INTRODUCTION ? Fibromyalgia is a common cause of chronic musculoskeletal pain. It is one of a group of soft tissue pain disorders that affect muscles and soft tissues such as tendons and ligaments. None of these conditions is associated with tissue inflammation and the etiology of the pain is not known.
Despite the fact that each of these conditions is very common, they are also controversial. Patients look well, there are no obvious abnormalities on physical examination, and laboratory and radiologic studies are normal. Thus, the role of organic illness has been questioned and such disorders have often been considered to be psychogenic or psychosomatic in nature.
Fibromyalgia, initially termed fibrositis, was described in France and England in the mid-nineteenth century. By the end of the twentieth century, many rheumatologistsrecognized fibromyalgia as a discrete syndrome. Diagnostic classification criteria were proposed, evaluated, and then validated. Using such criteria, fibromyalgia is now considered to be the most common cause of generalized, musculoskeletal pain in women between ages of 20 and 55 years; in the United States, the prevalence is approximately two percent and increases with age [1-3].
The clinical manifestations and diagnosis of fibromyalgia will be reviewed here. Evidence regarding possible pathogenic mechanisms and a detailed discussion of treatment are presented separately. (See "Pathogenesis of fibromyalgia" and see "Treatment of fibromyalgia in adults").
The clinical manifestations, diagnosis, and treatment of fibromyalgia in children and adolescents is also presented separately. (See "Fibromyalgia in children and adolescents").
CLINICAL MANIFESTATIONS ? Fibromyalgia is 10 times more common in females. The prevalence of this disorder in the community increases with age from two percent at age 20 to eight percent at age 70; most patients present between the ages of 30 and 55 [4]. In approximately one-half of cases, the symptoms appeared to begin after a specific event, most often some form of physical or emotional trauma or a flu-like illness.
The cardinal manifestation of fibromyalgia is diffuse musculoskeletal pain (show figure 1). Although the pain may initially be localized, often in the neck and shoulders, it eventually involves many muscle groups. Patients typically complain of axial pain in the neck, middle, and lower back, and pain in the chest wall, arms, and legs. The pain is chronic and persistent, although it usually varies in intensity. Patients often have difficulty distinguishing joint and muscle pain and also may report a sensation of swelling; however, the joints do not appear swollen or inflamed on examination. Pain is often aggravated by exertion, stress, lack of sleep and weather changes. Sensations of numbness, tingling, burning, or a crawling sensation are often described.
Patients also may have a variety of poorly understood pain symptoms, including abdominal and chest wall pain and symptoms suggestive of irritable bowel syndrome, pelvic pain and bladder symptoms of frequency and urgency suggestive of the female urethral syndrome or of interstitial cystitis [5].
Fatigue is present in more than 90 percent of cases and is occasionally the chief complaint. Most patients report light sleep and feeling unrefreshed in the morning, while others report symptoms suggestive of pathologic sleep disturbances such as sleep apnea or nocturnal myoclonus. In addition, light-headedness, dizziness, and feeling faint are common symptoms. Mood disturbances (especially depression, anxiety, and heightened somatic concern), cognitive dysfunction (such as short term memory loss), and headaches (either muscular or migraine-type) are also frequent complaints.
Additional symptoms and clinical manifestations may include complaints of ocular dryness, multiple chemical sensitivity and "allergic" symptoms, dysphagia, palpitations, dyspnea, vulvodynia, dysmenorrhea, nondermatomal paresthesias, osteoporosis, weight fluctuations, night sweats, dysphagia, dysgeusia, glosodynia, and weakness [5-8].
The only helpful finding on physical examination is excessive tenderness. This excess tenderness is best determined by palpation of predefined muscle and tendon insertions, termed tender points (show figure 2). These tender points are usually bilateral and symmetrically tender. However, patients with fibromyalgia are more tender than healthy controls at any musculoskeletal site.
