Differential diagnosis of fibromyalgia

INTRODUCTION — Fibromyalgia (FM) is a common cause of chronic widespread musculoskeletal pain, often accompanied by fatigue, cognitive disturbance, psychiatric symptoms, and multiple somatic symptoms. Despite the presence of soft tissue pain affecting the muscles, ligaments, and tendons, FM itself is not associated with evidence of tissue inflammation, and a cardinal feature of FM is that the pain is not explained by another rheumatic or systemic disorder.

Explicit in the definition of FM is the exclusion of other conditions that can present with widespread pain. However, FM is often associated with other conditions that may cause musculoskeletal pain, disruption of sleep, or psychiatric symptoms; features of these conditions may also mimic FM, and the presence of such disorders should be considered in the diagnostic evaluation.

This topic will review the differential diagnosis of FM in adults. The clinical manifestations, diagnosis, and treatment of this condition in adults, as well as FM in children and adolescents, are discussed in detail elsewhere. (See "Clinical manifestations and diagnosis of fibromyalgia in adults" and "Approach to the patient with myalgia" and "Treatment of fibromyalgia in adults" and "Fibromyalgia in children and adolescents: Clinical manifestations and diagnosis" and "Fibromyalgia in children and adolescents: Treatment and prognosis overview".)

APPROACH TO THE DIFFERENTIAL DIAGNOSIS — The differential diagnosis of fibromyalgia (FM) is large, given the number of conditions that can present with signs or symptoms of FM, such as pain, fatigue and sleep disturbance, and symptoms of cognitive dysfunction and psychiatric disease [1]. However, the diagnosis of FM and the exclusion of other alternative diagnoses included in the differential diagnosis can generally can be achieved based upon a thorough history and physical examination, and requires only limited laboratory testing (table 1 and table 2). The diagnostic approach to FM is described in detail separately. (See "Clinical manifestations and diagnosis of fibromyalgia in adults", section on 'Diagnosis'.)

FM is diagnosed when characteristic features are present and other medical conditions have been excluded as the cause of the patient's symptoms. The confidence that each clinician has in making this decision is related to their level of experience, particularly in evaluating rheumatic disorders. Features of each of the major conditions in the differential and potentially confounding factors to consider in the evaluation can be identified and are summarized in the table (table 3).

There are no "objective" physical findings or specific laboratory or radiograph abnormalities that characterize FM, and there are many illnesses that present with widespread pain and fatigue; if a patient is evaluated soon after those symptoms began the differential diagnosis is vast. For example, viral syndromes, including hepatitis, should be considered, but the symptoms don't last for months. FM should only be considered after the symptoms have persisted for at least three months.

The cardinal manifestation of FM is widespread pain and that is the initial symptom that should be ascertained. Therefore, the differential diagnosis will often begin with thinking about systemic rheumatic diseases such as early rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). By contrast, some FM patients may describe fatigue or cognitive or mood disturbances as the most troublesome symptoms. In those patients, the initial differential diagnosis may be broader.

Some of the conditions in the differential diagnosis of FM, such as inflammatory musculoskeletal disorders, endocrinopathies, and neuropathies, manifest abnormal physical and/or laboratory findings that distinguish them from FM (table 3). Other conditions, which often occur as overlapping diagnoses in patients found to have FM, may be part of a spectrum sometimes termed "functional somatic syndromes" or central pain disorders, which includes FM. These disorders include: myofascial pain syndrome; chronic fatigue syndrome (CFS) also known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); irritable bowel syndrome (IBS); chronic pelvic and bladder pain disorders; and temporomandibular disorder (TMD) [2]. (See "Clinical manifestations and diagnosis of fibromyalgia in adults", section on 'Coexisting disorders'.)

