Fibromyalgia

AUTHORS: Helen Zhang, BS, and Manuel F. DaSilva, MD

Definition

Fibromyalgia (FM) is a syndrome characterized by chronic, widespread musculoskeletal pain without evidence of soft tissue inflammation. Key features include chronic fatigue, sleep disruption, cognitive disturbance, and psychiatric and somatic symptoms. FM can be considered a centralized pain state, with research suggesting that it is a disorder of pain regulation.

Synonyms

The term “fibrositis” is no longer used because there is no evidence of connective tissue inflammation in FM.

ICD-10CM CODE
M79.7		Fibromyalgia

Epidemiology & Demographics

Worldwide, the prevalence of FM is estimated to be between 2% and 8%, increasing with age. FM is most commonly diagnosed in women between ages 40 and 60 yr, but can affect all ages and populations.¹

Physical Findings & Clinical Presentation

Patients with FM often report the following symptoms:

Chronic (>3 mo) widespread (affecting both sides of the body, above and below the waist, and involving the axial spine) musculoskeletal pain with tenderness to palpation of at least 11 of the 18 specific tender points associated with FM ²
Cognitive disturbances
Fatigue and sleep disturbances
Psychiatric symptoms (e.g., anxiety, depression)
Headache (present in more than half of patients with FM; includes migraine and tension-type headaches)
Paresthesias
Associated disorders: Irritable bowel syndrome, interstitial cystitis/painful bladder syndrome

On physical examination, patients with FM can have tenderness, in particular soft tissue locations called tender points. Examination of tender points requires that the examiner be familiar with the areas to palpate and that they apply enough pressure (4 kg/cm² or enough to whiten the nail bed of the examiner’s fingertips).

Etiology

Although the exact cause of FM is unknown, its etiology is thought to be multifactorial:

Genetic and environmental factors may play a role. Evidence suggests that ascending and descending pain pathways operate abnormally, resulting in central amplification of pain signals.³ Familial associations of FM provide the strongest evidence that reflects both these factors.
In those predisposed, FM may be precipitated by physical or psychologic stress such as abuse, injury from accidents, illnesses (including autoimmune disorders), infections, and surgical procedures.
Psychosocial, neuroendocrine, hormonal, and sociocultural factors also influence symptom expression.⁴

Pathogenesis

Much remains to be discovered about the pathogenesis of FM, although significant advances have been made over the past few decades. Researchers have shown that biochemical, metabolic, and immunoregulatory abnormalities exist in patients with FM. Hence, this condition is now believed to be neurosensory in nature.

Augmented pain and sensory processing is a hallmark, resulting in diffuse pain, allodynia (pain brought on by nonpainful stimuli), and hyperalgesia (more intense and prolonged pain perception).⁵
Brain imaging studies have demonstrated evidence of increased activation in pain processing networks, suggesting abnormal hyperactivity of pain detection and processing pathways.
Afflicted persons show altered physiologic responses to painful stimulation at spinal and supraspinal levels.
Brain neuroimaging studies have identified differences in brain structure, neurochemical concentrations, and functional brain networks in FM compared with control subjects. PET scans have revealed widespread activation of glial cells in the cortex, particularly in the frontal and parietal lobes.⁶
Pain augmentation may also result from a loss of tonic inhibition by descending inhibitory pathways from the brain to the spinal cord.⁷

Diagnosis ⬆ ⬇

Differential Diagnosis

The presence of any of the disorders below does not necessarily exclude a diagnosis of FM because it can coexist with many conditions:

Other functional somatic or “central sensitivity” syndromes: Myofascial pain, chronic fatigue syndrome, irritable bowel syndrome, headache/migraines, chronic pelvic and bladder pain disorders, and temporomandibular disorder
Disorders that can mimic FM and must be ruled out include metabolic (e.g., hypothyroidism), infectious, and neurologic disorders
Arthritis and rheumatic diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, Sjögren syndrome)
Myalgias and other muscle disease (e.g., inflammatory and metabolic myopathies)
Mood and anxiety disorders
Sleep disorders (e.g., sleep apnea, restless leg syndrome)
Neurologic disorders
Medications: Statin-induced muscle pain, opioid-induced hyperalgesia ⁸

Workup

A thorough history, physical examination, and appropriately selected laboratory or imaging studies can usually differentiate FM from connective tissue or other systemic diseases.

