Fibromyalgia in children and adolescents: Clinical manifestations and diagnosis

INTRODUCTION — 

Fibromyalgia is characterized by chronic, diffuse musculoskeletal pain and may include a range of other symptoms and comorbid conditions, such as fatigue, nonrestorative sleep, chronic headaches, and mood disturbances or disorders. While the exact etiology and pathogenesis of this disorder are unknown, fibromyalgia is thought to be largely driven by nociplastic pain related to central pain sensitization [1-3]. In some pediatric rheumatology clinics, these disorders are referred to as "amplified musculoskeletal pain syndromes" [4].

This topic reviews the clinical manifestations and diagnosis of fibromyalgia in children and adolescents. The treatment and prognosis of juvenile primary fibromyalgia syndrome (JPFS) are presented separately. (See "Fibromyalgia in children and adolescents: Treatment and prognosis overview".)

Fibromyalgia in adults has some distinct differences from JPFS [5] and is discussed in detail separately. (See "Fibromyalgia: Clinical manifestations and diagnosis in adults" and "Fibromyalgia: Treatment in adults".)

TERMINOLOGY — 

In medical literature, fibromyalgia in children is often called "juvenile primary fibromyalgia syndrome" (JPFS) or "juvenile-onset fibromyalgia" [4,6]. When working with patients and families, providers may prefer to use the term "central sensitization" instead of JPFS in order to better highlight the underlying defect in pain processing and to avoid the stigma that is often attached to fibromyalgia [7]. In this topic, we will use the term JPFS to refer to fibromyalgia in children and adolescents, given its greater specificity and widespread use in the literature.

EPIDEMIOLOGY — 

The worldwide prevalence of juvenile primary fibromyalgia syndrome (JPFS) is estimated to be approximately 1 to 6 percent in school-aged children and adolescents [8-11], although it is difficult to ascertain reliable estimates due to diagnostic variability. In studies, patients with fibromyalgia account for around 7 to 15 percent of all cases referred to tertiary pediatric rheumatology centers [8,12,13]; in the authors' experience, it is often higher.

The age of onset of JPFS is typically in the early to middle adolescent years. In a cohort study of 201 patients with JPFS who enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, the ages at baseline visit ranged from 9 to 20 years (mean 15.4±2.2 years) [14]. JPFS is virtually nonexistent in children under four years of age and is thought to be rare in children under nine years of age, although some researchers have argued that JPFS may be underrecognized in this group [15].

There is a strong female predominance for JPFS, similar to that seen for fibromyalgia in adults [11,14,15]. In the same CARRA cohort described above, 84 percent of patients with JPFS were female [14]. Multiple retrospective studies also noted that most patients with JPFS identify as non-Hispanic and White [11,14,15]. However, it is unclear how unmeasured factors may explain or mediate the observed relationship between JPFS, race, and ethnicity [14], especially since it is well documented that other types of pain are underrecognized and undertreated among patients identifying with certain racial and ethnic groups [16].

ETIOLOGY — 

Fibromyalgia is defined as a nociplastic pain syndrome. Nociplastic pain is caused by altered nociceptive function in the absence of active inflammation and/or tissue or nervous system damage and may be related to increased sensitivity in the peripheral and/or central nervous system [1]. It is distinct from nociceptive and neuropathic pain, which are related to inflammation or damage in tissues or the nervous system, respectively (table 1).

Nociplastic pain syndromes like fibromyalgia are characterized by central pain sensitization [1], where nociceptive neurons in the central nervous system become more responsive to normal or lower-than-normal afferent input [17]. Many researchers have proposed that central sensitization is caused by neuroendocrinologic changes in the central and peripheral nervous systems that occur in genetically susceptible persons, possibly in response to environmental triggers (eg, acute illness, emotional or physical trauma). The subsequent disordered pain regulation leads to an increase in nociplastic pain with hypersensitivity to various stimuli and a heightened perception of pain.