ARTHRITIS AND SYSTEMIC RHEUMATIC DISEASES — Symptoms of fibromyalgia (FM) may be mistaken for those of several inflammatory and autoimmune rheumatologic disorders [3,4]. The musculoskeletal pain associated with these disorders sometimes mimics FM, but these conditions may also coexist with FM (see "Clinical manifestations and diagnosis of fibromyalgia in adults", section on 'Coexisting disorders'). These conditions include:

●Rheumatoid arthritis, Sjögren's disease, and systemic lupus erythematosus – Rheumatic diseases such as rheumatoid arthritis (RA), Sjögren's disease (SS), and systemic lupus erythematosus (SLE) may present with generalized arthralgias, myalgias, and fatigue, and like FM most often affect younger women (table 3). However, characteristic features of RA, such as multiple joint swelling, or of SLE, such as facial rash and multisystemic inflammation, do not occur in FM. A careful history and physical examination, rather than "screening" serologic blood tests, is usually sufficient to differentiate FM from a connective tissue disease, and unless there is strong clinical suspicion of a systemic rheumatic disorder, routine ordering of serologic tests is not required. (See "Diagnosis and differential diagnosis of rheumatoid arthritis" and "Diagnosis and classification of Sjögren’s disease" and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults".)

Autoantibody testing, such as antinuclear antibody (ANA) and rheumatoid factor (RF), may be positive in healthy individuals and in many other diseases, and positive tests do not exclude FM. For example, approximately 10 to 15 percent of patients with FM, like 5 to 10 percent of healthy women, have a positive ANA test [5]. Therefore, the predictive value of a positive ANA is poor in patients who have no signs or symptoms of SLE. If there is clinical confusion regarding the differential diagnosis of FM with SLE or with other systemic connective tissue diseases, more specific serologic tests, such as an anti-deoxyribonucleic acid (DNA) antibody test, may be helpful. (See "Rheumatoid factor: Biology and utility of measurement" and "Measurement and clinical significance of antinuclear antibodies".)

FM occurs more commonly in these systemic immune diseases than in the general population and can affect disease assessment. FM is present in 10 to 30 percent of patients with RA and spondyloarthritis and in an even greater number of patients with SLE and Sjögren's disease [6,7]. Early rheumatology referral is helpful when such comorbidity is likely.

●Spondyloarthritis – Ankylosing spondylitis and other inflammatory back conditions may present with axial skeletal pain and stiffness similar to that of FM and may be misdiagnosed as FM [7]. However, spinal motion in FM is generally normal, and there are characteristic imaging and radiologic features of ankylosing spondylitis and the other forms of spondyloarthritis (SpA) that are not seen in FM. Patients with SpA may have no peripheral joint abnormalities on examination. Patients presenting with poly-enthesitis may complain of widespread pain and be especially difficult to distinguish from patients with FM [8]. (See "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults".)

●Polymyalgia rheumatica – Polymyalgia rheumatica (PMR) may mimic FM, causing myalgia and stiffness in the upper and lower extremities, although this disorder can be differentiated by the history and laboratory studies. Patients with PMR tend to be older at onset and to present more with generalized stiffness than with severe, widespread pain. An elevated erythrocyte sedimentation rate (ESR) OR C-reactive protein (CRP) is present in the vast majority of patients with PMR but is normal in patients with FM. Patients with PMR, but not those with FM, respond extremely well to modest doses of glucocorticoids [9]. However, glucocorticoid withdrawal in PMR or any rheumatic condition may cause symptoms that are similar to those of FM. (See "Clinical manifestations and diagnosis of polymyalgia rheumatica".)

●Osteoarthritis – Patients with osteoarthritis (OA) have localized joint pain, restricted to affected joints, and widespread articular and periarticular pain is not present in osteoarthritis (OA). If present, coexisting FM may be considered. (See "Clinical manifestations and diagnosis of osteoarthritis".)

●Hypermobility syndromes – Nine of 11 trials in a meta-analysis found increased rates of hypermobility syndromes (including Ehlers-Danlos syndrome) among FM patients compared with controls, but analysis was limited by the poor quality of the studies [10].

A nuclear bone scan may be useful to determine whether the patient has an inflammatory arthritis versus FM, when the diagnosis cannot be established using clinical or serologic data. (See "Clinical manifestations and diagnosis of fibromyalgia in adults", section on 'Diagnosis'.)