Chronic (>3 mo) widespread pain is the hallmark symptom of FM, but fatigue, tenderness, depression/anxiety, nonrestorative sleep, cognitive difficulties (“fibrofog”), and functional impairment are other key symptoms.
The 1990 ACR FM Classification Criteria used for clinical studies:
1. Chronic, widespread pain in all four quadrants of the body and the axial skeleton
2. Pain on digital palpation of at least 11 of 18 tender points
The 2010 ACR diagnostic criteria for FM do not require a tender point examination; other disorders that would otherwise explain musculoskeletal pain must be excluded (Table 1).
A diagnostic screening tool (Fibromyalgia Diagnostic Screen) developed by Arnold et al ⁹ was found to accurately screen for FM. This tool includes a patient self-reported questionnaire and an abbreviated physical examination with targeted lab tests.
The most recent FM diagnostic criteria are by ACTION-APS Pain Taxonomy (AAPT), an international working group.¹⁰ To fulfill AAPT criteria for FM, a patient is required to have a history of at least 3 mo of widespread pain in at least six of nine possible pain sites, and moderate to severe sleep disturbance or fatigue.

TABLE 1 2010 Fibromyalgia Diagnostic Criteria

Criteria
A patient satisfies diagnostic criteria for fibromyalgia if the following three conditions are met: Widespread pain index (WPI) 7 and symptom severity (SS) scale score of 5 or WPI 3-6 and SS scale score of 9. Symptoms have been present at a similar level for at least 3 mo. The patient does not have a disorder that would otherwise explain the pain.
Ascertainment
WPI: Note the number of areas in which the patient has had pain over the past week. In how many areas has the patient had pain? Score will be between 0 and 19.
Shoulder girdle, left Shoulder girdle, right Upper arm, left Upper arm, right Lower arm, left Lower arm, right	Hip (buttock, trochanter), left Hip (buttock, trochanter), right Upper leg, left Upper leg, right Lower leg, left Lower leg, right	Jaw, left Jaw, right Chest Abdomen	Upper back Lower back Neck
2. SS scale score: Fatigue Waking unrefreshed Cognitive symptoms For each of the three symptoms above, indicate the level of severity over the past week using the following scale: 0, No problem 1, Slight or mild problems, generally mild or intermittent 2, Moderate, considerable problems, often present at a moderate level 3, Severe: Pervasive, continuous, life-disturbing problems Considering somatic symptoms in general, indicate whether the patient has:∗ 0, No symptoms 1, Few symptoms 2, A moderate number of symptoms 3, A great deal of symptoms The SS scale score is the sum of the severity of the three symptoms (fatigue, waking unrefreshed, cognitive symptoms) plus the extent (severity) of somatic symptoms in general. The final score is between 0 and 12.

^∗Somatic symptoms that might be considered include muscle pain, irritable bowel syndrome, fatigue or tiredness, thinking or memory problems, muscle weakness, headache, pain or cramps in the abdomen, numbness or tingling, dizziness, insomnia, depression, constipation, pain in the upper abdomen, nausea, nervousness, chest pain, blurred vision, fever, diarrhea, dry mouth, itching, wheezing, Raynaud phenomenon, hives or welts, ringing in ears, vomiting, heartburn, oral ulcers, loss of or change in taste, seizures, dry eyes, shortness of breath, loss of appetite, rash, sun sensitivity, hearing difficulties, easy bruising, hair loss, frequent urination, painful urination, and bladder spasms.

Adapted from Wolfe F et al: The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity, Arthritis Care Res 62:600-610, 2010.

Laboratory Tests

Selective use of ancillary tests complements the history and physical examination in diagnosis of FM. Testing should be highly focused on the exclusion of FM mimickers or suspected concurrent diseases.
Complete blood cell count, routine chemistries, thyroid-stimulating hormone (TSH), 25-hydroxy vitamin D level (low levels can cause muscle pain), vitamin B₁₂ level (low levels can cause fatigue and pain), iron studies (low levels can cause fatigue and depressive symptoms), and magnesium levels (low levels can cause muscle spasms).
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are generally normal.
Routine testing for antinuclear antibody (ANA) and/or rheumatoid factor should be avoided unless history and physical examination suggest an autoimmune disease.

