2. Crofford LJ, Rowbotham MD, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2005 Apr;52(4):1264-73. This multi-center trial randomized 529 patients to placebo or one of three doses of pregabalin (150, 300, or 450 mg/day) for a treatment period of 8 weeks. Pregabalin at 450 mg/day reduced pain, fatigue, and improved sleep quality and several domains of health-related quality of life. Pregabalin is the first FDA-approved treatment for fibromyalgia.
3. Mease PJ, Clauw DJ, Gendreau RM, et al. The efficacy and safety of milnacipran for treatment of fibromyalgia: a randomized, double-blind, placebo-controlled trial. J Rheumatol 2009;36:398-409. This was a 27-week multicenter study comparing milnacipran 100 and 200 mg/day with placebo in the treatment of 888 patients with FM. After 3-months, a significantly higher percentage of milnacipran-treated patients met criteria as FM responders versus placebo. A significantly higher percentage of patients treated with milnacipran 200 mg/day also met criteria as FM pain responders versus placebo (p = 0.032). Significant pain reductions were observed after Week 1 with both milnacipran doses. At 15 weeks, milnacipran 200 mg/day led to significant improvements over placebo in pain (realtime, daily and weekly recall; all measures, p < 0.05), fatigue (p = 0.016), cognition (p = 0.025), and other measured outcomes. Milnacipran was well tolerated by the majority of patients; nausea and headache were the most common adverse events. Milnacipran is safe and effective for the treatment of multiple symptoms of FM.
4. Arnold LM, Goldenberg DL, Stanford SB, et al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled multicenter trial. Arthritis Rheum 2007 Apr;56(4):1336-44. This 12-week trial involved 150 patients randomized to gabapentin or placebo; gabapentin-treated patients showed a significant improvement in BPI average pain severity score compared to placebo. Gabapentin dosage range was 1200 – 2400 mg per day.
5. Sarzi-Puttini P, Buskila D, Carrabba M, Doria A, Atzeni F. Treatment study in fibromyalgia syndrome: where are we now? Semin Arthritis Rheum 2008; 37(6):353-65. The authors review major developments in various areas of fibromyalgia research, including updates in clinical manifestations, pathophysiology and treatment. A limited number of well-controlled treatment trials of single agents were available for this review, but there are few trials of combination therapy (pharmacologic agent and either exercise or cognitive-behavioral therapy).
6. Kennedy M, Felson DT. A prospective long-term study of fibromyalgia syndrome. Arthritis Rheum. 1996 Apr;39(4):682-5. The authors reevaluated patients involved in a previous research study 10 years earlier. All patients had persistence of fibromyalgia symptoms, although half had not seen a doctor in the last year for them. Over two-thirds of patients were still taking medications for fibromyalgia. Two-thirds felt their fibromyalgia symptoms were a little or a lot better than at the time of diagnosis. With long-term follow-up, most patients were doing well 15 years out; only 7% felt they were doing poorly. A low rate of work disability was noted. One worrisome finding: two of the original 39 patients had since committed suicide. The authors caution to watch for depression in this disorder. Patients were enrolled from tertiary care (academic) medical institutions.
7. Mengshoel AM Haugen M. Health status in fibromyalgia -- a follow-up study. J Rheumatol. 2001 Sep;28(9):2085-9. This study is a long-term reevaluation of 33 women with fibromyalgia involved in exercise and patient education programs six to eight years earlier. All still had widespread pain, but 7 of 33 had fewer than 11 tender points (and wouldn't now "qualify" as having fibromyalgia by ACR criteria). No patient had additional disease. No worsening in symptoms was found. There was a significant reduction in fatigue. Seventy-six percent engaged in regular physical activity, and 30% in regular organized exercise classes. Employment status was unchanged. Patients used active coping strategies. The authors feel the data "suggest a benign prognosis." Of note, patients were originally recruited from primary care centers, in contrast to the study noted above.
8. Gedalia A, Garcia CO, Melin JF, Bradford MJ, Spinoza LR. Fibromyalgia syndrome: Experience in a pediatric rheumatology clinic. Clin Exp Rheumatol. 2000 May-Jun;18(3):415-9. Fibromyalgia occurs in all age groups. Here, 59 children and adolescents with fibromyalgia followed in a single pediatric rheumatology clinic are described. They had symptoms similar to those of adults, although stiffness, perception of joint swelling, and fatigue are slightly less common. At four years of follow-up, 60% children were improved, 36% were unchanged, and 4% were worse. Prognosis of fibromyalgia in children may be better than in adults, but longer term follow-up is needed. Exercise was associated with better outcome.
9. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990 Feb;33(2):160-72. The ACR committee developed classification criteria for fibromyalgia by studying 558 consecutive patients, 293 with fibromyalgia and 265 control patients. Control patients had disorders that could be confused with fibromyalgia, including inflammatory arthritis. Widespread pain as defined by the committee was found in 97.6% fibromyalgia patients. The criteria of widespread pain plus tender points had an overall sensitivity 88.4% and specificity of 81.1%. This landmark report provided much-needed classification criteria for studies, as well as an ACR validation of fibromyalgia as a distinct clinical diagnosis.