MUSCLE DISEASE AND MYALGIA

●Inflammatory and metabolic myopathies – Fibromyalgia (FM) can be distinguished from inflammatory myositis and the metabolic myopathies by features evident on history and examination, as well as by laboratory testing, although myalgia and fatigue are prominent in both FM and disorders. of the muscles themselves. Myositis and the myopathies cause muscle weakness and muscle fatigue but are not usually associated with diffuse pain. Patients with FM do not have significant muscle weakness, other than that related to pain or disuse. In contrast to myositis, patients with FM have normal muscle enzyme tests and normal or nonspecific histopathologic findings on muscle biopsy. Muscle biopsies should not be performed unless there is clinical evidence suggestive of an inflammatory or metabolic myopathy, and routine muscle enzyme testing in patients with FM is not recommended [11]. (See "Approach to the metabolic myopathies" and "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Clinical manifestations'.)

●Statin myopathy – Symptoms of statin myopathy may occasionally mimic the musculoskeletal features of FM. At least 10 to 30 percent of subjects treated with statins experience nonspecific muscle discomfort. Those with preexisting FM are more likely to develop statin-associated muscle pain [12]. The absence of other features associated with FM, temporal association with statin therapy, and the elevation in muscle enzymes sometimes seen in patients with statin-related symptoms help to distinguish these conditions. Antibodies to HMG-CoA reductase can help establish a diagnosis of statin myopathy [13]. (See "Statin muscle-related adverse events".)

●Myalgia – A wide variety of disorders may be associated with diffuse or localized myalgia. An overview of the approach to the evaluation of patients presenting with myalgia is presented separately. (See "Approach to the patient with myalgia".)

INFECTIOUS, METABOLIC, AND NEUROLOGIC DISORDERS

●Infection – Certain viral infections, such as hepatitis or Chikungunya, are associated with arthralgias and myalgias as well as joint inflammation. FM as well as chronic fatigue syndrome (CFS), have been noted to follow or accompany well-documented infections, including human immunodeficiency virus (HIV) infection, human T-lymphotropic virus (HTLV) infection, hepatitis, and Lyme disease [14-16]. FM was the most prevalent rheumatic disorder in patients with hepatitis B or C infections [17]. Approximately 25 to 40 percent of patients with documented Lyme disease who are treated appropriately with antibiotics will develop persistent pain and fatigue, consistent with FM and CFS [15,18]. However, in one study with a decade of follow-up of 100 patients with culture-proven Lyme disease, only one subsequently developed FM during the follow-up period [19].

FM can be distinguished from chronic infection by the lack of serologic or culture evidence for ongoing infection, lack of response to antimicrobials or antiviral agents, normal acute phase reactants and complete blood count, and the presence of characteristic clinical features of FM. (See "Infectious mononucleosis" and "Diagnosis of Lyme disease" and "Musculoskeletal manifestations of Lyme disease", section on 'Post-treatment Lyme disease syndrome' and "Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome".)

Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a substantial number of patients have unexplained persistent symptoms and are diagnosed with post-acute sequelae of SARS-CoV-2 (PASC), also known as long coronavirus disease (long COVID). Fatigue is the most prominent symptom, but myalgias, cognitive disturbances, mood disturbances, and sleep disturbances are also common. Many of these patients meet diagnostic criteria for FM and/or CFS. One web-based study found that one-third of long COVID patients met the American College of Rheumatology (ACR) survey criteria for FM [20]. A mobile app screening questionnaire has been designed for application in long COVID patients who present with persistent myalgias and fatigue [21]. Many of these long COVID patients also have evidence of autonomic dysfunction and will have positive tests for postural orthostatic tachycardia syndrome (POTS) and small fiber neuropathy, both of which are common in FM and CFS. The features, evaluation, and management of these patients are described separately. (See "COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")".)

Postviral fatigue syndromes were first reported in the 1930s with brucellosis, in the 1940s and 1950s with polio, and in the 1970s with Epstein-Barr virus.  

●Endocrinopathies

•Hypothyroidism – Hypothyroidism may be difficult to distinguish from FM, since patients with hypothyroidism often complain of generalized aches, fatigue, and interrupted sleep. In patients suspected clinically of hypothyroidism thyroid function studies, such as a serum thyroid-stimulating hormone (TSH), can be used to establish the presence of thyroid disease. Thyroid function is normal in patients with FM in the absence of coexisting thyroid disease, although FM may also be a presenting manifestation of hypothyroidism, and thyroid autoantibodies are common in patients with FM [22]. However, correcting the thyroid abnormality does not usually ameliorate the FM symptoms in such patients. Routine TSH testing is not recommended [11]. (See "Diagnosis of and screening for hypothyroidism in nonpregnant adults".)

