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Fibromyalgia
F. Stuart Leeds, MD, MS
image BASICS
DESCRIPTION
  • Chronic, widespread noninflammatory musculoskeletal pain syndrome with multisystem manifestations. Although the specific pathophysiology has not been elucidated, it is generally thought to be a disorder of altered central pain regulation.
  • Synonym(s): FMS; fibrositis, fibromyositis (misnomers); “psychogenic rheumatism” (archaic and inaccurate)
EPIDEMIOLOGY
Incidence
  • Predominant sex: female > male (70-90% are females) (1)
  • Predominant age range: 20 to 65 years
Prevalence
2-5% of adult U.S. population (2); 8% of primary care patients
ETIOLOGY AND PATHOPHYSIOLOGY
  • Idiopathic, but appears to be a primary disorder of central pain processing, termed central sensitization (3). Afferent augmentation of peripheral nociceptive stimuli
  • Alterations in neuroendocrine, neuromodulation, neurotransmitter, neurotransporter, biochemical, and neuroreceptor function/physiology
  • Sleep abnormalities—&agr;-wave intrusion (4)
  • Inflammation is not a feature of fibromyalgia.
Genetics
  • Genetics
    • High familial aggregation
    • Inheritance is unknown but likely polygenic.
    • Odds ratio may be as high as 8.5 for a first-degree relative of a familial proband (5).
  • Environmental—several triggers have been described:
    • Physical trauma or severe illness
    • Stressors (e.g., work, family, life events, and physical/sexual abuse)
    • Viral and bacterial infections
RISK FACTORS
  • Female gender
  • Poor functional status
  • Negative/stressful life events
  • Low socioeconomic status
GENERAL PREVENTION
No known strategies for prevention.
COMMONLY ASSOCIATED CONDITIONS
  • Often a comorbid condition with other rheumatologic or neurologic disorders
  • Obesity is frequently present and is associated with increased severity of symptoms (6).
image DIAGNOSIS
  • Original 1990 ACR criteria, still widely used: (i) pain in all four quadrants, (ii) axial (neck/spine) involvement, (iii) tender points (TPs) ≥11, (iv) no other explanation for symptoms (2)
  • Per the 2010 revised ACR criteria (2)
    • Based on Widespread Pain Index (WPI) and Symptom Score (SS)
      • Must have (WPI ≥7 + SS ≥5) or (WPI ≥3 and SS ≥9); and
      • Symptoms for >3 months; and
      • No other explanation for these symptoms
  • A questionnaire tool to facilitate WPI/SS patient scoring and diagnosis may be found at: www.fmnetnews.com/docs/NewFibroCriteriaSurvey.pdf
  • This tool assesses the following:
    • WPI counts the number of sites of regional pain occurring over past week (score 0 to 19 sites)
    • The SS scale score is the sum of two parts.
      • Part 1 grades the three key symptoms: fatigue, waking unrefreshed, and cognitive symptoms
      • Part 2 counts 40 + associated symptoms, ranking them from “none” to “many”
      • The parts are added together to give a total SS of 0 to 12.
  • The Visual Analogue Scale Fibromyalgia Impact Questionnaire (VASFIQ) (7) is recommended for initial and serial assessment of patient's functional status. It may be found at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383533/figure/fig1-1759720X11416863/
  • Enhancements to the 2010 criteria, termed 2011modCr and 2013altCr (8) have been proposed, but are not yet widely accepted.
PHYSICAL EXAM
  • Classic fibromyalgia TPs: 9 symmetric pairs (5 anterior, 4 posterior) located at anterior sternocleidomastoids, upper mid-trapezius, medial 2nd intercostal spaces, lateral epicondyles, medial fat pad of knees, and posteriorly, at occipital insertions, upper medial scapular insertions, upper outer quadrants of gluteals, and posterior greater trochanters. The presence of ≥11 TPs carries a sensitivity of 88.4% and specificity 81.1% for the disease (2). These are distinct from the “trigger points” found in myofascial pain syndrome.