Treatment ⬆ ⬇

General Rx

The goal in treating patients with fibromyalgia is to reduce the main symptoms of the syndrome (musculoskeletal pain, fatigue, depression, anxiety, poor sleep). The revised Fibromyalgia Impact Questionnaire (FIQR) (Fig. E1) is useful to assess functional status as well as overall impact and fibromyalgia symptoms.

Challenging to treat; best approach may be combination of drug and nondrug therapies.
Nonpharmacologic (Table E2): There is evidence to support exercise (aerobic, strengthening, and stretching exercises), cognitive behavioral therapy, physical therapy, and patient education (e.g., regarding the disease, importance of good sleep and hygiene). However there is little high-quality, adequately powered evidence to support the various therapy classes.¹¹
FM can be due to abnormalities in many different neurotransmitter systems; thus, approaches and treatment responses may vary.
Pharmacologic therapies for fibromyalgia are summarized in Table 3.
Best evidence for tricyclics (low-dose amitriptyline, cyclobenzaprine), serotonin-norepinephrine reuptake inhibitors (milnacipran, duloxetine), gabapentinoids (gabapentin, pregabalin).
Second-tier drug classes include SSRIs.
“Start low, go slow” approach is best to avoid side effects, which are common.
Medication adherence is generally poor.
There is no evidence that acetaminophen, NSAIDs, or corticosteroids are effective in FM.
The only analgesic that has demonstrated some efficacy in FM has been tramadol; can consider for treatment-resistant cases.
Avoid narcotic use. Opioid use and abuse may aggravate chronic widespread pain.
The pain and symptoms of FM can wax and wane, vary in physical location and in intensity day-to-day; many patients continue to have chronic pain and fatigue regardless of therapy.
Disability rates vary from 10% to 30%.

TABLE 3 Pharmacologic Therapies for Fibromyalgia

Treatment	Cost	Specifics	Evidence level	Side Effects	Suggestions
Pharmacologic therapies		Pharmacologic therapy is best chosen based on the predominant symptoms and initiated in low dose with slow dose escalation.	5, Consensus		Some practitioners find that getting patients on a drug regimen that helps improve symptoms before initiating nonpharmacologic therapies can help improve compliance.
Tricyclic compounds		Amitriptyline 10-70 mg qhs Cyclobenzaprine 5-20 mg qhs	1, A	Dry mouth, weight gain, constipation, “groggy” or drugged feeling	When effective, can improve a wide range of symptoms, including pain, sleep, bowel, and bladder symptoms. Taking these drugs several hours before bedtime improves side effect profile.
Serotonin norepinephrine reuptake inhibitors	Duloxetine is generic, milnacipran not	Duloxetine, 30-120 mg/day Milnacipran, 100-200 mg/day	1, A	Nausea, palpitations, headache, fatigue, tachycardia, hypertension	Warning patients about transient nausea, taking with food, and slowly increasing dose can increase tolerability. Milnacipran might be slightly more noradrenergic than duloxetine and thus potentially more helpful for fatigue and memory problems, but it is also more likely to cause HTN.
Gabapentinoids	Gabapentin is generic, pregabalin not	Gabapentin 800-2400 mg/day in divided doses Pregabalin up to 600 mg/day in divided doses	1, A	Sedation, weight gain, dizziness	Giving most or all of the dose at bedtime can increase tolerability.
γ-Hydroxybutyrate	Available for treating narcolepsy, cataplexy	GHB 4.5-6.0 g per night in divided doses	1, A	Sedation, respiratory depression, and death	Shown to be efficacious but not approved by U.S. FDA because of safety concerns.
Low-dose naltrexone	Low	4.5 mg/day	Two small single center RCTs
Cannabinoids	NA	Nabilone 0.5 mg PO qhs-1.0 mg bid	1, A	Sedation, dizziness, dry mouth	No synthetic cannabinoid is approved in the U.S. for treatment of pain.
Selective serotonin reuptake inhibitors (SSRIs)	SSRIs that should be used in FM (see Suggestions) are all generic	Fluoxetine, sertraline, paroxetine	1, A	Nausea, sexual dysfunction, weight gain, sleep disturbance	Older, less selective SSRIs may have some efficacy in improving pain, especially at higher doses that have more prominent noradrenergic effects. Newer SSRIs (citalopram, escitalopram, desvenlafaxine) are less effective or ineffective as analgesics.
NSAIDs		No evidence of efficacy Can be helpful to treat comorbid “peripheral pain generators”	5, D	GI, renal, and cardiac side effects	Use the lowest dose for the shortest period of time to reduce side effects.
Opioids		Tramadol with or without acetaminophen, 50-100 mg every 6 hr No evidence of efficacy for stronger opioids	5, D	Sedation, addiction, tolerance, opioid-induced hyperalgesia	There is increasing evidence that opioids are less effective for treating chronic pain than previously thought, and their risk-benefit profile is worse than other classes of analgesics.

