Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain and tenderness. Although it is defined primarily as a pain syndrome, FM patients also commonly complain of associated neuropsychological symptoms of fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. Patients with FM have an increased prevalence of other syndromes associated with pain and fatigue, including chronic fatigue syndrome (Chap. 389), temporomandibular disorder, chronic headaches, irritable bowel syndrome, interstitial cystitis/painful bladder syndrome, and other pelvic pain syndromes. Available evidence implicates the central nervous system as key to maintaining pain and other core symptoms of FM and related conditions. The presence of FM is associated with substantial negative consequences for physical and social functioning.
FM is far more common in women than in men, with a ratio of about 9:1. In population-based studies worldwide, there is general agreement that the prevalence rate is approximately 2–3%, with rates of closer to 5–10% in primary care practices. The prevalence data are similar across socioeconomic classes. Cultural factors may play a role in determining whether patients with FM symptoms seek medical attention; however, even in cultures in which secondary gain is not expected to play a significant role, the prevalence of FM remains in this range.
The most common presenting complaint of a patient with FM is “pain all over.” Patients with FM have pain that is typically above and below the waist on both sides of the body and involves the axial skeleton (neck, back, or chest). The pain attributable to FM is poorly localized, difficult to ignore, severe in its intensity, and associated with a reduced functional capacity. Pain should have been present most of the day on most days for at least 3 months.
The clinical pain of FM is associated with increased evoked pain sensitivity. In clinical practice, this is determined by a tender point examination in which the examiner uses the thumbnail to exert pressure of approximately 4 kg/m2, or the pressure leading to blanching of the tip of the thumbnail, on well-defined musculotendinous sites (Fig. 335-1). American College of Rheumatology classification criteria previously required that 11 of 18 sites be perceived as painful for a diagnosis of FM. In practice, tenderness is a continuous variable, and strict application of a categorical threshold for diagnosis specifics is no longer necessary. Increased pain sensitivity can be demonstrated not only for the mechanical pressure-induced pain used in the clinic but also for nonmuscular mechanical pressure, heat, cold, and other sensory stimuli; this reinforces the idea that the pathogenic mechanisms of FM are not related to specific musculoskeletal pathology but to altered pain processing. New criteria eliminate tender points and focus on clinical symptoms of widespread pain and neuropsychological symptoms.
Tender point assessment in patients with fibromyalgia.
Patients with FM often have peripheral pain generators that are thought to serve as triggers for the more widespread pain attributed to central nervous system factors. Potential pain generators such as arthritis, bursitis, tendinitis, neuropathies, and other inflammatory or degenerative conditions should be identified by history and physical examination. More subtle pain generators may include joint hypermobility and scoliosis. Patients also may have chronic myalgias triggered by infectious, metabolic, or psychiatric conditions that can serve as triggers for the development of FM. These conditions are often in the differential diagnosis of patients with FM, and a major challenge is to distinguish the ongoing activity of a triggering condition from FM as a consequence of a comorbid condition that should itself be treated.
In addition to widespread pain, FM patients typically complain of fatigue, stiffness, sleep disturbance, cognitive dysfunction, anxiety, and depression. These symptoms are present to varying degrees in most FM patients but are not present in every patient or at all times. Such symptoms may, however, have an equal or even greater impact on function and quality of life. Fatigue is highly prevalent in patients under primary care who ultimately are diagnosed with FM. Pain, stiffness, and fatigue often are worsened by exercise or unaccustomed activity (postexertional malaise). The sleep complaints include difficulty falling asleep, difficulty staying asleep, and early-morning awakening. Regardless of the specific complaint, patients awake feeling unrefreshed. Patients with FM may meet criteria for restless legs syndrome and sleep-disordered breathing; frank sleep apnea can also be present. Cognitive complaints are characterized as slowness in processing, difficulties with attention or concentration, problems with word retrieval, and short-term memory loss. Studies have demonstrated altered cognitive function in these domains in patients with FM, though speed of processing is age-appropriate. Symptoms of anxiety and depression are common, and the lifetime prevalence of mood disorders in patients with FM approaches 80%. Although depression is neither necessary nor sufficient for the diagnosis of FM, it is important to screen for major depressive disorders by querying for depressed mood and anhedonia. Analysis of genetic factors that are likely to predispose to FM reveals shared neurobiologic pathways with mood disorders, providing the basis for comorbidity.