  • Joints examined for swelling, tenderness, erythema, decreased range of motion, crepitus, and cystic or mass lesions—all typically absent in isolated fibromyalgia.
  • Document absence of inflammatory musculoskeletal disease features (e.g., no synovitis, enthesopathy, dermatologic/ocular findings)
  • Neurologic exam: may demonstrate generalized or “nonanatomic” dysethesia, hyper- or hypesthesia
DIFFERENTIAL DIAGNOSIS
  • RA, SLE, sarcoidosis, and other inflammatory connective tissue disorders
  • Diffuse/advanced OA
  • Seronegative spondyloarthropathies (AS, psoriatic arthritis, etc.)
  • Polymyalgia rheumatica
  • Inherited myopathies
  • Drug-induced and endocrine myopathies
  • Viral/postviral polyarthralgia
  • Anemia and iron deficiency
  • Electrolyte disturbances: Mg, Na, K, Ca
  • Obstructive sleep apnea
  • Osteomalacia/vitamin D deficiency
  • Opioid-induced hyperalgesia
  • Hypothyroidism
  • Multiple sclerosis
  • Lyme disease
  • Hepatitis B and C (chronic)
  • Inclusion-body myositis
  • Spinal stenosis/neuropathies
  • Peripheral vascular disease
  • Somatoform disorder
  • Overlap syndromes
    • Chronic fatigue syndrome/chronic fatigue immune dysfunction syndrome (CFIDS)
    • Myofascial pain syndrome (more anatomically localized than fibromyalgia, but they may co-occur)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • CBC with differential, ESR or CRP, CPK, TSH, comprehensive metabolic profile; consider 25-OH vitamin D, Mg, B12, folate, and urine drug screen
  • ANA, RF, and other rheumatologic labs unnecessary, unless there is evidence of an inflammatory connective tissue disorder.
  • Imaging is not indicated, except to exclude other diagnoses.
Diagnostic Procedures/Other
  • Sleep studies may be indicated to rule out obstructive sleep apnea or narcolepsy.
  • Consider psychiatric or neuropsychiatric evaluation for mood disorders and cognitive disturbances.
image TREATMENT
According to the HHS National Guideline Summary (10) and other sources, evidence-based interventions include the following:
  • Nonpharmacologic treatment critical to successful outcomes
  • Nonpharmacologic
    • Educate the patient about the diagnosis, signs, symptoms, and treatment options (10)[A].
    • Provide Internet education resources.
      • www.fmaware.org
      • www.nfra.net
      • www.fmnetnews.com
    • Use the VASFIQ for initial assessment and interval evaluation during treatment (10)[A].
    • Cognitive-behavioral therapy improves mood, energy, pain, and functional status (10)[A].
    • Aerobic exercise: moderately intense, with gradual progression to avoid symptom exacerbation (11)[A]
    • Weight loss may augment the benefits of exercise.
    • Strength/resistance training—mild to moderate (11)[A]
    • Aquatic exercise training (12)[A]
    • Sleep hygiene
  • P.381

  • Pharmacologic
    • The three FDA-approved drugs are duloxetine, milnacipran, and pregabalin; others are used off-label.
MEDICATION
First Line
  • Amitriptyline: 10 to 50 mg PO at bedtime to treat pain, fatigue, and sleep disturbances (13)[A]
  • Duloxetine: initially 30 mg/day for 1 week, then increase to 60 mg/day as tolerated. Taper if discontinued (13)[A].
  • Milnacipran: day 1: 12.5 mg/day; days 2 to 3, begin dividing doses: 12.5 mg BID; days 4 to 7: 25 mg BID; after day 7: 50 mg BID; max dose 100 to 200 mg BID. Taper if discontinued (13)[A].
  • Pregabalin: Start with 75 mg BID, titrate over 1 week to 150 mg BID; max dose 450 mg/day divided BID-TID (14)[A].
  • Cyclobenzaprine 5 mg HS; titrate up to 10 mg BID-TID (10)[B].