bid, Twice a day; FDA, U.S. Food and Drug Administration; FM, fibromyalgia; GHB, gammahydroxybutyrate; GI, gastrointestinal; HTN, hypertension; NSAIDs, nonsteroidal antiinflammatory drugs; PO, oral; qhs, at bedtime; RCT, randomized controlled trial.

From Hochberg MC: Rheumatology, ed 7, Philadelphia, 2019, Elsevier.

Figure E1 The Revised Fibromyalgia Impact Questionnaire (Fiqr) Assesses Functional Status as Well as the Overall Impact and Fibromyalgia (Fm) Symptoms

The Fiqr Total Score Can Be Used as an Outcome Measure in Clinical Studies. The Fiqr Function Score and the Symptom Scores Can Be Used Individually to Determine Severity. Paper and Online Versions Perform Similarly, and the Fiqr Performs Similarly to its Original Version.

From Firestein GS et al: Firestein & Kelley’s textbook of rheumatology, ed 11, Philadelphia, 2021, Elsevier.

TABLE E2 Nonpharmacologic Therapies for Fibromyalgia

Treatment	Cost	Specifics	Evidence Level	Side Effects	Suggestions
Patient education	Low	Incorporate principles of self-management, including a multimodal approach.	1, A		After initial diagnosis, spend several visits (or use separate educational sessions) to explain the condition and set treatment expectations.
Graded exercise	Low	Aerobic exercise has been best studied, but strengthening and stretching also have been shown to be of value.	1, A	Worsening of symptoms when program is begun too rapidly	Counsel patients to “start low, go slow.” For many patients, focusing first on increasing daily “activity” is more helpful before actually starting exercise.
Cognitive behavioral therapy (CBT)	Low	Pain-based CBT programs have been shown to be effective in one-on-one settings, small groups, and via the Internet.	1, A	No significant side effects of CBT per se, but patients’ acceptance is often poor when they view this as a “psychologic” intervention	Internet-based programs are gaining acceptance and are more convenient for working patients.
Complementary and alternative medicine (CAM) therapies	Variable	Most CAM therapies have not been rigorously studied.	1, A	Generally safe	There is emerging evidence that CAM treatments such as tai chi, yoga, balneotherapy, and acupuncture might be effective. Allowing patients to choose which CAM therapies to incorporate into an active treatment program can increase self-efficacy.
CNS neurostimulatory therapies		Several different types of CNS neurostimulatory therapies have been shown to be effective in FM and other chronic pain states.		Headache	These treatments continue to be refined as we learn about optimal stimulation targets, “dosing,” and so on.

CNS, Central nervous system; FM, fibromyalgia.

From Hochberg MC: Rheumatology, ed 7, Philadelphia, 2019, Elsevier.

Referral

Referral to rheumatology, neurology, mental health professionals, physical medicine and rehabilitation, including PT. Multidisciplinary team approach is generally most helpful.

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Basic Information ⬇

Diagnosis ⬆ ⬇

Treatment ⬆ ⬇

Pearls & Considerations ⬆ ⬇

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