10. Park DC, Glass JM, Minear M, Crofford LJ. Cognitive function in fibromyalgia patients. Arthritis Rheum. 2001 Sep;44(9):2125-33. This study documents cognitive impairment in fibromyalgia patients (in areas of memory and vocabulary) when compared with two groups of controls. Cognitive deficits in fibromyalgia are not global. Impaired cognition correlates with pain but not with depressive or anxiety symptoms. Deficits are similar to those seen in aging; however, speed of processing is not impaired in fibromyalgia patients. Complaints of FM patients about their memory are legitimate and are not due to psychological distress.
11. Hadhazy VA, Ezzo J, Creamier P, Berman B. Mind-body therapies for the treatment of fibromyalgia. A systematic review. J Rheumatol. 2000 Dec;27(12):2911-8. This is a systematic review of randomized and "quasi-randomized" trials of mind-body therapy (MBT) for fibromyalgia. Thirteen trials included a total of 802 subjects who were compared to waiting list or treatment-as-usual controls. The analysis provided strong evidence that MBT is more effective for improving self-efficacy than are other therapies. There is limited evidence for improved quality of life with MBT. Results were inconclusive for other outcomes. Overall, the authors feel that long-term within-group results show the greatest benefit for MBT in combination with exercise. This defines a focus for further controlled clinical research.
12. Al-Allaf AW, Ottewell L, Pullar T. The prevalence and significance of positive antinuclear antibodies in patients with fibromyalgia syndrome: 2-4 years' follow-up. Clinical Rheumatology 2002 Nov;21(6):472-477. A large rheumatology clinic population of patients with fibromyalgia (n=137) was screened for ANA antibodies: 12 ANA-positive patients were identified and matched for age and sex with 12 ANA-negative fibromyalgia patients; a further control group of osteoarthritis patients was also studied. Prevalence of symptoms of connective tissue disease was similar in both the ANA-positive and ANA-negative fibromyalgia groups and the ANA-positive osteoarthritis group. Two of 137 patients with fibromyalgia (one ANA-positive and one ANA-negative) fulfilled criteria for a connective tissue disease (CTD): lupus and Sjogren's syndrome respectively. One ANA-positive patient (of 225) in the osteoarthritis control group was diagnosed with rheumatoid arthritis. New diagnoses of CTD did not develop over the 2-4 year follow-up period.
13. Richards SC, Scott DL. Prescribed exercise in people with fibromyalgia: parallel group randomized controlled trial. British Med J 2002:325:185. This recent study confirmed the benefit of graded aerobic exercise by comparing a prescribed graded aerobic exercise program with one of relaxation and flexibility exercises. More patients in the graded aerobic exercise group reported themselves much or very much better at three months (35% vs. 18%) with a reduction in tender point count and improvement in score on the Fibromyalgia Impact Questionnaire, or FIQ (a functional assessment instrument validated specifically for patients with fibromyalgia). Most importantly, benefits were still demonstrated at a one-year follow-up evaluation, a relatively long period of follow-up for any study of fibromyalgia therapies.
14. Jones KD, Burckhardt CS, Clark SR, et al. A randomized controlled trial of muscle strengthening versus flexibility training in fibromyalgia. J Rheumatol 2002;29:1041- 1048. Muscle-strengthening was shown to be superior to flexibility exercise alone in this controlled trial, which tailored the individual exercise program to the patient's baseline fibromyalgia status. While no statistically significant differences emerged between the two groups, there was a trend toward superiority of the muscle-strengthening protocol, and most patients in both groups completed the program without the post-exertional pain that often leads to high drop-out rates, a common problem for patients with fibromyalgia.
15. Fitzcharles MA, Costa DD, Poyhia R. A study of standard care in fibromyalgia syndrome: a favorable outcome. J Rheumatol 2003 Jan;30(1):154-159. A longitudinal prospective cohort study at the Montreal General Hospital in Canada to evaluate outcome of standard medical care and to identify factors that might predict or influence outcome. Seventy women with fibromyalgia were followed for a mean of 40 months while under the care of their usual physicians. Primary outcome was determined by patient-reported overall status, secondary outcomes included measures of pain and fatigue on standardized instruments, HAQ (Health Assessment Questionnaire) and FIQ (Fibromyalgia Impact Questionnaire). Forty-seven percent of patients reported an overall moderate to marked improvement in disease status, with significant differences seen in tender point count, sleep disturbance, fatigue, pain, and score on FIQ. Age and lower sleep disturbance were the only variables linked to favorable outcome.

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

Authors

Lisa R. Sammaritano, MD
Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medicine