Aside from tenderness, the musculoskeletal examination is unremarkable and there is no evidence to indicate a systemic connective tissue or neurologic disease, unless the patient has an associated illness. As an example, fibromyalgia may occur concurrently with any rheumatic disorder, including rheumatoid arthritis, osteoarthritis, and systemic lupus erythematosus.
CLASSIFICATION CRITERIA ? A number of classification criteria for the diagnosis of fibromyalgia have been proposed. In 1990, the largest diagnostic criteria study, under the auspices of the American College of Rheumatology, enrolled 293 fibromyalgia patients and 265 patients with chronic rheumatic disorders such as low back pain, neck and arm pain, osteoarthritis, and rheumatoid arthritis [9]. These controls were selected, since they would be most difficult to distinguish from patients with fibromyalgia. Over 300 variables, including symptoms, physical findings, and laboratory and radiologic studies, were analyzed. The recommended diagnostic criteria were quite simple:
Widespread musculoskeletal pain
Excess tenderness in at least 11 of 18 predefined anatomic sites (show figure 2).
Requiring both criteria to be present results in 80 percent sensitivity and specificity in differentiating patients with fibromyalgia from controls with other chronic painful disorders. No exclusionary criteria were proposed.
Satisfying both criteria is particularly important in clinical studies to assure homogeneity of patients. These criteria have been validated in broad-based population studies and are highly reliable. However, in practice, a patient may be diagnosed with fibromyalgia without having the recommended number of tender points. Furthermore, this criteria may be considered subjective, since both are based on patient report. Unfortunately, there is no gold standard, such as a histologic tissue change or a laboratory measure of disease activity.
DIAGNOSIS ? The clinical diagnosis of fibromyalgia is based largely upon the patient's history of chronic, generalized pain and associated features, including fatigue, sleep disturbances, headache, cognitive difficulty, and mood disturbances.
Physical examination ? A thorough general physical examination is valuable to assess for concomitant disorders. A general musculoskeletal examination and neurologic examination should be routinely performed to help exclude any obvious arthritis, connective tissue disorder, or neurologic condition.
Tender point examination ? To establish the diagnosis, the tender point examination noted above should always be done in the same fashion, applying pressure equivalent to about 4 kg/cm to selected anatomic locations (show figure 2). This can be accurately measured with a dolorimeter or estimated by palpation with a finger. Applying enough pressure to whiten the examiner's fingernail bed generates approximately 4 kg/cm of pressure [10]. The pressure should be applied gradually over a few seconds and to both right and left sides of the body. Control locations, such as over the thumbnail or the mid-forearm, should also be examined and should not be as tender as the predefined tender points.
Laboratory testing ? Many patients have previously undergone multiple laboratory and radiologic studies, which are unrevealing. If a patient has not been previously evaluated, initial laboratory testing should include a complete blood count, erythrocyte sedimentation rate, thyroid function tests, and muscle enzymes.
More extensive laboratory testing is unnecessary and will often provide confusing results. For example, the prevalence of elevated antinuclear antibody levels in otherwise healthy persons is substantial. Thus the predictive value of a positive antinuclear antibody test in a patient without characteristic symptoms and signs of systemic lupus erythematosus (SLE) is low. Too often, patients with fibromyalgia are told that they may have SLE or another connective tissue disease based upon inappropriate use of such laboratory tests. (See "Measurement and clinical significance of antinuclear antibodies", section on False positives).
DIFFERENTIAL DIAGNOSIS ? The multiple nonspecific symptoms of fibromyalgia can mimic many other conditions. As examples, pain localized to the chest wall may suggest cardiac disease, whereas pain in the abdominal or pelvic muscles can mimic gastrointestinal or genitourinary disease. Similar confusion can occur with paresthesias and the Raynaud phenomenon. Myalgias and the perception of muscle weakness may suggest an inflammatory muscle disease or a metabolic myopathy. The broad differential diagnosis of fibromyalgia is presented separately. (See "Differential diagnosis of fibromyalgia").
