566 Fibromyalgia ALG
provide strongest evidence that reflect both WORKUP
BASIC INFORMATION
DEFINITION
Fibromyalgia (FM) is a syndrome characterized
by chronic, widespread musculoskeletal pain
without evidence of soft tissue inflammation.
Key features include fatigue, sleep disrup-
tion, cognitive disturbance, and psychiatric and
somatic symptoms. Research suggests that FM
is a disorder of pain regulation, which is often
classified as a form of central sensitization.
SYNONYMS
“Fibrositis” is a term that is no longer used,
because there is no evidence of connective
tissue inflammation in FM.
FM
ICD-10CM CODE
M79.7 Fibromyalgia
EPIDEMIOLOGY &
DEMOGRAPHICS
Worldwide, the prevalence of FM is estimated
to be between 2% and 8%, and it increases
with age. In the U.S., FM is the most common
cause of musculoskeletal pain in women aged
20 to 55 yr. Using the 2010 American College of
Rheumatology (ACR) diagnostic criteria for FM,
the female:male ratio is approximately 2:1.
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) musculoskel-
etal pain
• Cognitive disturbances
• Fatigue and sleep disturbances (e.g., unre-
freshed sleep, easy fatigability)
• Psychiatric symptoms (e.g., anxiety,
depression)
• Headache (present in more than half of
patients with FM; this includes migraine and
tension-type headaches)
• Paresthesias
• Associated disorders: Irritable bowel syn-
drome, interstitial cystitis/painful bladder
syndrome
On physical examination, patients with FM may
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 pres-
sure (4 kg/cm2 or enough pressure to whiten the
nail bed of the fingertips of the examiner).
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 both the ascend-
ing and descending pain pathways operate
abnormally, resulting in central amplification
of pain signals. Familial associations of FM
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these factors.
• In those predisposed, FM may be precipi-
tated by stressful events such as abuse,
injury from accidents, illnesses (including
autoimmune disorders), infections, surgical
procedures, and psychological stressors.
• Psychosocial, neuroendocrine, hormonal, and
sociocultural factors also influence symptom
expression.
PATHOGENESIS
Much remains to be discovered about the
pathogenesis of FM, even though significant
advances have been made in our understand-
ing of this syndrome 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).
• Afflicted persons show altered physiologic
responses to painful stimulation at spinal and
supraspinal levels.
• Brain neuroimaging studies found differ-
ences in brain structure, neurochemical con-
centrations, 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.
• Pain augmentation may also result from a
loss of tonic inhibition by descending inhibi-
tory pathways from the brain to the spinal
cord.
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
The presence of any of the disorders mentioned
below does not necessarily exclude a diagnosis
of FM because it may coexist with many condi-
tions:
• Other functional somatic or “central sensi-
tivity” syndromes: Myofascial pain, chronic
fatigue syndrome, irritable bowel syndrome,
headache/migraines, chronic pelvic and
bladder pain disorders, and temporoman-
dibular disorder
• Disorders that can mimic FM and must be
ruled out include metabolic (e.g., hypothy-
roidism), infectious, and neurologic disorders.
Arthritis and rheumatic diseases (e.g., rheu-
matoid arthritis, systemic lupus erythemato-
sus, 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
A thorough history, physical examination, and
appropriately selected laboratory or imaging
studies can usually differentiate FM from con-
nective tissue or other systemic diseases.
• Chronic (>3 mo) widespread pain is the
hallmark symptom of FM, but fatigue, ten-
derness, depression/anxiety, nonrestorative
sleep, cognitive difficulties (the so-called
“fibrofog”), and functional impairment are
other key symptoms.
• The 1990 ACR FM Classification Criteria were
used for clinical studies:
1. Chronic, widespread pain in all four quad-
rants 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
the musculoskeletal pain must be excluded
(Table 1).
• A diagnostic screening tool (Fibromyalgia
Diagnostic Screen) developed by Arnold and
colleagues 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. 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 6 of 9 possible pain sites, and moder-
ate to severe sleep disturbance or fatigue.
LABORATORY TESTS
• Selective use of ancillary tests complements
the history and physical examination in the
diagnosis of FM. Testing should be highly
focused on the exclusion of FM mimickers or
suspected concurrent diseases.
• Complete blood cell count, routine chem-
istries, 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 stud-
ies (low levels can cause fatigue and depres-
sive 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 sug-
gest 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, anxi-
ety, poor sleep).
• Challenging to treat; best approach may be
combination of drug and nondrug therapies.
 ALG Fibromyalgia 567

