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Fibromyalgia is a common and chronic disorder of unknown etiology characterized by widespread pain and tenderness, abnormal pain processing, sleep disturbance, fatigue, and, often, psychological distress, as well as other symptoms.[1,2] Although fibromyalgia is frequently grouped with arthritis-related conditions, there is no apparent inflammation or damage to the joints, muscles, or other tissues.
Image courtesy of Medscape.
Data regarding the exact prevalence of fibromyalgia in the United States are limited. The estimated prevalence is 2%, affecting roughly 5 million adults (age ≥18 years), with women having a higher prevalence (3.4%) and incidence (80-90%) of this condition than men (0.5% and 10-20%, respectively).[1] Although fibromyalgia most typically presents to physicians in women of middle age, the onset of various pain symptoms often occurs early in life, and the condition can present in either sex at any age. Fibromyalgia leads to approximately 5.5 million ambulatory care visits per year, at an average total annual cost (direct and indirect) of $5945 per person. Direct medical costs among these patients primarily include office and emergency department visits, procedures and laboratory tests, and hospitalizations.
Data in image from Centers for Disease Control and Prevention.[1]
Multiple epidemiologic studies have demonstrated a strong genetic association with fibromyalgia.[3] Implicated genes include genes involved in the serotonin and catecholamine pathways. Alterations in either of these pathways could alter pain sensitivity. Additional genetic markers have been identified through genome-wide scans.
Adapted from Ablin JN et al.[3]
A biopsychosocial model of fibromyalgia provides a useful framework for organization. A number of biologic variables have been identified, including genetics, female sex, age, poor sleep, trauma, deconditioning, autonomic dysregulation, chronic infection, abnormal nociceptive processing, and stress. Identifiable psychological variables include hypervigilance, feelings of helplessness, poor coping strategies, depression, anxiety, certain personality traits and styles (eg, neuroticism, perfectionism, or compulsive behavior), and excessive pain behaviors. Environmental and sociocultural variables associated with fibromyalgia include family support, job satisfaction, childhood abuse, and family members or friends with chronic pain.
Image courtesy of Medscape.
The pathophysiologic sequence of events that leads to the development of fibromyalgia is not well elucidated; however, a number of discrete cellular and biochemical abnormalities have been identified. The volume of abnormalities discovered in patients with fibromyalgia is high enough to substantiate the claim that it is not a subjective pain condition. When viewed collectively, these abnormalities suggest that fibromyalgia is a disorder of central sensitization or abnormal central processing of nociceptive pain input.
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The pain associated with fibromyalgia is typically described as radiating diffusely from the axial skeleton over large areas of the body, predominantly involving the muscles and joints. Patients also present with various additional complaints. Fatigue and poor sleep are nearly universal, and most patients with fibromyalgia also meet the classification for chronic fatigue syndrome (CFS). Cognitive problems ("fibro fog") produce impairments in memory and thinking. Other, less commonly reported symptoms of fibromyalgia are shown in the slide. There is a significant amount of overlap among chronic pain disorders, central sensitivity syndromes (eg, CFS, irritable bowel syndrome [IBS], and posttraumatic stress disorder [PTSD]), and anxiety disorders. Systemic inflammatory illnesses (eg, rheumatoid arthritis, chronic hepatitis C, and systemic lupus erythematosus [SLE]) may be complicated by fibromyalgia. Patients with fibromyalgia typically suffer for many years before diagnosis and sometimes receive unnecessary, expensive, or needlessly invasive procedures or medication before fibromyalgia is recognized.
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A history of more than 3 months of diffuse musculoskeletal pain, along with the other symptoms mentioned in slide 6, suggests fibromyalgia. Physical examination is helpful in confirming the diagnosis. Except for heightened tenderness and evidence of deconditioning, the examination usually yields normal findings. A tender-point examination should be performed at the start of the physical examination. The 18 tender points (nine pairs) on the body, as designated by the American College of Rheumatology (ACR), are shown in the slide. The examiner places the thumb pad of his or her dominant hand on each point, pressing perpendicularly and gradually increasing pressure for 4 seconds to a pressure of 4 kg. The patient is asked whether or not there is pain and, if there is, to rate the pain on a scale of 0 to 10. A dolorimeter is sometimes used in clinical trials but is unnecessary in clinical practice.