Patients with certain conditions that increase nociceptive and/or neuropathic pain may be at higher risk for developing central pain sensitization and subsequent fibromyalgia. As an example, there is a strong association between joint hypermobility and central pain sensitization [18,19]. In addition, patients with chronic nociceptive pain due to a rheumatic disease (eg, juvenile idiopathic arthritis [JIA]) may develop comorbid fibromyalgia [20]. (See 'Other overlapping and comorbid conditions' below.)

More information on factors that may be involved in the etiology and pathogenesis of fibromyalgia, including genetic changes, altered pain processing, central and autonomic nervous system dysfunction, and small fiber polyneuropathy, is provided elsewhere. (See "Pathogenesis of fibromyalgia".)

CLINICAL PRESENTATION

Common symptoms and comorbidities — By definition, patients with juvenile primary fibromyalgia syndrome (JPFS) have chronic, widespread pain. They may also experience a variety of other symptoms such as fatigue, headache, and mood or sleep disturbances, which in some cases indicate the presence of an overlapping comorbid condition, as outlined in the table (table 2).

Diffuse, widespread pain — The cardinal manifestation of JPFS is diffuse musculoskeletal pain, which typically has the following characteristics:

●Location – Patients often describe diffuse pain in the joints, muscles, and other soft tissues of the arms, legs, back, and neck. While pain may not affect all of these areas simultaneously, it is important to recognize that JPFS is not a localized phenomenon. Affected patients frequently say, "I hurt all over" or "Everything hurts."

●Quality – The quality of pain is variable. It is often described as aching; it may also be dull, sharp, shooting, or burning.

●Intensity – Pain is most often rated as moderate to severe in intensity by individuals evaluated in rheumatology clinic [14] and may be described by some patients as "excruciating." Symptoms of both allodynia and hyperalgesia are common.

●Temporal pattern – Pain is usually constant rather than intermittent and does not vary predictably throughout the day or night. While sleep disturbances are common in patients with JPFS, the pain rarely wakes patients up from sleep; the presence of nocturnal awakenings due to pain should prompt consideration of alternative diagnoses. (See 'Differential diagnosis' below.)

●Duration – Chronicity of symptoms is a required element of the classification and diagnostic criteria for JPFS and fibromyalgia in adults, with the American College of Rheumatology (ACR) specifying a minimum duration of three months (table 3) [21,22]. (See 'Classification and diagnostic criteria' below.)

●Aggravating and alleviating factors – Pain may be exacerbated by exercise, anxiety, physical or mental stress, or changes in the weather [14]. It is not usually relieved by nonsteroidal antiinflammatory drugs (NSAIDs) [23].

●Associated symptoms in painful areas – Patients may note joint stiffness or subjective soft tissue swelling in their extremities, which is reported by over 20 percent of patients with JPFS [14]. Around a third of patients also report numbness or tingling in their affected extremities [14].

When pain is concentrated in or around joints, providers should assess carefully for alternative causes of pain, such as inflammatory arthritis or enthesitis. Similarly, while patients may experience muscle pain and fatigue, they should not have objective weakness, as can be seen in various types of myopathies. (See 'Differential diagnosis' below.)

Headache — Frequent headaches occur in a majority of patients with JPFS, with a reported prevalence of 55 to 80 percent [14,24-27]. While data describing the type of headache in JPFS are limited, adults with fibromyalgia most commonly experience tension-type or migraine headaches [28-30].

Children and adolescents with frequent headaches may benefit from evaluation for a comorbid headache disorder, which is described in detail separately. (See "Headache in children: Approach to evaluation and general management strategies".)

