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CMEEarn Category I CME credit by reading this article and "Strep throat: Guidelines for diagnosis and treatment" and successfully completing the post-test. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of September 2005.
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Fibromyalgia syndrome (FMS) is characterized as chronic, widespread musculoskeletal pain accompanied by fatigue and several tender points on examination (see Figure 1).1 A form of soft tissue rheumatism causing pain and stiffness around joints as well as in muscles and bones, FMS is not associated with arthritis, inflammation, or musculoskeletal or degenerative disorders.2 Associated symptoms may include sleep disturbance, anxiety, depression, headaches, and irritable bowel syndrome (IBS).3
Fibromyalgia was first described as fibrositis in mid-19th century Europe.4 The American College of Rheumatology established criteria for diagnosing FMS in 1990 (see Table 1).5 Diagnosis is less controversial than it was before guidelines were established, although providing the best management remains a burden for many practitioners. No specific, objective data can be used to diagnose FMS, but such information can be used to exclude other conditions or recognize comorbid disorders.2 A thorough history and physical examination are essential, with a focus on widespread pain lasting longer than 3 months along with pain in at least 11 of 18 specified tender points. These criteria are effective in distinguishing FMS from other rheumatic and chronic pain conditions.5,6
The prevalence of FMS is thought to be 2% in the general population, 5% in primary care, and 10% to 20% in rheumatology clinics.7 FMS typically develops in women aged 30 to 55 years. Prevalence increases from approximately 2% at age 30 years to 7.4% at age 70 years.7 FMS occurs more frequently among relatives of patients who have FMS, as do related conditions, such as IBS, migraine, and mood disorders.8,9
The specific cause of FMS has not been determined, although it often occurs after certain stressors or triggers. There is a correlation between the onset of FMS and triggers such as Lyme disease, hypothyroidism, viral infections, and autoimmune disorders.9 There are also associations between FMS and physical or emotional trauma10 and between tender points and childhood abuse.11 An estimated 53% to 65% of women with FMS were abused as children.12 A number of patients have low levels of serotonin and norepinephrine, high levels of substance P, abnormalities in imipramine uptake receptors, and neurohormonal disturbances including low levels of growth hormone and hypothalamic-pituitary-adrenal axis hypofunction.13
Most recently, evidence has pointed toward a state of central hyperexcitability and abnormal sensory processing in nociception and less toward psychological factors.14,15 Patients with FMS have lower pain thresholds and increased sensitivity to pressure and thermal stimuli compared to controls, suggesting a central neurobiological mechanism of increased pain sensitivity.16 Gracely and colleagues used functional MRI scans to demonstrate that the pain felt by FMS patients is real.17
Patients also have high lifetime rates of comorbid conditions such as headaches, IBS, chronic fatigue syndrome (CFS), temporomandibular disorder (TMD), major depressive disorder (MDD), and panic disorder.18 Seventy-five percent of patients with fibromyalgia do not have active depression, supporting the belief that FMS is not caused by psychological distress, although there may be a common pathway.3
FMS, CFS, and TMD may also be linked; these conditions share symptoms of myalgia, headaches, IBS, fatigue, chemical sensitivities, and decreased ability to perform activities of daily living.18 The diagnostic criteria for FMS and CFS are similar, making differentiation difficult (see Table 2). Because almost 70% of patients with FMS meet the diagnostic criteria for CFS,18 and because the majority of patients with CFS meet the tender point criteria for FMS,20 treatment is often similar and targeted for both FMS and CFS.
A thorough history and physical examination, including the tender point assessment, are generally all that are necessary to diagnose FMS. A few carefully selected laboratory tests may aid the differential diagnosis.
During the history, ask about sleep disturbance, fatigue, and morning stiffness, which are signature symptoms of FMS.5 A majority of patients also have diffuse pain, morning fatigue, headache, paresthesias, depression, anxiety, and what they describe as “pain all over.”19 Areas often emphasized are the neck, shoulders, low back, and hips. Other common symptoms are IBS, joint pain, restless legs, cognitive difficulties such as memory loss, tender muscle and tendon insertion sites, and the inability to localize the pain. Patients may report decreased exercise tolerance or avoid exercise because their pain is increased afterward (see Table 3). Clinicians should screen for depression and inquire about a past personal or family history of psychological disorders and chronic musculoskeletal pain.
On physical examination, there should be no sign of inflammation or muscle weakness. Findings 
should be normal except for pain caused by pressure at tender points. The correct amount of applied pressure to tender points is 4 kg/cm, which is just enough to blanch
the nail bed of the examiner’s finger. The patient, who should find this more painful than tender, may experience other signs of allodynia during the examination because patients with FMS have lower pain thresholds.
Other diagnoses to consider are listed in Table 4. Avoid unnecessary diagnostic procedures by taking a good history and performing a physical examination. Although test results are often normal in patients with fibromyalgia, a CBC, ESR, thyroid profile, and standard chemistry panel can help to rule out systemic illness.23 Since there is a high rate of false-positive results on tests for antinuclear antibodies and rheumatoid factor, use them only if the history and examination suggest they will be helpful.
