Fibromyalgia

CHAPTER 102

Fibromyalgia Joanne Borg-Stein, MD Michelle E. Brassil, MD Haylee E. Borgstrom, MD, MS

Synonym Fibrositis

ICD-10 Codes M79.7 M00–M99 M70-M79 M79

Fibromyalgia Diseases of the musculoskeletal system and connective tissue Other soft tissue disorders Other and unspecified soft tissue disorders, not elsewhere classified

Definition Fibromyalgia is a syndrome defined by chronic widespread pain of at least 3 months’ duration. It is a multisystem illness associated with neuropsychological symptoms including fatigue, stiffness, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. The majority of patients are women, for whom fibromyalgia is estimated to be three times more common than in men.1 The prevalence generally increases with age, with a peak prevalence rate in the fifth decade of life.2 A discrete etiology of fibromyalgia has not been identified. Available evidence implicates sensitization of the central and peripheral nervous systems as key in maintaining pain and other core symptoms of fibromyalgia.3–6 There may be a role for genetics, as individuals with certain genotypes are more likely to develop chronic pain and an overall increased sensitivity to pain during their lifetimes. These genes include catecholamine methyltransferase, sodium and potassium channels, and a number of others. Environmental factors, such as physical or emotional trauma, and infection (e.g., EpsteinBarr virus, Lyme disease, parvovirus), may interact with genetic factors to facilitate the development of fibromyalgia.6 Criteria for diagnosing fibromyalgia was first standardized by a multi-center study in 1990, which resulted in the American College of Rheumatology (ACR) 1990 classification criteria for fibromyalgia based on a tender point examination. This classification was later replaced by the 2010 ACR diagnostic criteria for fibromyalgia,7 which include the following: 1. Widespread pain index (WPI) score of at least 7 and a symptom severity scale (SSS) score of at least 5, or a WPI score of at least 3 and an SSS score of at least 9.

2. Symptoms present at a similar level for at least 3 months. 3.  The patient must not have another disorder that would otherwise explain the pain. The 2010 criteria were modified in 2011, allowing the diagnosis to be made by patient self-report for the purpose of research, and most recently, a 2016 revision to the 2010/2011 criteria has been proposed by Wolfe et al. (Table 102.1), which combines the physician and patient questionnaire, minimizes misclassification of regional pain disorders, and eliminates the recommendation regarding diagnostic exclusions. The 2016 criteria include: 1. WPI score of at least 7 and SSS score of at least 5 or WPI of 4–6 and SSS score of at least 9. 2. Generalized pain, defined as pain in at least 4 of 5 regions, must be present. Jaw, chest, and abdominal pain are not included in the generalized pain definition. 3. Symptoms have been generally present for at least 3 months. 4. A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses. Also developed with the 2016 revisions is the fibromyalgia severity scale, which is the sum of the WPI and SSS, ranging from 0 (no symptoms) to 31 (most severe symptoms). This score can help monitor improvement.8 

Symptoms Fibromyalgia is characterized by widespread and long-lasting pain (>3 months) located above and below the waist, on both sides of the body. A series of other symptoms are frequently reported by patients. These include marked fatigue, stiffness, sleep disorders, cognitive disturbances (e.g., concentration difficulties, forgetfulness, decreased comprehension), anxiety, depression, temporomandibular joint syndrome, paresthesias, headaches, genitourinary manifestations (e.g., interstitial cystitis, chronic prostatitis, vulvodynia), irritable bowel syndrome, and orthostatic intolerance.4 

Physical Examination Even though the general medical examination of a patient with fibromyalgia should be normal, a thorough physical examination remains vital. One study found that of patients referred to a rheumatologist for suspected fibromyalgia, a diagnosis of inflammatory or degenerative arthritis or soft tissue rheumatism was missed by the referring physician in 45% 555

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Table 102.1  2016 Revised Fibromyalgia Criteria Fibromyalgia Criteria—2016 Revision A patient satisfies modified 2016 fibromyalgia criteria if the following conditions are met: 1. WPI ≥7 and SSS score ≥5 OR WPI of 4–6 and SSS score ≥ 9. 2. Generalized pain, defined as pain in at least 4 of 5 regions, must be present. Jaw, chest, and abdominal pain are not included in generalized pain definition. 3. Symptoms have been generally present for at least 3 months. 4. A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses. WPI (score 0–19, 1 point for each location) Region 1: Left upper region Region 2: Right upper region Jaw, left