•Other endocrine disorders – Other endocrine disorders that may present with symptoms similar to FM include hyperparathyroidism and Cushing's syndrome. Hyperparathyroidism is recognized by the presence of hypercalcemia, while Cushing's syndrome presents with characteristic facial and skin features and is associated with muscle weakness rather than pain. Adrenal insufficiency causes severe exhaustion but is not typically associated with chronic, widespread pain. Some studies, but not others, have suggested that patients with vitamin D deficiency without evidence of osteomalacia may also experience symptoms of chronic musculoskeletal pain [23-25]. Two systematic reviews have found no conclusive evidence for an association of vitamin D deficiency and FM [26,27]. (See "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation" and "Epidemiology and clinical manifestations of Cushing syndrome".)

Mast cell activation syndrome, postural orthostatic tachycardia syndrome (POTS), and Ehlers-Danlos syndrome have been associated with FM-like complaints [28].

Hypophosphatasia is a genetically mediated process whose muscle pain features need to be differentiated from FM. Most patients have a low alkaline phosphatase [29].

●Neurologic disorders – Peripheral neuropathies; entrapment syndromes, such as carpal tunnel syndrome; and neurologic disorders, such as multiple sclerosis (MS) and myasthenia gravis may mimic FM [30,31]. Patients with FM may be mistakenly diagnosed with one of these neurologic diseases, since they may complain of numbness and tingling, often involving the neck; when radiating down the arm, paresthesia may suggest cervical radiculopathy. Numbness and tingling are much more prominent in FM than in RA patients [32]. MS is associated with paresthesias and MS and myasthenia are associated with post-exercise muscle fatigue, as well as generalized fatigue, both of which may be experienced by patients with FM. However, chronic, widespread pain is unusual in patients with these neurologic conditions. Patients with FM can usually be distinguished from those with peripheral or compressive neuropathy or more systemic neurologic disorders by a thorough history and physical examination, including a detailed neurologic examination.

Small fiber neuropathy has been identified in some patients with FM. The significance of this observation is still controversial [33-35]. Evidence for a small-fiber neuropathy on skin biopsy was more common in 25 FM patients compared with 55 healthy controls. This included a quantitative reduction in epidermal innervation and regeneration-sparing and myelinated nerve fibers in FM patients [35]. There has also been experimental evidence in rats that small fiber neuropathy may be related to central, rather than peripheral, nervous system mechanisms [36]. (See "Overview of polyneuropathy" and "Overview of upper extremity peripheral nerve syndromes" and "Carpal tunnel syndrome: Clinical manifestations and diagnosis" and "Evaluation and diagnosis of multiple sclerosis in adults" and "Diagnosis of myasthenia gravis".)

Orthostatic intolerance, identified by abnormal tilt table testing, and other features of dysautonomia are common in patients with FM [37]. However, most reports suggest that these symptoms are related to deconditioning and hypervigilance, rather than a primary disorder [38].

Evaluation by an expert in neurologic disease may occasionally be required to determine whether electrophysiologic testing, imaging, or other studies are necessary if the diagnosis remains uncertain, to avoid unnecessarily costly and/or invasive neurologic testing, especially in patients with only paresthesias or mild cognitive dysfunction. However, in the absence of a defined neurologic disorder, the neurologic evaluation in patients with FM sometimes reveals minor sensory and motor abnormalities, with corresponding symptoms of poor balance or coordination, tingling or weakness in the arms or legs, and numbness.

REGIONAL SOFT TISSUE PAIN

Myofascial pain syndromes

●Myofascial pain syndrome – Pain and localized soft tissue tenderness are characteristic of myofascial pain syndrome, sometimes termed repetitive strain syndrome, resembling and sometimes overlapping considerably with fibromyalgia (FM) (table 4) [39-42]. However, patients with myofascial pain syndrome typically complain of pain in one anatomic region, such as the right side of the neck and shoulder, with tenderness being confined to that area, rather than having the widespread pain typical of FM. Many of the original reports of FM actually described what would have subsequently been termed myofascial pain syndrome. (See "Overview of soft tissue musculoskeletal disorders", section on 'Myofascial pain syndrome'.)