The patient with FMS has probably had it for years, consulted different specialists, tried several 
treatments, and felt stymied and frustrated. Patient education and self-management are essential in the initial treatment of FMS, but it is important to point patients toward reliable information (see “Patient Resources”). Reassure them that their illness is not imaginary, infectious, life threatening, or likely to worsen. Although symptoms may be chronic, most people with FMS can go on to lead active and normal lives.
Explain the roles that fatigue, depression, exercise, self-management, and social support play in FMS. Patients may feel less frustrated if they know symptoms can improve with medication for sleep disturbances and depression, aerobic exercise to improve blood flow to muscles and prevent deconditioning, and psychiatric interventions such as cognitive behavior therapy (CBT) to help them handle pain.
No drugs have been FDA approved to treat FMS, but two thirds of patients are currently taking medication.7 Drugs often prescribed include tricyclic antidepressants (TCAs), muscle relaxants, selective serotonin reuptake inhibitors (SSRIs), analgesics such as tramadol, and NSAIDs.24 NSAIDs alone have proven several times over to be no more effective at relieving symptoms than placebo. S-adenosyl-methionine (SAMe), an anti-inflamatory agent with analgesic and antidepressant action, has led to improved physical, symptom, and psychological status.24 Benzodiazepines are not advised for long-term use.25
A trial of fluoxetine, titrating the dosage from 20 mg to 80 mg daily, showed that this SSRI significantly alleviated symptoms of pain, fatigue, and depression.26 Several trials of amitriptyline have shown that it reduces pain, sleep difficulties, fatigue, and tender point scores.27-29 Patients start by taking 5 to 10 mg, 1 to 3 hours before bedtime, and increase the dose by 5 mg every 2 weeks based on efficacy and side effects.23 Adding 20 mg of fluoxetine in the morning to 25 mg of amitriptyline at bedtime produces significantly more improvement in global well-being, pain, sleep, and function than is seen with either medication alone.13 This regimen should be used cautiously, because SSRIs can raise blood levels of TCAs. Venlafaxine, 75 mg daily, significantly improved pain and disability, and decreased depression and anxiety, in one study.30 Cyclobenzaprine is effective when started at low doses of 10 to 30 mg before bedtime and titrated up to 40 mg as needed.31 A recent trial found that patients taking a combination tablet of tramadol and acetaminophen (37.5 mg and 325 mg, respectively) reported significantly less pain, better pain relief, and improved physical functioning.32 Duloxetine may also be helpful to some patients.33
In a meta-analysis of 49 studies, treatment with exercise combined with CBT was more efficacious than pharmacologic treatment.34 Thus, nonpharmacologic modalities should be the focus of treatment, with medications offered for symptom control as necessary.
Gradual, low-impact aerobic exercise is recommended at least 3 times a week for 30 minutes at a time to decrease pain, tender points, myalgias, and depression. Exercise also increases physical fitness, strength, and feelings of self-efficacy. CBT teaches specific cognitive and behavioral management skills to patients so they can set goals, prioritize what is important in life, and handle setbacks when they arrive.35
Physical therapy may include stretching, deep tissue massage, heat, transcutaneous electrical nerve stimulation (TENS), myofacial release therapy (muscle stretching and release), ultrasonography, and hydrotherapy.36 Although, according to the literature, these approaches have shown limited effectiveness, many patients may still benefit because these treatments tend to reduce muscle contraction and enhance oxygenation.
Trigger point injections involve 1% lidocaine, with or without saline or a low-dose corticosteroid, injected into tender areas.35 Often used to treat localized pain such as myofascial pain syndrome, these may prove more effective in treating FMS.
Acupuncture showed short-term benefit in patients with FMS who had six sessions of electroacupuncture in correct anatomic points, compared to the control patients, who were exposed to less electrical current and incorrect needle placement.37 Although other studies show pain reduction and increased pain threshold from acupuncture, a few patients withdrew because of exacerbation of symptoms.38,39
Chiropractic manipulation has not been shown to be effective for FMS according to the literature.19 However, it is one of the most commonly used complementary therapies for FMS and warrants further study.40
Electromyographic (EMG) biofeedback has proven useful in significantly reducing pain, morning stiffness, and tender points and is most effective when combined with exercise.41
Hypnotherapy has shown improved outcomes in pain, fatigue upon awakening, sleep disturbance, and global assessment, which may indicate its usefulness as adjunct therapy.42
FMS involves pain and fatigue that does not worsen or become life threatening.43 It is a chronic but stable condition. In several studies, symptoms appear to remain steady, with most patients doing the same or better over time.
The syndrome of fibromyalgia remains a complex entity with no definitive etiology. However, research has progressed in recent years, and the future is likely to bring increased knowledge about the condition, more acceptance of it by patients and providers, and better control of symptoms.
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