Because FM can overlap in presentation with other chronic pain conditions, review of systems often reveals headaches, facial/jaw pain, regional myofascial pain particularly involving the neck or back, and arthritis. Visceral pain complaints involving the gastrointestinal tract, bladder, and pelvic or perineal region are also often present. Patients may or may not meet defined criteria for specific syndromes. It is important for patients to understand that there may be shared pathways that mediate symptoms and that using treatment strategies effective for one condition may help with global symptom management.
FM is often comorbid with chronic musculoskeletal, infectious, metabolic, or psychiatric conditions. Whereas FM is present in only 2–5% of the general population, it occurs in 20% or more of patients with degenerative or inflammatory rheumatic disorders, probably because these conditions serve as peripheral pain generators to alter central pain-processing pathways. Similarly, chronic infectious, metabolic, or psychiatric diseases associated with musculoskeletal pain can mimic FM and/or serve as a trigger for the development of FM. It is particularly important for clinicians to be sensitive to pain management of these comorbid conditions so that when FM emerges, as characterized by pain outside the boundaries of what could reasonably be explained by the triggering condition, development of neuropsychological symptoms, or tenderness on physical examination, treatment of central pain processes will be undertaken rather than continuing to focus on treating peripheral or inflammatory causes of pain.
Symptoms of FM often have their onset and are exacerbated during periods of high levels of real or perceived stress. This may reflect an interaction between central stress physiology, vigilance or anxiety, and central pain-processing pathways. Understanding current psychosocial stressors will aid in patient management as many factors that exacerbate symptoms cannot be addressed by using pharmacologic approaches. Furthermore, there is a high prevalence of exposure to previous interpersonal and other forms of violence in patients with FM and related conditions. If posttraumatic stress disorder is an issue, the clinician should be aware of it and consider treatment options.
It is crucial to evaluate the impact of FM symptoms on function and role fulfillment. In defining the success of a management strategy, improved function is a key measure. Functional assessment should include physical, mental, and social domains. Understanding where role functioning falls short will assist in establishing treatment goals.
Because musculoskeletal pain is such a common complaint, the differential diagnosis of FM is broad. Table 335-1 lists some of the more common conditions that should be considered. Patients with inflammatory causes for widespread pain should be identifiable on the basis of specific history, physical findings, and laboratory or radiographic tests.
Table 335-1 Common Conditions in the Differential Diagnosis of Fibromyalgia |Favorite Table|Download (.pdf)
Table 335-1 Common Conditions in the Differential Diagnosis of Fibromyalgia
Inflammatory arthritis: rheumatoid arthritis, spondyloarthritides
Connective tissues diseases: systemic lupus erythematosus, Sjögren's syndrome
Human immunodeficiency virus (HIV)
Degenerative joint/spine/disk disease
Myofascial pain syndromes
Bursitis, tendinitis, repetitive strain injuries
Hypo- or hyperthyroidism
Neuropathic pain syndromes
|Major depressive disorder|
Laboratory or Radiographic Testing
Routine laboratory and radiographic tests are normal in patients with FM, and so diagnostic testing is focused on excluding other diagnoses and evaluating for pain generators or comorbid conditions (Table 335-2). Most patients with a new complaint of chronic widespread pain should be assessed for the most common entities in the differential diagnosis. Radiographic testing should be used sparingly and only for diagnosis of inflammatory arthritis. After the patient has been evaluated thoroughly, repeat testing is discouraged unless the symptom complex changes. Particularly to be discouraged is advanced imaging (MRI) of the spine unless there are features suggesting inflammatory spine disease or neurologic symptoms.