• Avoid narcotic use. Opioid use and abuse

TABLE 1  2010 Fibromyalgia Diagnostic Criteria

Criteria
may aggravate chronic widespread pain.
F
DISPOSITION
A patient satisfies diagnostic criteria for fibromyalgia if the following three conditions are met:
1. Widespread pain index (WPI) 7 and symptom severity (SS) scale score of 5 or WPI 3-6 and SS scale score of 9. • The pain and symptoms of FM can wax and
2. Symptoms have been present at a similar level for at least 3 mo. wane, vary in physical location and in inten-
3. The patient does not have a disorder that would otherwise explain the pain. sity day-to-day; many patients continue to
Ascertainment have chronic pain and fatigue regardless of
1. WPI: Note the number of areas in which the patient has had pain over the past wk. In how many areas therapy.
has the patient had pain? • Disability rates vary from 10% to 30%.
Score will be between 0 and 19.
Shoulder girdle, left Hip (buttock, trochanter), left Jaw, left Upper back
REFERRAL

and Disorders
Diseases
Shoulder girdle, right Hip (buttock, trochanter), right Jaw, right Lower back Referral to rheumatology, neurology, mental
Upper arm, left Upper leg, left Chest Neck health professionals, physical medicine and
Upper arm, right Upper leg, right Abdomen rehabilitation, including PT. Multidisciplinary
Lower arm, left Lower leg, left team approach is generally most helpful.
Lower arm, right Lower leg, right
2. SS scale score:
PEARLS &
Fatigue
Waking unrefreshed CONSIDERATIONS I
Cognitive symptoms
For the each of the three symptoms above, indicate the level of severity over the past week using the following scale: • Fibromyalgia is a neurosensory disorder
0, No problem whereby affected individuals have abnormal
1, Slight or mild problems, generally mild or intermittent
central nociceptive processing.
2, Moderate, considerable problems, often present at a moderate level
3, Severe: Pervasive, continuous, life-disturbing problems • Diagnosis is based on the presence of chron-
Considering somatic symptoms in general, indicate whether the patient has:* ic musculoskeletal pain in the absence of
0, No symptoms physical or laboratory evidence of inflamma-
1, Few symptoms tion and in the absence of any other condition
2, A moderate number of symptoms that would explain the symptoms.
3, A great deal of symptoms • Treatment options are varied, but a combina-
The SS scale score is the sum of the severity of the three symptoms (fatigue, waking unrefreshed, cognitive tion of drug and nondrug options is likely to
symptoms) plus the extent (severity) of somatic symptoms in general. The final score is between 0 and 12. provide optimal results.
*Somatic symptoms that might be considered include muscle pain, irritable bowel syndrome, fatigue or tiredness, thinking or re- • Myofascial pain syndrome may represent a
membering problem, muscle weakness, headache, pain or cramps in the abdomen, numbness or tingling, dizziness, insom- localized form of FM. It is associated with
nia, depression, constipation, pain in the upper abdomen, nausea, nervousness, chest pain, blurred vision, fever, diarrhea, dry trigger points (rather than tender points as
mouth, itching, wheezing, Raynaud phenomenon, hives or welts, ringing in ears, vomiting, heartburn, oral ulcers, loss of or seen in FM). Some patients with myofascial
change in taste, seizures, dry eyes, shortness of breath, loss of appetite, rash, sun sensitivity, hearing difficulties, easy bruis-
ing, hair loss, frequent urination, painful urination, and bladder spasms. pain syndrome may progress to FM.
Adapted from Wolfe F et al: The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measure-
ment of symptom severity, Arthritis Care Res 62:600-610, 2010. COMMENTS
FM occurs frequently in patients with some
• Nonpharmacologic (Table 2): Strong evidence • Best evidence for tricyclics (low-dose ami- rheumatic diseases, such as rheumatoid arthri-
to support exercise (aerobic, strengthen- triptyline, cyclobenzaprine), serotonin-nor- tis, ankylosing spondylitis, and systemic lupus
ing, and stretching exercises; tai chi; yoga), epinephrine reuptake inhibitors (milnacipran, erythematosus, in which prevalence of FM may
cognitive behavioral therapy, physical ther- duloxetine), gabapentinoids (gabapentin, reach 20%.
apy, and patient education (e.g., regarding pregabalin).
the disease, importance of good sleep and • Second-tier drug classes include SSRIs. SUGGESTED READINGS
hygiene). • “Start low, go slow” approach is best to avoid Available at ExpertConsult.com
• FM can be due to abnormalities in many side effects, which are common. Medication
different neurotransmitter systems; thus, adherence is generally poor. RELATED CONTENT
approaches and treatment responses may • There is no evidence that acetaminophen,
Fibromyalgia (Patient Information)
vary. NSAIDs or corticosteroids are effective in FM.
• Pharmacologic therapies for fibromyalgia are • The only analgesic that has demonstrated AUTHOR: Nadine Mbuyi, MD
summarized in Table 3. some efficacy in FM has been tramadol; can
consider for treatment-resistant cases.