COEXISTING DISORDERS ? Coexisting connective tissue diseases, psychiatric illnesses, sleep disorders, and chronic infections complicate the assessment of patients with pain and tenderness that meets criteria for classification as fibromyalgia. Overlap between symptoms of fibromyalgia and other diseases of unknown etiology, such as chronic fatigue syndrome, further complicating efforts at classification and diagnosis.
Connective tissue disease ? Since fibromyalgia may develop in patients with rheumatic or systemic illness, it may be difficult to determine whether a patient's symptoms are related to that associated illness or to fibromyalgia. The history is often helpful in this regard. Suppose that a patient with chronic but inactive rheumatoid arthritis complains of diffuse pain and fatigue but has no active synovitis and a normal ESR. In this setting, it is worthwhile to consider fibromyalgia as a cause of those symptoms, rather than escalating or reinstituting therapy for rheumatoid arthritis.
Psychiatric illness ? Approximately 30 percent of patients with fibromyalgia have major depression or anxiety disorders [11]. Indeed, in some patients mood and cognitive problems are much more prominent than tenderness [12]. However, the majority of patients with fibromyalgia do not have any current psychopathology and patients rarely meet diagnostic criteria for somatization disorders. Nevertheless, a careful psychiatric evaluation is often very useful. (See "Depression in adults: Pathophysiology, clinical manifestations, and diagnosis").
Sleep disorders ? The constellation of a sleep disorder, fatigue, and diffuse pain may also be observed in some patients with sleep apnea and the restless leg syndrome. The ability to distinguish among these sleep disorders is important, since their therapy is quite different from that of the sleep disorder associated with fibromyalgia. (See "An overview of obstructive sleep apnea: Epidemiology, pathophysiology, clinical presentation, and treatment in adults" and see "Restless legs syndrome").
Infectious diseases ? Chronic pain and tenderness typical of fibromyalgia are also present in some patients with chronic viral or bacterial infections.
Hepatitis C ? The prevalence of fibromyalgia in patients with ongoing infection with hepatitis C is moderately increased compared to that in the general population. Five percent of infected patients met criteria for fibromyalgia in one study of 77 such patients [13]. A history of exposure to blood products, illicit injection drug use, or high risk sexual behavior may identify patients at risk of hepatitis C infection, many of whom are also rheumatoid factor positive. (See "Clinical features and natural history of hepatitis C virus infection").
Lyme disease ? Fibromyalgia can also be triggered by Lyme disease. Furthermore, persistent symptoms of pain and fatigue may reflect fibromyalgia rather than persistent infection. This issue is discussed elsewhere. (See "Diagnosis and mechanisms of persistent Lyme disease", section on Misdiagnosis of chronic Lyme disease).
Other disorders of uncertain etiology ? Fibromyalgia also overlaps with other poorly understood syndromes, especially chronic fatigue syndrome (CFS), myofascial pain, and temporomandibular joint syndrome (show table 1) [14].
Chronic fatigue syndrome ? Operational diagnostic criteria for the classification of CFS are similar to those for fibromyalgia and studies have demonstrated that the majority of patients with CFS meet tender point criteria for fibromyalgia [15]; similarly, approximately 70 percent of patients with fibromyalgia meet the criteria for CFS [16]. (See "Clinical features and diagnosis of chronic fatigue syndrome").
Myofascial pain ? Myofascial pain is considered by many to be a localized form of fibromyalgia [17]. Patients with this disorder complain of pain in one anatomic region, such as the right side of the neck and shoulder, and tenderness is confined to that area. (See "Overview of soft tissue rheumatic disorders", section on Regional myofascial pain).
SUMMARY AND RECOMMENDATIONS ? In summary, fibromyalgia can and should be diagnosed in patients who present with chronic myalgias and arthralgias but who have no evidence of joint or muscle inflammation on physical examination or laboratory testing. The physical examination should reveal multiple tender points at specific soft tissue locations (show figure 2). Since there are no diagnostic laboratory tests, testing should be kept to a minimum.
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