Jaw, right

Shoulder girdle, left

Shoulder girdle, right

Upper arm, left

Upper arm, right

Lower arm, left

Lower arm, right

Region 3: Left lower region

Region 4: Right lower region

Hip (buttock, trochanter), left

Hip (buttock, trochanter), right

Upper leg, left

Upper leg, right

Lower leg, left

Lower leg, right

Region 5: Axial region Neck Upper back Lower back Chest Abdomen SSS (total score, between 0 and 12) SSS Part 1 (each symptom is rated 0–3, 0 = no problem, 1 = slight/ mild/intermittent, 2 = moderate/frequent, 3 = severe/pervasive/ continuous) SSS Part 2 (1 point for each symptom the patient has been bothered by over the previous 6 months) Fatigue Headaches Waking unrefreshed Pain or cramps in lower abdomen Cognitive symptoms Depression SSS, Symptom severity scale; WPI, widespread pain index. Data from Wolfe F, Clauw D, Walitt B, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46:319–329.

of cases. Blood pressure recording for orthostatic hypotension should be performed, as patients with fibromyalgia show an increased prevalence of neurally mediated hypotension during tilt table testing.9 Evaluation of mood and affect is important since patients with fibromyalgia have a lifetime prevalence of mood disorders, mostly major depression, ranging between 20% and 86%.9 As mentioned earlier, a tender point exam is no longer a part of the diagnostic criteria; however, patients with fibromyalgia are not exempt from having superimposed regional myofascial pain associated with trigger points. Trigger points are hyperirritable spots in the fascia surrounding skeletal

muscle.10 The painful point can be felt as a nodule or band in the muscle, and a twitch response can be elicited on stimulation of the trigger point.10 It is crucial to identify trigger points on examination since specific interventions are available (see Procedures section). Recognizing and treating myofascial pain and other common musculoskeletal pathology, like bursitis, tendinitis, radiculopathy, etc., helps isolate the pain secondary to fibromyalgia and better understand its response to treatment. 

Functional Limitations Patients are limited in their daily activities and exercise tolerance by both pain and fatigue. A large portion of patients also report cognitive dysfunction. This has been termed “fibro fog.” Studies have found that cognitive inhibition, which is the ability to focus despite distractions, is consistently impaired in fibromyalgia patients, as is working memory, compared to healthy controls. It has been hypothesized that cognitive dysfunction in fibromyalgia arises because brain resources used for pain processing are not available for cognitive tasks.9 Approximately 25% of patients with fibromyalgia report themselves as disabled and are collecting some form of disability payment. Individuals are more likely to become disabled if they report higher pain scores, work at a job that requires heavy physical labor, have poor coping strategies and feel helpless, or are involved in litigation.11-13 

Diagnostic Studies Fibromyalgia is a clinical diagnosis. For other conditions to be excluded, basic laboratory tests may be appropriate, such as complete blood count, erythrocyte sedimentation rate, thyroidstimulating hormone concentration, liver transaminases, and creatine kinase activity. Primary sleep disorders may need to be identified by sleep studies. Radiography or magnetic resonance imaging may be indicated if osteoarthritis, radiculopathy, spinal stenosis, or intrinsic joint disease is suspected. Electrodiagnostic studies may be useful to rule out an entrapment neuropathy or radiculopathy. There is a growing body of literature demonstrating that many patients with fibromyalgia also carry the diagnosis of small fiber neurop­ athy. The meaning of this remains unclear, however, as small fiber neuropathy has been found in other conditions that are not accompanied by widespread pain.14  Differential Diagnosis Thyroid myopathy Metabolic myopathy Rheumatic disease Lyme disease Neuropathies Mood and sleep disturbances Somatoform pain disorders Myofascial pain syndrome

Treatment Initial Initial treatment includes patient education, gentle exercise, relaxation training, and consideration of pharmacologic