Table 335-2 Laboratory and Radiographic Testing in Patients with Fibromyalgia Symptoms |Favorite Table|Download (.pdf)
Table 335-2 Laboratory and Radiographic Testing in Patients with Fibromyalgia Symptoms
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
Complete blood count (CBC)
Complete metabolic panel
Thyroid-stimulating hormone (TSH)
|Guided by history and physical examination|
Antinuclear antibody (ANA)
Anti-SSA (anti-Sjögren's syndrome A) and anti-SSB
Rheumatoid factor and anticyclic citrullinated peptide (anti-CCP)
Creatine phosphokinase (CPK)
Viral and bacterial serologies
Spine and joint radiographs
As in most complex diseases, it is likely that a number of genes contribute to vulnerability to the development of FM. To date, these genes appear to be in pathways controlling pain sensitivity and stress response. Some of the genetic underpinnings of FM are shared across other chronic pain conditions. For example, catechol-O-methyltransferase, which controls the synaptic levels of norepinephrine and dopamine, has been associated with pain sensitivity in the general population and certain polymorphisms or haplotypes have been associated with FM, chronic fatigue syndrome, and temporomandibular disorder. Polymorphisms of the β-adrenergic receptor and dopamine receptor are also associated with FM and other chronic pain conditions. Genes associated with metabolism, transport, and receptors of serotonin and other monoamines have also been implicated in FM and overlapping conditions. Taken together, the pathways in which polymorphisms have been identified in FM patients further implicate central factors as mediating the physiology that leads to FM clinical manifestations.
Psychophysical testing of patients with FM has demonstrated altered sensory afferent pain processing and impaired descending noxious inhibitory control leading to hyperalgesia and allodynia. Functional MRI and other research imaging procedures clearly demonstrate activation of the brain regions involved in the experience of pain in response to stimuli that are innocuous in study participants without FM. Pain perception in FM patients is influenced by the emotional and cognitive dimensions, such as catastrophizing and perceptions of control, providing a solid basis for recommendations for cognitive and behavioral treatment strategies.
Approach to the Patient: Fibromyalgia
FM occurs commonly and has an extraordinary impact on functioning and health-related quality of life; however, symptoms and impact can be managed effectively by physicians and other health professionals. Developing a partnership with patients with a goal of understanding and implementing a treatment strategy and choosing appropriate nonpharmacologic and pharmacologic treatments are essential for improving the outcome of FM.
Patients with chronic pain, fatigue, and other neuropsychological symptoms require a framework for understanding the symptoms that have such an important impact on their function and quality of life. Providing explanation of the genetics, triggers, and physiology of FM can be an important adjunct in relieving the associated anxiety as well as reducing the overall cost of health care resources. In addition, patients must be educated regarding the expectations for treatment. The physician should focus on improved function and quality of life rather than elimination of pain. Illness behaviors should be discouraged, and behaviors that focus on improved function strongly encouraged.
Treatment strategies should include physical conditioning, with encouragement to begin at low levels of aerobic exercise with slow but consistent advancement. Patients who have been physically inactive or who report postexertional malaise may do best in supervised or water-based programs to start. Treatments that incorporate improved physical function with relaxation, such as yoga and Tai Chi, may also be helpful. Strength training may be recommended after a patient has reached his or her aerobic goals. Exercise programs are helpful for reductions in tenderness and for enhanced self-efficacy. Cognitive-behavioral strategies to improve sleep hygiene and reduce illness behaviors can also be helpful in management.
It is essential for the clinician to treat any comorbid triggering condition and clearly delineate for the patient the treatment goals for each medication. For example, glucocorticoids or nonsteroidal anti-inflammatory drugs may be useful for management of inflammatory triggers but are not effective for FM-related symptoms. At present, the treatment approaches that have proved most successful in FM patients target afferent or descending pain pathways. Table 335-3 outlines the drugs with demonstrated effectiveness. It should be emphasized strongly that opioid analgesics are to be avoided in patients with FM. These agents have no demonstrated efficacy in FM and are associated with opioid-induced hyperalgesia that can worsen both symptoms and function. Utilization of single agents to treat multiple symptom domains is strongly encouraged. For example, if a patient's symptom complex is dominated by pain and sleep disturbance, using an agent that exerts both analgesic and sleep-promoting effects is desirable. These agents include sedating antidepressants such as amitriptyline or alpha-2-delta ligands such as gabapentin and pregabalin. For patients with pain associated with fatigue, anxiety, or depression, drugs that have both analgesic and antidepressant/anxiolytic effects, such as duloxetine or milnacipran, may be the best first choice.
Table 335-3 Pharmacologic Agents Effective for Treatment of Fibromyalgia |Favorite Table|Download (.pdf)
Table 335-3 Pharmacologic Agents Effective for Treatment of Fibromyalgia
Antidepressants: balanced serotonin:norepinephrine reuptake inhibition
Anticonvulsants: ligands of the alpha-2-delta subunit of voltage-gated calcium channels