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568 Fibromyalgia ALG

TABLE 2  Nonpharmacologic Therapies for Fibromyalgia

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

CNS, Central nervous system; FM, fibromyalgia.

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

TABLE 3  Pharmacologic Therapies for Fibromyalgia

Treatment
Pharmacologic thera-
pies
Tricyclic compounds
Serotonin norepi-
nephrine reuptake
inhibitors
Cost Specifics Evidence level Side Effects Suggestions
Pharmacologic therapy 5, Consensus ● Some practitioners
is best chosen find that getting
based on the patients on a drug
predominant symp- regimen that helps
toms and initiated improve symptoms
in low dose with before initiating non-
slow dose escala- pharmacologic thera-
tion. pies can help improve
compliance.
● Amitriptyline 10- 1, A Dry mouth, weight ● When effective, can
70 mg qhs gain, constipa- improve a wide
● Cyclobenzaprine tion, “groggy” or range of symptoms,
5-20 mg qhs drugged feeling including pain, sleep,
bowel, and bladder
symptoms.
● Taking these drugs
several hours before
bedtime improves
side effect profile.
Duloxetine is generic, ● Duloxetine, 30- 1, A Nausea, palpitations, ● Warning patients
milnacipran not 120 mg/day headache, fatigue, about transient
● Milnacipran, 100- tachycardia, hyper- nausea, taking with
200 mg/day tension food, and slowly
increasing dose can
increase tolerability.
● Milnacipran might
be slightly more
­noradrenergic than
­duloxetine and thus
­potentially more help-
ful for fatigue and
memory problems,
but it is also more
likely to cause HTN.

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 ALG Fibromyalgia 569

TABLE 3  Pharmacologic Therapies for Fibromyalgia—cont’d

Treatment Cost Specifics Evidence level Side Effects Suggestions
F
Gabapentinoids Gabapentin is generic, ● Gabapentin 800- 1, A Sedation, weight gain, ● Giving most or all of
pregabalin not 2400 mg/day in di- dizziness the dose at bedtime
vided doses can increase tolera-
● Pregabalin up to bility.
600 mg/day in di-
vided doses
γ-Hydroxybutyrate Available for treating GHB 4.5-6.0 g per 1, A Sedation, respiratory ● Shown to be effica-
narcolepsy, cata- night in divided depression, and cious but not
plexy doses death approved by U.S.
FDA because of