Some of the confusion lies in the differentiation between the trigger points of myofascial pain and the tender points present in FM. Myofascial pain is defined by the presence of trigger points that are found in a taut band in the muscle (figure 1). A characteristic referral pain pattern is activated when pressure is applied to a trigger point [39-41]. Some experts also insist upon the presence of a local twitch response, a visible or palpable contraction of the muscle produced by a rapid snap of the examining finger to the taut band of muscle. By contrast, tender points, as seen in FM, are soft tissue sites that are excessively tender on manual palpation. However, the reliability of the trigger point examination has been questioned [41,42]. Some authors have concluded that FM and myofascial pain are "two sides of the same coin" [43].

●Other regional pain disorders – Other common regional pain disorders overlap with FM; these include tension headaches, idiopathic low back and cervical strain disorders, repetitive strain syndromes, occupational overuse syndrome, cumulative trauma disorder, work-related musculoskeletal disorder, and temporomandibular disorder (TMD) [2,41,42].

In the head and neck, the pain may be associated with unexplained dizziness and with neurocognitive disturbances. Some neurovestibular abnormalities may be found in patients with TMD and myofascial pain of the head, and TMD may also share other features with FM. These poorly understood pain disorders are also associated with fatigue, sleep abnormalities, and psychiatric symptoms, suggesting that myofascial pain disorders may represent localized or regional forms of FM. Several of these conditions, including chronic headache, TMD, and chronic pelvic pain are now considered part of the spectrum of central pain disorders or functional somatic syndromes. (See 'Functional somatic syndromes' below and "Tension-type headache in adults: Etiology, clinical features, and diagnosis" and "Evaluation of low back pain in adults" and "Evaluation of the adult patient with neck pain" and "Overview of overuse (persistent) tendinopathy" and "Temporomandibular disorders in adults" and "Chronic pelvic pain in adult females: Evaluation".)

●Complex regional pain syndrome – Complex regional pain syndrome is usually considered to involve one extremity and is typically precipitated by trauma and immobility of that extremity. However, 10 to 20 percent of patients develop widespread pain and will meet criteria for FM [44]. There is evidence of central sensitization in complex regional pain syndrome similar to that which characterizes FM [45]. (See "Complex regional pain syndrome in adults: Pathogenesis, clinical manifestations, and diagnosis" and "Complex regional pain syndrome in adults: Treatment, prognosis, and prevention".)

Most patients have normal acute phase reactants, but a diagnosis can be established using a triple-phase bone scan of the extremities [46]. (See "Complex regional pain syndrome in adults: Pathogenesis, clinical manifestations, and diagnosis", section on 'Bone scintigraphy'.)

Tendinitis and bursitis — Patients with FM may be mistakenly diagnosed with a localized tendinopathy or bursitis based upon localized periarticular tenderness in the absence of a systemic or local arthritis. The presence of other features in the medical history characteristic of FM and a more generalized musculoskeletal examination that is not confined to a single most painful region can reveal other symptoms and more widespread tender points typical of FM and help to distinguish these conditions. (See "Overview of soft tissue musculoskeletal disorders".)

OTHER DISORDERS THAT MAY OVERLAP WITH FM — In addition to arthritis and other musculoskeletal disorders, a number of conditions with some features resembling FM may either coexist with fibromyalgia (FM) or occur independently, and some of these disorders are considered part of a FM spectrum. These include myofascial pain disorders (see 'Regional soft tissue pain' above); functional somatic syndromes, including irritable bowel syndrome (IBS), migraine, and chronic fatigue syndrome (CFS) (table 5); and psychiatric and sleep disorders [42,47-50]. (See "Clinical manifestations and diagnosis of fibromyalgia in adults" and 'Functional somatic syndromes' below and 'Chronic fatigue syndrome' below and 'Psychiatric disorders' below and 'Sleep disturbance' below.)