CHAPTER 102 Fibromyalgia

intervention. A stepwise, multidisciplinary, shared decision-making approach to fibromyalgia management is recommended. After making the clinical diagnosis, the first step is to provide information regarding the syndrome, its prognosis, and potential interventions. Emphasis should be placed on the importance of sleep, exercise, and stress reduction.15 Patient education itself has been shown to have a therapeutic effect and can include both individual and group classes to review the symptoms of fibromyalgia, emphasize the importance of adhering to a treatment program, and create a sense of community. Reassurance as to the generally benign course, as well as an outline of the treatment plan, should be provided.16-20 Additionally, treatment of comorbid conditions, such as mood or sleep disturbances, should be initiated. The second step is to integrate non-pharmacologic and, when indicated, pharmacologic treatment strategies with emphasis on an individualized treatment plan. The patient should begin a cardiovascular exercise program and be referred for cognitive-behavioral therapy (CBT). Trials of medications including serotonin and norepinephrine reuptake inhibitors, anticonvulsants, or tricyclic antidepressants should be considered, particularly for patients with refractory symptoms or certain medical comorbidities. The third step is consideration of specialty referral to rheumatology, physiatry, neurology, psychiatry, or pain management for those patients in which diagnosis is not certain or symptoms are refractory.15 Pharmacologic management of fibromyalgia is not required and should be used as an adjunct to non-pharmacologic methods aimed at normalizing sleep patterns, reducing fatigue, and diminishing pain. Current first-line agents include pregabalin, duloxetine, milnacipran, and amitriptyline—all of which provide only modest benefit.15,21-23 The typical number needed to treat to achieve at least 50% pain reduction ranges from 5 to 10.15,21-23 Thus combination therapies are frequently utilized. Greater benefit can be achieved with thoughtful medication selection aimed at treating specific comorbid conditions. For example, duloxetine is preferred for patients with comorbid depression, pregabalin or amitriptyline for comorbid sleep disturbances, and pregabalin or duloxetine for comorbid anxiety.15 Medications should be started at low doses with gradual up-titration based on tolerability. Recommended starting doses and highest recommended doses for treatment of fibromyalgia are as follows: amitriptyline 10 mg nightly, up to 50 mg nightly; pregabalin 50 mg nightly, up to 225 mg twice daily; duloxetine 30 mg daily, up to 60 mg daily; and milnacipran 12.5 mg daily with titration to 50 mg twice daily, up to 100 mg twice daily. Higher doses may be recommended for treatment of comorbid medical conditions.21-23 Second-line treatment options include gabapentin, cyclobenzaprine, selective serotonin reuptake inhibitors (e.g., fluoxetine, paroxetine), and tramadol either alone or with acetaminophen.15,21,24,25 Tramadol can be considered in those with comorbid rheumatic disease or advanced osteoarthritis. The use of other medications, such as low-dose naltrexone, cannabinoids, and quetiapine, is still considered experimental.21 Few high-quality direct comparison or combination studies have been completed. In general, medications can be expected to provide at least 30% pain reduction in half of patients and at least 50% pain reduction in a third of patients, though pain relief itself

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does not necessarily correspond to improved function or perceived well-being.21 Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids is not recommended for the treatment of fibromyalgia. Chronic NSAID use can lead to increased risk of cardiovascular and gastrointestinal side effects,26,27 and chronic opioid use can lead to development of opioid-induced hyperalgesia among other detrimental effects to both the individual and society as a whole.15 Ideally, fibromyalgia would be managed with little to no medication, given only modest efficacy and frequent side effects. Long-term symptom reduction leading to improved function is rarely achieved without optimizing patient education, psychologic well-being via CBT, and exercise, all of which are supported by level 1A evidence. The overall efficacy and sustained benefit for these cost-effective and low-risk interventions often exceeds that achieved with pharmacologic treatment.15 Additional non-pharmacologic pain control methods include acupuncture, trigger point injections, myofascial release therapy, chiropractic manipulation, massage, aqua therapy, yoga, thai chi, and biofeedback.6,28-30 

Rehabilitation Physical therapy is used to provide the patient with a stretching, gentle strengthening, and cardiovascular fitness program. The aerobic exercise prescription includes lowimpact interventions, such as walking and swimming, with gradual increase from low-intensity to moderate-intensity exercise.16 This can improve fitness and function, as well as decrease pain. Occupational therapy is incorporated to review ergonomics and activities of daily living at the work site. Task simplification, pacing, and maximization of function are emphasized.31-34 Mental health professionals can be helpful in the rehabilitative phase to educate patients in a mind-body stress reduction program, which may include CBT, relaxation, and biofeedback. Mindfulness-based stress reduction has been shown to decrease perceived stress, sleep disturbance, and perception of illness burden.35 Guided imagery and hypnosis have been shown to reduce pain and psychological distress. Hypnosis combined with CBT may have benefit over CBT alone.36 The goal of many of these interventions is to provide the patient with positive coping mechanisms for living with chronic pain.19,37,38 Associated depression and anxiety often need psychopharmacologic treatment. 