and Disorders
Diseases
safety concerns.
Low-dose naltrexone Low 4.5 mg/day Two small single
center RCTs
Cannabinoids NA Nabilone 0.5 mg PO 1, A Sedation, dizziness, ● No synthetic canna-
qhs-1.0 mg bid dry mouth binoid is approved in
the U.S. for treat-
ment of pain. I
Selective serotonin SSRIs that should be Fluoxetine, sertraline, 1, A Nausea, sexual dys- ● Older, less selective
reuptake inhibitors used in FM (see paroxetine function, weight SSRIs may have
(SSRIs) Suggestions) are all gain, sleep distur- some efficacy in
generic bance improving pain,
­especially at higher
doses that have
more prominent nor-
adrenergic effects.
● Newer SSRIs (citalo-
pram, escitalopram,
desvenlafaxine) are
less effective or
­ineffective as
­analgesics.
NSAIDs ● No evidence of ef- 5, D GI, renal, and cardiac ● Use the lowest dose
ficacy side effects for the shortest
● Can be helpful to period of time to
treat comorbid reduce side effects.
“peripheral pain
generators”
Opioids ● Tramadol with or 5, D Sedation, addiction, ● There is increasing
without acetamino- tolerance, opioid- evidence that opioids
phen, 50-100 mg induced hyperalgesia are less effective for
every 6 hours treating chronic pain
● No evidence of effi- than previously
cacy for stronger thought, and their
opioids 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.

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2020. For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
 Fibromyalgia 569.e1

SUGGESTED READINGS
Albrecht DS et al: Brain glial activation in fibromyalgia–a multi-site positron emis-
sion tomography investigation, Brain Behav Immun 75:72, 2019.
Arnold LM et al: Development and testing of the fibromyalgia diagnostic screen
for primary care, J Womens Health 21:231-239, 2012.
Arnold LM et al: AAPT diagnostic criteria for fibromyalgia, J Pain 20(6):611-628,
2019.
Choy E et al: A systematic review and mixed treatment comparison of the effi-
cacy of pharmacological treatments for fibromyalgia, Semin Arthritis Rheum
41:335-345, 2011.
Clauw DJ: Fibromyalgia a clinical review, JAMA 311:1547-1555, 2014.
Clauw DJ et al: The science of fibromyalgia, Mayo Clin Proc 86:907-911, 2011.
Derry S et al: Pregabalin for pain in fibromyalgia in adults, Cochrane Database
Syst Rev 9:CD011790, 2016.
Fitzcharles MA et al: Opioid use, misuse, and abuse in patients labeled as fibro-
myalgia, Am J Med 124:955-960, 2011.
Foerster B et al: Cerebral blood flow alterations in pain-processing regions of
patients with fibromyalgia using perfusion MR imaging, Am J Neuroradiol
32:1873-1878, 2011.
Goldenberg D et al: Opioid use in fibromyalgia: a cautionary tale, Mayo Clin Proc
91:640-648, 2016.
Hawkins RA: Fibromyalgia: a clinical update, J Am Osteopath Assoc 113:680-689,
2013.
Kodner C: Common questions about the diagnosis and management of fibromy-
algia, Am Fam Physician 91:472-478, 2015.
Macfarlane G et al: EULAR revised recommendations for the management of
fibromyalgia, Ann Rheum Dis 76(2):318-328, 2017.
Neira SR et al: Effectiveness of aquatic therapy vs land-based therapy for bal-
ance and pain in women with fibromyalgia: a study protocol for a randomised
controlled trial, BMC Musculoskelet Disord 18(22), 2017.
Tomas-Carus P et al: Breathing exercises must be a real and effective intervention
to consider in women with fibromyalgia: a pilot randomized controlled trial,
J Altern Complem Med, 2018.
Wang C et al: Effect of tai chi versus aerobic exercise for fibromyalgia: compara-
tive effectiveness randomized controlled trial, BMJ 360:k851, 2018.
Wolfe F et al: The American College of Rheumatology preliminary diagnostic
criteria for fibromyalgia and measurement of symptom severity, Arthritis Care
Res 62:600, 2010.

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2020. For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.