Functional somatic syndromes — FM is often present in patients together with other common functional somatic syndromes, including CFS, IBS, migraine, and temporomandibular joint (TMJ) disorder, as well as chronic bladder and pelvic pain syndromes [42,47-50]. Most of these conditions can be readily distinguished clinically from FM by the localized nature of the pain (for example, chronic, widespread pain in FM, abdominal pain in IBS, and jaw pain in temporomandibular disorder). The relationship of these disorders to FM is described separately. Psychogenic rheumatism is seen primarily in males with severe emotional distress who complain of chronic, widespread pain in nonanatomic distributions (eg, pain on the left side of the body from the head to the toe) [51]. (See "Clinical manifestations and diagnosis of fibromyalgia in adults", section on 'Coexisting disorders'.)

Chronic fatigue syndrome — Demographic, clinical, and potential pathophysiologic characteristics of CFS and other functional somatic syndromes are very similar to those of FM; these patients often have fatigue, cognitive disturbances, and generalized allodynia and hyperalgesia (table 5) [2,47]. Like FM and other functional somatic syndromes, CFS is diagnosed when other diseases have been excluded using a set of diagnostic criteria established for research purposes, and the diagnosis tends to be controversial because of the absence of a specific diagnostic test. These conditions may be considered as part of the same spectrum, and many patients with FM meet diagnostic criteria for CFS and vice versa [52]. However, CFS criteria do not include the presence of chronic widespread musculoskeletal pain. Both CFS and FM have been associated with autonomic nervous system abnormalities, including postural orthostatic tachycardia syndrome (POTS) and small fiber neuropathy. (See "Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome" and "Clinical manifestations and diagnosis of fibromyalgia in adults".)

Psychiatric disorders — Psychiatric disorders, including depression, anxiety disorders, and posttraumatic stress disorder (PTSD), share a number of features with FM. In addition, they are also more frequent in FM than in other rheumatic diseases (see "Clinical manifestations and diagnosis of fibromyalgia in adults", section on 'Coexisting disorders'). Depression is characterized by low mood, reduced energy, sleep and cognitive disturbances, and often by somatic features. Anxiety and PTSD are often associated with depression and sleep disturbances, resulting in fatigue, and patients with anxiety may have somatic features as well. (See "Unipolar depression in adults: Assessment and diagnosis" and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical features, assessment, and diagnosis".)

In contrast to patients with FM alone, depression is associated with persistent depressed mood, loss of interest or pleasure in most activities, thoughts of worthlessness, and recurrent thoughts of death or suicidal ideation; anxiety is associated with excessive and persistent worrying; and PTSD is associated with marked responses, such as flashbacks, severe anxiety, and fleeing or combative behavior, in response to stimuli reminding the patient of trauma they experienced, along with avoidance, emotional numbing, and diminished interest in people and activities. The distinction between FM and these conditions can usually be established by a thorough history and physical examination, but attribution of symptoms in patients with both FM and a psychiatric disorder specifically to one or the other of these causes may not always be possible.

Sleep disturbance — Most patients with FM have nonrestorative sleep and fatigue as features of their illness, symptoms that also occur in primary sleep disorders, such as obstructive sleep apnea, restless legs syndrome, and periodic limb movement disorders (PLMD). However, these primary sleep disorders are also common in patients with FM. (See "Clinical manifestations and diagnosis of fibromyalgia in adults", section on 'Coexisting disorders'.)

In contrast to patients with FM, the primary sleep disorders are generally not associated with chronic widespread pain. Obstructive sleep apnea is characterized by obstructive apneas and hypopneas, often with loud snoring, gasping, or snorting during sleep. Restless leg syndrome is typified by voluntary leg movements prompted by an urge to move, and is maximal at rest, worse at night and relieved by movement. PLMD is characterized by involuntary movements during sleep, mainly of the legs, which may or may not be symptomatic. A detailed sleep history can help identify the primary sleep disorders, although a firm diagnosis of some of these conditions, such as sleep apnea or PLMD requires formal testing in a sleep clinic. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults" and "Clinical features and diagnosis of restless legs syndrome and periodic limb movement disorder in adults".)