Procedures Myofascial trigger points may be injected with 1% lidocaine to decrease local pain and to increase pain thresholds.15,39 Patients with recalcitrant chronic myofascial pain may respond to injections with botulinum toxin.40 Dry needling is a broad term used to differentiate ‘‘noninjection’’ needling from the practice of ‘‘injection needling.’’ In contrast to injection of an agent, as in trigger point injections, dry needling utilizes a solid filament needle, and relies on the stimulation of specific reactions in the target tissue for its therapeutic effect.41 Evidence supports the use of dry needling in fibromyalgia patients; however, it is unclear how

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long the improvements in pain and fatigue last. Thus, the optimal frequency of dry needling is undetermined.41 If patients have concurrent bursitis, tendinitis, or nerve entrapment, therapeutic injections may be performed to treat these specific diagnoses. Acupuncture can be used for treatment of pain and fatigue. Research suggests that the benefit may last up to several months but is likely to wane over time. Treatment two times weekly for at least six visits appears necessary. The optimal number and frequency of acupuncture treatments have not been determined.2,42-44 

Surgery There is no surgery indicated for fibromyalgia. 

Technology There is no specific technology for the treatment or rehabilitation of this condition. 

Potential Disease Complications Failure to make an early diagnosis may lead to delay in treatment, deconditioning, and expensive, unnecessary medical testing and procedures. Chronic intractable pain may occur despite treatment. 

Potential Treatment Complications Because only a minority of patients will achieve meaningful pain relief with pharmacologic intervention, it is important to continuously evaluate for adverse medication effects. Tricyclic antidepressant medications can be associated with anticholinergic side effects, such as urinary retention, sedation, constipation, and weight gain. Pregabalin may lead to sedation, dizziness, peripheral edema, and weight gain. Selective serotonin reuptake inhibitor medications may be associated with sexual dysfunction, gastrointestinal intolerance, and anorexia. Additionally, they carry a black box warning for increased suicidal tendency in young adults with major depression.25 The threshold for seizures is lowered by tramadol. In addition, the risk for seizure is enhanced by the concomitant use of tramadol with selective serotonin reuptake inhibitors.45 Overly aggressive exercise programs may transiently increase pain in some patients. Injections may result in local pain, ecchymosis, intravascular injection, or pneumothorax if they are improperly executed.

References 1. Queiroz L. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep. 2013;17(8):356. 2. Walitt B, Nahin R, Katz R, Bergman M, Wolfe F. The prevalence and characteristics of fibromyalgia in the 2012 national health interview survey. Plos One. 2015;10(9):e0138024. 3. Bennett R. Fibromyalgia: present to future. Curr Rheumatol Rep. 2005;7:371–376. 4. Goldenberg DL. Diagnosis and differential diagnosis of fibromyalgia. Am J Med. 2009;122:S14–S21. 5. Staud R. Abnormal pain modulation in patients with spatially distributed chronic pain: fibromyalgia. Rheum Dis Clin North Am. 2009;35:263–274. 6. Goldenberg DL, Clauw DJ, Fitzcharles MA. New concepts in pain research and pain management of the rheumatic diseases. Semin Arthritis Rheum. 2011;41:319–334.