Second Line
  • Gabapentin start at 300 mg HS, titrate to 1,200 to 2,400 mg/day divided BID-TID (10)[B].
  • Fluoxetine 10 to 80 mg/day PO (higher doses may be more effective). Taper if discontinued (10)[B].
  • Paroxetine CR 12.5 to 62.5 mg/day. Taper if discontinued (10)[B].
  • Tramadol 50 to 100 mg q6h; likely more effective in combination with acetaminophen (10)[C]
  • Several investigational agents show some promise of benefit, including pramipexole (15), naltrexone, quetiapine, sodium oxybate (4), nabilone, and pirlindole (16)
  • Cholecalciferol may be beneficial in patients with low 25-OH vitamin D levels (17).
  • Medications likely to be ineffective (10)[C] include NSAIDs, opioids, benzodiazepines, magnesium, guaifenesin, thyroxine, corticosteroids, DHEA, melatonin, calcitonin; also antiepileptic agents (other than pregabalin and gabapentin) (18)[A].
  • Note that, given the frequent co-presentation of fibromyalgia with other pain syndromes, it may be reasonable to treat the latter with NSAIDs, corticosteroids, opioids, and other such agents in conjunction with evidence-based fibromyalgia therapies.
ISSUES FOR REFERRAL
In the case of unclear diagnosis or poor response to therapy, may refer to rheumatology, neurology, and/or pain management.
COMPLEMENTARY & ALTERNATIVE MEDICINE
  • Acupuncture (especially electroacupuncture), biofeedback, hypnotherapy (10,19)[B]
  • Balneotherapy (mineral-rich baths) (10)[B]
  • Yoga, tai chi, and qi gong—improve sleep, fatigue, and quality of life but may not decrease pain (20).
  • Limited double-blind trials have shown effectiveness of supplementation with S-adenosyl methionine, and acetyl-L-carnitine.
  • Transcranial direct current or magnetic stimulation and repetitive transcranial magnetic stimulation (21,22)
  • Likely to be ineffective: chiropractic treatment, massage, electrotherapy, ultrasound, trigger point injections (10)[A]
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • For efficacy of therapy at 2- to 4-week intervals
  • Advance exercise gradually to maintain tolerability
DIET
No proven efficacy of any specific diet. Caloric or carbohydrate restriction may be helpful in obese patients.
PROGNOSIS
  • 50% partial remission after 2 to 3 years of therapy (23)
  • Typically has fluctuating, chronic course
  • Poorer outcome tied to greater duration/severity of symptoms, depression, advanced age, lack of social support
REFERENCES
1. Jones GT, Atzeni F, Beasley M, et al. The prevalence of fibromyalgia in the general population: a comparison of the American College of Rheumatology 1990, 2010, and modified 2010 classification criteria. Arthritis Rheumatol. 2015;67(2):568-575.
2. Wolfe F, Häuser W. Fibromyalgia diagnosis and diagnostic criteria. Ann Med. 2011;43(7):495-502.
3. Smith HS, Harris R, Clauw D. Fibromyalgia: an afferent processing disorder leading to a complex pain generalized syndrome. Pain Physician. 2011;14(2):E217-E245.
4. Russell IJ, Holman AJ, Swick TJ, et al. Sodium oxybate reduces pain, fatigue, and sleep disturbance and improves functionality in fibromyalgia: results from a 14-week, randomized, double-blind, placebo-controlled study. Pain. 2011;152(5):1007-1017.
5. Arnold LM, Hudson JI, Hess EV, et al. Family study of fibromyalgia. Arthritis Rheum. 2004;50(3): 944-952.
6. Okifuji A, Donaldson GW, Barck L, et al. Relationship between fibromyalgia and obesity in pain, function, mood, and sleep. J Pain. 2010;11(12):1329-1337.
7. Boomershine CS, Emir B, Wang Y, et al. Simplifying fibromyalgia assessment: the VASFIQ Brief Symptom Scale. Ther Adv Musculoskelet Dis. 2011;3(5):215-226.