FATIGUE — The differential diagnosis of fatigue, a major symptom of fibromyalgia (FM), is quite broad. Medical or psychiatric diagnoses can explain fatigue in approximately two-thirds of patients with complaints of chronic fatigue, but in some patients fatigue is idiopathic, and less often may be attributed to chronic fatigue syndrome (CFS). The differential diagnosis of fatigue and a discussion of CFS are presented in detail separately. (See "Approach to the adult patient with fatigue" and "Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Fibromyalgia (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Limited role of testing to establish diagnosis – A careful history and physical examination, rather than serologic testing, should be sufficient to differentiate fibromyalgia (FM) from most rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's disease (table 1 and table 3). Selected laboratory or imaging findings, in addition to the history and physical examination, may be useful in distinguishing FM from ankylosing spondylitis, polymyalgia rheumatica (PMR), inflammatory or metabolic myopathies, chronic infection, hypothyroidism, and other endocrine disorders in patients in whom one of these conditions is suspected clinically. Routine autoimmune serologic testing or creatine kinase or thyroid-stimulating hormone (TSH) are not useful. FM can co-occur with some rheumatic diseases, which can complicate its diagnosis. (See 'Arthritis and systemic rheumatic diseases' above and 'Muscle disease and myalgia' above and 'Infectious, metabolic, and neurologic disorders' above.)

The approach to diagnosis of FM is discussed in detail elsewhere. (See "Clinical manifestations and diagnosis of fibromyalgia in adults", section on 'Diagnostic evaluation'.)

●Neurologic mimics of fibromyalgia – Peripheral neuropathies, entrapment syndromes (such as carpal tunnel syndrome), and neurologic disorders (such as multiple sclerosis [MS] and myasthenia gravis) may mimic FM. A subset of FM patients meet preliminary diagnostic criteria for small fiber neuropathy, although the clinical significance of this finding is controversial. MS and myasthenia gravis are associated with post-exercise muscle fatigue, as well as generalized fatigue. However, chronic, widespread pain is unusual. The neurologic examination should differentiate FM from most neurologic disease. Unless there is evidence of associated nerve compression or of cervical or lumbar spinal stenosis, extensive testing, including imaging and electrophysiologic testing, is not generally necessary. (See 'Infectious, metabolic, and neurologic disorders' above.)

●Pain conditions – Myofascial pain syndrome and other regional pain conditions (eg, complex regional pain syndrome) overlap considerably with FM (table 4). Patients with myofascial pain syndrome complain of pain in one anatomic region, with tenderness being confined to that area. Some of the confusion lies in the differentiation between trigger points and tender points. Myofascial pain is defined by the presence of trigger points that are found in a taut band in the muscle (figure 1). A characteristic referral pain pattern is activated when pressure is applied to a trigger point. (See 'Regional soft tissue pain' above.)

●Functional syndromes – FM is often present in patients together with other common functional somatic syndromes, including chronic fatigue syndrome (CFS) (table 5), irritable bowel syndrome (IBS), migraine, and temporomandibular dysfunction, as well as chronic bladder and pelvic pain syndromes. These conditions are sometimes considered as being part of a common disease spectrum with FM. Demographic, clinical, and potential pathophysiologic characteristics of CFS, IBS, and other functional somatic syndromes are very similar to those of FM. Except for CFS, complaints in these conditions are usually localized, unlike FM. (See 'Functional somatic syndromes' above and 'Chronic fatigue syndrome' above.)

●Psychiatric disorders – Psychiatric disorders are common in FM and have symptoms that can mimic FM. Depression is characterized by low mood, reduced energy, sleep and cognitive disturbances, and often by somatic features. Anxiety and posttraumatic stress disorder (PTSD) are often associated with depression and sleep disturbances, resulting in fatigue, and patients with anxiety may have somatic features as well. However, each of these disorders has characteristic features not found in patients with FM alone that help to distinguish these conditions from FM. (See 'Psychiatric disorders' above.)

●Sleep disturbance – Sleep disturbances are common in patients with FM, including primary sleep disturbances, such as sleep apnea, restless leg syndrome, and repetitive leg movement disorders. These conditions have symptoms that can mimic FM, including nonrestorative sleep and fatigue. A careful sleep history can help to distinguish these conditions from FM, but the definite diagnosis of sleep apnea and periodic limb movement disorder requires formal sleep testing. (See 'Sleep disturbance' above.)