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The 2010 ACR preliminary diagnostic criteria can be used to assist in the diagnosis of fibromyalgia (top).[1,4,5] (By current policy, the ACR no longer funds or endorses diagnostic criteria for rheumatic diseases.) Patients must also undergo a thorough clinical and laboratory evaluation to identify alternative or coexisting diagnoses for chronic pain. Although no diagnostic laboratory tests currently exist for fibromyalgia, appropriate initial studies include a workup to rule out hypothyroidism (thyroid-stimulating hormone [TSH]), inflammatory myopathies (creatine phosphokinase [CPK]), polymyalgia rheumatica (erythrocyte sedimentation rate [ESR]), lupus (antinuclear antibody [ANA]), and chronic infections (complete blood count [CBC] with differential). Depending on the constellation of presenting symptoms, sleep studies and joint fluid analysis may be helpful.
Table adapted from American College of Rheumatology.[4,5]
A 76-year-old white woman presents with the acute onset of disabling diffuse pain and stiffness involving both the pelvic girdle and the shoulder girdle. The pain is worst when she arises in the morning, improves as the day progresses, and worsens toward evening. She reports feeling feverish but has not checked her temperature. Her activity has been limited by pain. The patient was previously healthy except for Heberden nodes, for which she takes acetaminophen as needed. She has no joint swelling or rash. There is mild weakness of her shoulder girdle. There is no tenderness. Neurologic examination is normal. The CBC shows only a mild normocytic anemia. The ESR is 52 mm/hr.
Which of the following is the most likely diagnosis?
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Answer: D. Polymyalgia rheumatica.
Polymyalgia rheumatica is characterized by the acute onset of disabling pain and morning/rest stiffness involving both the upper half and the lower half of the body, along with an ESR higher than 50 mm/hr, which suggests that the pain has an inflammatory origin.[6] Patients are almost always older than 50 years. Shoulder-girdle weakness is often found, arising from disuse as a result of the pain. In view of the absence of tenderness and small-joint swelling, rheumatoid arthritis is unlikely. The symptoms suggestive of inflammatory pain and the ESR higher than 50 mm/hr are atypical for both fibromyalgia and osteoarthritis, rendering those diagnoses less likely as well.
Image courtesy of Sam Shlomo Spaeth / Medscape.[6]
A 76-year-old white woman presents with a 3-month history of diffuse pain involving both the upper half and the lower half of the body. She has a past history of trigeminal neuralgia, recurrent neck pain, and headaches. Her pain is mostly over soft tissue; it worsens throughout the day and is more severe after activity. On examination, the patient has no joint swelling or crepitus, but there is tenderness over multiple joints and bursae. No rash is visible. Neurologic examination yields normal results. Radiographs of the hands are normal; radiographs of the cervical spine show bone spurs. Magnetic resonance imaging (MRI) of the skull and brain shows normal findings, and MRI of the cervical spine shows bone spurs without spinal-cord compression. On laboratory evaluation, the patient has an ESR of 32 mm/hr and a low-titer positive test result for rheumatoid factor (RF).
Which of the following is the most likely diagnosis?
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Answer: D. Fibromyalgia.
The finding of diffuse pain and tenderness that persists throughout the day without joint swelling is consistent with fibromyalgia. Given that the ESR is lower than 50 mm/hr and the pain is typically worse in the morning, polymyalgia rheumatica is unlikely. Bone spurs in the cervical spine are frequently asymptomatic and are unlikely to be causing her symptoms in the absence of any evidence of spinal-cord or nerve-root compression. Osteoarthritis is also an unlikely cause in the absence of supportive findings on physical examination. New-onset rheumatoid arthritis should present with joint swelling in addition to pain. Whereas a low-titer positive RF test result is often found in patients with new-onset rheumatoid arthritis, it is also found in about 15% of elderly patients without rheumatoid arthritis.
Image courtesy of Medscape.
A 56-year-old white woman presents with diffuse muscle pain and progressive weakness of 3 months' duration. Her past history is negative for illnesses except for mild osteoarthritis in her knees, which she has had for several years. Examination reveals diffuse tenderness of proximal muscles in the shoulder girdle and pelvic girdle with muscle weakness that is worse in proximal muscles. Crepitus is palpated over both knees. No rash or joint swelling is observed, and neurologic examination yields normal results.
Which of the following is the most likely diagnosis?
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Answer: D. Polymyositis.