Fatigue — Fatigue is a common complaint in children with fibromyalgia, similar to adults with this disorder. Most retrospective studies of patients with JPFS have reported a high prevalence of fatigue (80 to 100 percent) [14,24,31], although one series noted a lower prevalence (20 percent) [32]. While the specific types of fatigue are not well described in JPFS, patients may experience excessive sleepiness and physical, mental, and/or emotional exhaustion [33]. In one cohort of patients with JPFS, 14 percent reported hypersomnia [14]. Fatigue in JPFS likely stems from multiple aspects of the disease, including deconditioning from functional changes related to pain, as well as comorbid sleep and mood disturbances.

It can be difficult to distinguish when patients with JPFS have prominent fatigue or have a comorbid syndrome characterized by fatigue, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or "long COVID" [34,35]. Researchers have documented many similarities in the symptoms of adults with fibromyalgia and ME/CFS [36,37], although diffuse pain is not a hallmark of ME/CFS or long COVID. The clinical manifestations and diagnosis of ME/CFS and long COVID are presented separately. (See "Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome" and "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")".)

Sleep disturbance — At least two-thirds of patients with JPFS experience disturbed or interrupted sleep [12,26,38-42], which may include the following components:

●Increased sleep latency – Increased sleep latency is reported by more than 40 percent of patients with JPFS [14]. It may take an hour or more to fall asleep despite severe fatigue.

●Nighttime awakenings – Around 40 percent of patients with JPFS also struggle with frequent nighttime awakenings [14]. While patients who wake up often note that pain is still present, pain itself should not be causing nighttime awakenings.

●Nonrestorative sleep – Nonrestorative sleep (feeling tired or exhausted even after getting a full night's sleep) affects over half of children with JPFS [14].

Patients may also have comorbid conditions that affect their sleep quality. As an example, periodic limb movement disorder (PLMD) may be underrecognized in patients with JPFS [26]. The clinical manifestations and evaluation of sleep disorders in children, including PLMD, are discussed in detail separately. (See "Assessment of sleep disorders in children" and "Restless legs syndrome and periodic limb movement disorder in children".)

Mood disturbance — JPFS has been associated with multiple types of mood disturbances as well as mental health and behavioral disorders, including depression and anxiety [24,43,44]. Children with JPFS are also more likely to have temperamental instability and increased vulnerability to stress compared with healthy children or children with inflammatory arthritis [25]. It is unclear whether there is a causal relationship between JPFS and any of these conditions and, if so, whether JPFS is a cause or an effect [39,45]. Theoretically, there may be some shared underlying pathophysiology if JPFS is related to neuroendocrine changes in the central and peripheral nervous systems, which could presumably also impact mental health. (See 'Etiology' above.)

Regardless of causality, the presence of a comorbid mental health disorder can negatively impact the symptoms and outcomes of JPFS, and vice versa. As examples, the long-term prognosis of patients with JPFS may be worse among those with more depressive symptoms [46], while depressive symptoms might be exacerbated by the experience and consequences of being in chronic pain.

The clinical manifestations and diagnosis of depression and anxiety disorders in children are described in detail separately. (See "Pediatric unipolar depression: Epidemiology, clinical features, assessment, and diagnosis" and "Anxiety disorders in children and adolescents: Assessment and diagnosis".)

Other overlapping and comorbid conditions — JPFS may co-occur with a number of other conditions that may share some underlying pathophysiology [47] and which are described in detail elsewhere, including the following:

●Pediatric hypermobility syndromes [48] (see "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder", section on 'Pediatric hypermobility syndromes')

●Temporomandibular joint disorder [49,50] (see "Temporomandibular disorders in adults")

●Autonomic dysfunction including orthostatic hypotension and postural orthostatic tachycardia syndrome [51,52] (see "Mechanisms, causes, and evaluation of orthostatic hypotension" and "Postural tachycardia syndrome")

●Gastrointestinal disorders such as irritable bowel syndrome (see "Chronic abdominal pain in children and adolescents: Approach to the evaluation")

●Disorders causing pelvic pain such as interstitial cystitis/bladder pain syndrome, endometriosis, and vulvodynia [53,54] (see "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis" and "Endometriosis in adults: Clinical features, evaluation, and diagnosis" and "Vulvar pain of unknown cause (vulvodynia): Clinical manifestations and diagnosis")

There may also be a relationship between fibromyalgia and other chronic autoimmune conditions including celiac disease, psoriasis, type 1 diabetes, and thyroid disorders [55-60].

