Fibromyalgia is a disorder of chronic, widespread musculoskeletal pain associated with fatigue, cognitive dysfunction, mood disorders, and sleep disturbances. Fibromyalgia is a controversial disease entity because there is disagreement about what causes it, how to diagnose it, and how to treat it. Indeed, fibromyalgia cannot be established with an objective laboratory test or imaging.

Many of the presenting symptoms are suggestive of psychological overlay, including ubiquitous pain with a lack of objective signs, allodynia (pain with tactile stimuli that would normally not be painful, such as brushing the skin) and symptoms of depression and anxiety. Regardless, quality of life for patients with fibromyalgia can be severely diminished.

Structure and Function

The underlying pathophysiology of fibromyalgia is unknown. One widely supported mechanism is known as “central sensitization,” whereby central nervous system pain processing becomes dysfunctional and leads to increased sensitivity to pain. Why patients develop this central sensitization with fibromyalgia is thought to be a combination of genetics and environment stimuli.

There is no objective evidence of pathology in the muscles, bones, or soft tissue and there is no evidence of autoimmune or inflammatory processes at work either.

Patient Presentation

The hallmark of fibromyalgia is diffuse pain for more than three months, present at multiple sites, accompanied by fatigue, sleep disturbances, and cognitive complaints. Patients may have episodic pain with exacerbations and times of improvement.

Patients often have somatic complaints such as headache or dizziness, bloating, nausea, and diarrhea. Depressed mood, irritability and anxiety are also frequently reported.

Cognitive symptoms reported by fibromyalgia patients include issues with memory, concentration, and attention, so-called “fibro fog.”

Because fibromyalgia does not cause inflammation, erythema and edema should be absent. Of note, tenderness at a specific number of specific points was, but no longer is, a diagnostic criterion.

Objective Evidence

Fibromyalgia is not diagnosed objectively. Rather, the diagnosis is based on the subjective history of widespread, chronic pain.

Radiographic studies and laboratory testing are recommended not to establish the diagnosis of fibromyalgia (for there are no studies or tests that are able to do that). Rather, tests are used to exclude other diagnoses. The tests that might be used include the following:

  • Antinuclear antibody tests to rule out autoimmune conditions,
  • C-reactive protein levels (or other indirect measures of the acute phase inflammatory response, such as the erythrocyte sedimentation rate) to exclude an inflammatory form of arthritis,
  • Celiac serology to rule out celiac disease,
  • Cyclic citrullinated peptide (ACCP) test, as a positive test for this autoantibody might indicate a diagnosis of rheumatoid arthritis,
  • Thyroid function tests, as low thyroid hormone levels are associated with muscle aches, fatigue, poor concentration and weakness.


It is estimated that fibromyalgia affects approximately 2-4% of the population, with the prevalence in women twice as high as in men. Patients with other painful conditions, such as irritable bowel syndrome, rheumatoid arthritis, and lupus are at greater risk for fibromyalgia.

Differential Diagnosis

When considering a diagnosis of fibromyalgia, the differential diagnosis list can be extensive due to the varied and nonspecific symptoms that might be present. A partial differential diagnosis can include adrenal insufficiency, bursitis, hyperparathyroidism, hypothyroidism, Lyme disease, multiple sclerosis, myasthenia gravis, osteoarthritis, peripheral neuropathies, rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematous, and tendinitis.

Patients with fibromyalgia may have coexisting disease or syndromes such as irritable bowel syndrome, chronic fatigue syndrome, interstitial cystitis, temporomandibular joint disorder, depression, and anxiety.

Red Flags

Signs of inflammation are not characteristic of fibromyalgia and warrant investigation. Complaints of fatigue, sleep disturbances, and cognitive, psychological, or somatic complaints in patients with another known musculoskeletal diagnosis may reflect concurrent fibromyalgia.

Treatment Options and Outcomes

The goals for treatment are reducing symptoms and improving the quality of life for patients. There is no singular treatment that works for all patients. Non-pharmacological interventions such as cognitive behavioral therapy, low-impact cardiovascular exercise, and patient education can be beneficial. Other non-pharmacological options include acupuncture, massage, and stress management.

There are only pharmacological agents approved by the US Food and Drug Administration to treat fibromyalgia: Pregabalin (trade name: Lyrica), an antiepileptic; and Duloxetine (Cymbalta) and Milnacipran (Savella), both serotonin/norepinephrine reuptake inhibitor antidepressants.

Muscle relaxants such as Cyclobenzaprine (Flexeril) and Tizanidine (Zanaflex), anti-seizure medicines such as Gabapentin (Neurontin) and other antidepressants such as Amitriptyline (Elavil) have been used “off-label” by many practitioners.

Analgesics have not been found effective in pain reduction for fibromyalgia patients in multiple studies.

Maintaining a healthy weight, regular exercise, along with treatment of mental health conditions and sleep disturbances might be protective. Exercise and physical activity should be highly encouraged in high-risk individuals.

Management of fibromyalgia can be challenging for patient and provider. There is no cure, there is no one treatment regimen that works for all. Indeed, many pharmacological options that work for one patient might have adverse effects that are poorly tolerated by others.

Risk Factors and Prevention

Risk factors for fibromyalgia include female sex, obesity/overweight, physical inactivity, and poor sleep. Roughly half of the patients diagnosed with fibromyalgia also have a co-morbid psychiatric condition.

Key Terms

Fibromyalgia, Chronic Pain


Recognize the history and symptoms suggestive of fibromyalgia. Identify the likely differentials and limit diagnostics based on presentation. Recognize signs of inflammation and infection that are not associated with fibromyalgia. Maintain an open attitude and establish a therapeutic relationship with the patient.

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