8. Bennett RM, Friend R, Marcus D, et al. Criteria for the diagnosis of fibromyalgia: validation of the modified 2010 preliminary American College of Rheumatology criteria and the development of alternative criteria. Arthritis Care Res (Hoboken). 2014;66(9):1364-1373.
9. Glass JM. Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions. Curr Rheumatol Rep. 2006;8(6):425-429.
10. National Guideline Clearinghouse. Guideline summary NGC-7367: management of fibromyalgia syndrome in adults. http://f.i-md.com/medinfo/material/8d0/4eb2854244ae46d1d13648d0/4eb2855d44ae46d1d13648d3.pdf. Accessed 2014.
11. Häuser W, Klose P, Langhorst J, et al. Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a systematic review and meta-analysis of randomised controlled trials. Arthritis Res Ther. 2010;12(3):R79.
12. Bidonde J, Busch AJ, Webber SC, et al. Aquatic exercise training for fibromyalgia. Cochrane Database Syst Rev. 2014;(10):CD011336.
13. Häuser W, Petzke F, Üçeyler N, et al. Comparative efficacy and acceptability of amitriptyline, duloxetine and milnacipran in fibromyalgia syndrome: a systematic review with meta-analysis. Rheumatology (Oxford). 2011;50(3):532-543.
14. Häuser W, Walitt B, Fitzcharles MA, et al. Review of pharmacological therapies in fibromyalgia syndrome. Arthritis Res Ther. 2014;16(1):201.
15. Holman AJ, Myers RR. A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. Arthritis Rheum. 2005;52(8):2495-2505.
16. Tort S, Urrútia G, Nishishinya MB, et al. Monoamine oxidase inhibitors (MAOIs) for fibromyalgia syndrome. Cochrane Database Syst Rev. 2012;(4):CD009807.
17. Wepner F, Scheuer R, Schuetz-Wieser B, et al. Effects of vitamin D on patients with fibromyalgia syndrome: a randomized placebo-controlled trial. Pain. 2014;155(2):261-268.
18. Wiffen PJ, Derry S, Moore RA, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia—an overview of Cochrane reviews. Cochrane Database Syst Rev. 2013;(11):CD010567.
19. Deare JC, Zheng Z, Xue CC, et al. Acupuncture for treating fibromyalgia. Cochrane Database Syst Rev. 2013;(5):CD007070.
20. Langhorst J, Klose P, Dobos GJ, et al. Efficacy and safety of meditative movement therapies in fibromyalgia syndrome: a systematic review and meta-analysis of randomized controlled trials. Rheumatol Int. 2013;33(1):193-207.
21. Marlow NM, Bonilha HS, Short EB. Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. Pain Pract. 2013;13(2):131-145.
22. Castillo-Saavedra L, Gebodh N, Bikson M, et al. Clinically effective treatment of fibromyalgia pain with high-definition transcranial direct current stimulation: phase II open-label dose optimization [published online ahead of print October 9, 2015]. J Pain.
23. Forseth KO, Førre O, Gran JT. A 5.5 year prospective study of self-reported musculoskeletal pain and of fibromyalgia in a female population: significance and natural history. Clin Rheumatol. 1999;18(2):114-121.
Additional Reading
&NA;
Theadom A, Cropley M, Smith HE, et al. Mind and body therapy for fibromyalgia. Cochrane Database Syst Rev. 2015;(4):CD001980.
See Also
&NA;
Algorithm: Fatigue
Codes
&NA;
ICD10
M79.7 Fibromyalgia
Clinical Pearls
&NA;
  • Use rigorous ACR criteria to make the diagnosis.
  • Fibromyalgia is not a somatoform disorder and is not merely a manifestation of depression or anxiety, although as with all chronic pain syndromes, it is frequently associated with mood disturbances.
  • Best outcomes occur in patients who understand their illness and are willing to actively engage in a multimodal treatment plan, including exercise, medication, CBT, and lifestyle modifications.