The finding of progressive proximal-muscle weakness suggests polymyositis. (The light micrograph in the slide shows a section of human muscle affected by polymyositis.) Although the diffuse pain and tenderness are consistent with fibromyalgia, the presence of progressive proximal-muscle weakness militates against that diagnosis. The absence of joint swelling and the presence of tenderness over muscles rather than over joints make both rheumatoid arthritis and osteoarthritis unlikely. Polymyalgia rheumatica is not typically associated with muscle tenderness or progressive muscle weakness.
Image by Steve Gschmeissner / Science Source.
Treatment for fibromyalgia is multifactorial and involves a multidisciplinary approach that includes psychological and behavioral therapy, physical therapy, and pharmacotherapy.[1,2,7,8] Achieving a satisfactory clinical response is difficult, but combination therapy has proved to be more effective than monotherapy. Nondrug therapy should be the primary treatment, with pharmacotherapy reserved for those who do not respond to nondrug therapy—namely, patient education, a carefully graded exercise program, and psychological and behavioral therapy. Psychological and behavioral therapy includes aggressive depression treatment, cognitive-behavioral therapy, operant-behavioral therapy, relaxation training, sleep hygiene, coping skills, and distraction strategies.
Table derived from CDC sources[1] and Medscape.[8]
Exercise has been proved to provide both subjective and objective improvements in pain and overall sense of well-being. Deconditioning is a major contributing factor to pain. Graded aerobic activity with aerobics (shown), aquatherapy, or stationary bicycles can be transitioned to more rigorous endurance and strength training. Heat and massage provide symptomatic relief for many forms of chronic pain, including fibromyalgia. Trigger-point injections, acupuncture, chiropractic manipulations, and myofascial release are not currently considered evidence-based approaches to therapy. All therapeutic approaches should emphasize self-sufficiency in pain control rather than reliance on others for symptomatic relief.
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Pharmacotherapy for fibromyalgia is complex and depends on the specific symptomatic profile of a given patient.[5] It is most effective when combined with nonpharmacotherapeutic strategies. A number of general principles are evident. Many patients with fibromyalgia are taking large doses of pain medications, but these agents have limited efficacy in fibromyalgia and should mainly be reserved for patients with concomitant nociceptive pain generators (eg, osteoarthritis). Narcotics should be avoided because they are both ineffective and potentially addicting. Aggressive treatment for comorbid depression and poor sleep is mandatory. Steroids are useful only for patients with coexisting inflammatory processes. Selective estrogen receptor modulators (SERMs) may be helpful for postmenopausal women. Identification of complementary and alternative medicine treatments used by patients is important to avoid potential drug-drug interaction.
Table adapted from American College of Rheumatology.[5]
A 56-year-old white woman reports experiencing "pain all over." The pain began 1 year ago in the neck and shoulder area and gradually spread to involve the hips, the pelvic area, and all four extremities, affecting muscles, bones, and joints. It was treated with a cervical collar and ibuprofen, neither of which afforded any significant benefit. The patient reports poor sleep with frequent awakening. Her pain worsens with activity. Her memory is poor. Her past history includes migraine headaches since adolescence and chronic gastrointestinal pain without a diagnosis. Findings from examination are normal except for diffuse tenderness over muscles, joints, and tendons with no joint swelling. No rash is observed. On laboratory evaluation, the ESR is 32 mm/hr, and test results are negative for RF and ANA.
Which of the following is the most likely diagnosis?
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Answer: E. Fibromyalgia.
Diffuse pain involving both the shoulder girdle and the pelvic girdle that worsens with activity and is not limited to muscles or joints is typical of fibromyalgia, as are disordered sleep, poor memory, and a history of other pain syndromes (eg, migraine headaches and functional bowel disorder). Diffuse small-fiber neuropathy can cause generalized pain but is not associated with the other features described, and it often gives rise to findings on neurologic examination. The pain of osteoarthritis worsens with use but is limited to joints and is unlikely to cause the broad pain distribution seen in this patient. In polymyositis, weakness is the most prominent symptom, and pain, if present, is limited to muscles. In polymyalgia rheumatica, stiffness and pain improve with activity, and the ESR is usually higher than 50 mm/hr.
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Answer: C. Amitriptyline 25 mg/day.
As mentioned previously, initial management of fibromyalgia should focus on nonpharmacologic therapy, including patient education, sleep management, cognitive therapy, and a graded education program. Analgesics and anti-inflammatory drugs (eg, naproxen) are generally ineffective. Concomitant depression should be treated, but such treatment alone will not improve fibromyalgia. If initial nonpharmacologic management does not improve the patient's symptoms, a medication that is effective against fibromyalgia should be added.
Image courtesy of Medscape.
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