7. Wolfe F, Clauw DJ, Fitzcharles M, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. 2010;62:600–610. 8. Wolfe F, Clauw D, Walitt B, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. [serial online]. 2016;46:319–329. 9. Borchers A, Gershwin M. Fibromyalgia: a critical and comprehensive review. Clin Rev Allergy Immunol. 2015;49(2):100. 10. Travell J, Simons D, Simons L. Myofascial Pain and Dysfunction: The Trigger Point Manual, 2nd ed. Vol 2. Baltimore: Lippincott Williams & Williams; 1999. 11. Bennett RM. Fibromyalgia and the disability dilemma. Arthritis Rheum. 1996;19:1627–1633. 12. Kurtze N, Gundersen KT, Svebak S. The impact of perceived physical dysfunction, health-related habits, and affective symptoms on employment status among fibromyalgia support group members. J Musculoskel Pain. 2001;9:39–53. 13. Henriksson CM, Liedberg GM, Gerdle B. Women with fibromyalgia: work and rehabilitation. Disabil Rehabil. 2005;27:685–695. 14. Clauw D. 1: Diagnosing and treating chronic musculoskeletal pain based on the underlying mechanism(s). Best Pract Res Clin Rheumatol [serial online]. 2015;29:6–19. 15. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311(15): 1547–1555. 16. Wilson B, Spencer H, Kortebein P. Exercise recommendations in patients with newly diagnosed fibromyalgia. PM R. 2012;4:252–255. 17. Dadabhoy D, Clauw DJ. Fibromyalgia: progress in diagnosis and treatment. Curr Pain Headache Rep. 2005;9:399–404. 18. Borg-Stein J. Treatment of fibromyalgia, myofascial pain and related disorders. Phys Med Rehabil Clin N Am. 2006;17:491–510. 19. Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. 2004;292:2388–2395. 20. Arnold LM, Clauw DJ, Dunegan LJ, Turk DC. A framework for fibromyalgia management for primary care providers. Mayo Clin Proc. 2012;87:488–496. 21. Häuser W, Walitt B, Fitzcharles M, Sommer C. Review of pharmacological therapies in fibromyalgia syndrome. Arthritis Res Ther. 2014;16:201. 22. 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. 23. Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;(1):CD007115. 24. Moldofsky H, Harris HW, Archambault WT, et al. Effects of bedtime very low dose cyclobenzaprine on symptoms and sleep physiology in patients with fibromyalgia syndrome: a double-blind randomized placebocontrolled study. J Rheumatol. 2011;38:2653–2663. 25. Walitt B, Urrútia G, Nishishinya MB, Cantrell SE, Häuser W. Selective serotonin reuptake inhibitors for fibromyalgia syndrome. Cochrane Database Syst Rev. 2015;(6):CD011735. 26. Mansour A, Perace M, Johnson B, et al. Which patients taking SSRIs are at greatest risk of bleeding? J Fam Pract. 2006;55:206–208. 27. Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342. c7086. 28. Wang C, Schmid CH, Rones R, et al. A randomized trial of tai chi for fibromyalgia. N Engl J Med. 2010;363:743–754. 29. Carson JW, Carson KM, Jones KD, et al. A pilot randomized controlled trial of the yoga of awareness program in the management of fibromyalgia. Pain. 2010;151:530–539. 30. Mist SD, Firestone KA, Jones KD. Complementary and alternative exercise for fibromyalgia: a meta-analysis. J Pain Res. 2013;6:247–260. 31. Gowans SE, deHueck A, Voss S, Richardson M. A randomized, controlled trial of exercise and education for individuals with fibromyalgia. Arthritis Care Res. 1999;12:120–128. 32. Rosen NB. Physical medicine and rehabilitation approaches to the management of myofascial pain and fibromyalgia syndromes. Baillieres Clin Rheumatol. 1994;8:881–916. 33. Kingsley JD, Panton LB, Toole T, et al. The effects of a 12-week strength-training program on strength and functionality in women with fibromyalgia. Arch Phys Med Rehabil. 2005;86:1713–1721. 34. Tomas-Carus P, Gusi N, Häkkinen A, et al. Eight months of physical training in warm water improves physical and mental health in women with fibromyalgia: a randomized controlled trial. J Rehabil Med. 2008;40:248–252.

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35. Cash, et al. Mindfulness meditation alleviates fibromyalgia symptoms in women: results of a randomized clinical trial. Ann Behav Med. 2015;49:319–330. 36.  Zech, et al. Guided imagery/hypnosis in fibromyalgia. Eur J Pain. 2017;21:217–222. 37. Kaplan KH, Goldenberg DL, Galvin-Nadeau M. The impact of a meditation-based stress reduction program on fibromyalgia. Gen Hosp Psychiatry. 1993;15:284–289. 38. Glombiewski JA, Sawyer AT, Gutermann J, et al. Psychological treatments for fibromyalgia: a meta-analysis. Pain. 2010;151:280–295. 39. Affaitati G, Costantini R, Fabrizio A, et al. Effects of treatment of peripheral pain generators in fibromyalgia patients. Eur J Pain. 2011;15:61–69. 40. Göbel H, Heinze A, Reichel G, et al. Dysport myofascial pain study group. Efficacy and safety of a single botulinum type A toxin complex treatment for the relief of upper back myofascial pain syndrome: results from a randomized double-blind placebo-controlled multicentre study. Pain. 2006;125:82–88.

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41. Casanueva B, Rivas P, Rodero B, Quintial C, Llorca J, GonzálezGay M. Short-term improvement following dry needle stimulation of tender points in fibromyalgia. Rheumatol Int [serial online]. 2014;34(6):861–866. 42. Mayhew E, Ernst E. Acupuncture for fibromyalgia—a systematic review of randomized clinical trials. Rheumatology (Oxford). 2007;46:801–804. 43. Targino RA, Imamura M, Kaziyama HHS, et al. A randomized controlled trial of acupuncture added to usual treatment for fibromyalgia. J Rehabil Med. 2008;40:582–588. 44. Amezaga Urruela M, Suarez-Almazor ME. Acupuncture in the treatment of rheumatic diseases. Curr Rheumatol Rep. 2012;14:589–597. 45. Gardner JS, Blough D, Drinkard CR, et al. Tramadol and seizures: a surveillance study in a managed care population. Pharmacotherapy. 2000;20:1423–1431.