Finally, patients with systemic rheumatic diseases (eg, juvenile idiopathic arthritis [JIA]) may develop comorbid JPFS [20,61,62], possibly related to central pain sensitization from chronic nociceptive pain. The diagnosis and management of fibromyalgia in patients with chronic rheumatic diseases is described in detail separately. (See "Overview of chronic widespread (centralized) pain in the rheumatic diseases".)

Psychosocial impact — Children may suffer from JPFS for months to even years before being diagnosed, leading to significant disruptions in their day-to-day life. As an example, patients with JPFS commonly struggle to attend school regularly due to their symptoms and may switch to home schooling. In one cohort study of adolescent patients with JPFS, patients missed an average of three days of school per month [63]. In addition, patients tend to reduce or stop their participation in physical activity and team sports, which can lead to deconditioning, poorer quality of sleep, and worsening symptoms of fibromyalgia.

Physical findings — The physical examination for patients with JPFS is most notable for the absence of findings that suggest alternative diagnoses (eg, arthritis, enthesitis, myopathy). Positive findings may include the following:

●Tender points – Tender points are highly localized areas of the body that are consistently sensitive to pressure among patients with JPFS (figure 1) [21,22]. Palpation of these areas may be painful and elicit a pain response, such as wincing or withdrawal; however, tender points are not universal, nor are they required for diagnosis [64]. Prior to examination, patients are usually not aware that these areas are especially sensitive; however, anticipation of pain with palpation may affect results, contributing to challenges of the tender point examination. Children with JPFS often have multiple tender points on examination [24].

●Allodynia or hyperalgesia – Patients may exhibit hyperalgesia, where there is an increased pain response to painful stimuli (eg, pain with firm palpation of joints), and/or allodynia, where there is pain to a nonpainful stimulus (eg, light touch).

●Joint hypermobility – Joint hypermobility is noted in over a quarter of patients with JPFS [14]. While the exact relationship between joint hypermobility and JPFS is unclear, it may be that recurrent microtrauma to joints contributes to central pain sensitization [48]. The frequent occurrence of joint hypermobility has been cited as one difference between the manifestations of fibromyalgia in children and adults [5]; however, this observation may be related to the general decrease in joint mobility with increasing age.

●Deconditioning – Patients who have had longstanding symptoms that interfered with their ability to participate in regular activities and exercise may show signs of deconditioning, such as muscle atrophy. In such instances, it is especially important to exclude alternative diagnoses (eg, myopathy, neuropathy).

Laboratory and imaging findings — All laboratory and imaging tests should be normal in patients with primary JPFS. An exception is when patients have an underlying chronic rheumatic or other autoimmune/autoinflammatory disease in addition to JPFS; however, in these cases, it is important to not ascribe pain to JPFS alone, particularly if there is any evidence of ongoing rheumatic disease activity (eg, elevated inflammatory markers).

EVALUATION AND DIAGNOSIS

When to suspect fibromyalgia — Juvenile primary fibromyalgia syndrome (JPFS) should be suspected in older children (typically >9 years old) who have chronic (typically >3 months), diffuse, widespread pain that impacts their daily activities and is associated with other symptoms such as headache, fatigue, sleep or mood disturbances, abdominal pain, irritable bowel symptoms, and/or orthostatic hypotension.

History — The history in children suspected of having JPFS is focused on excluding alternative diagnoses as well as assessing the extent of symptoms and the subsequent psychosocial impact.

When obtaining the history, we typically ask patients and their caregivers about the following elements:

●The onset of symptoms, including if there were any potential predisposing factors or triggers such as infections, vaccinations, physical injuries, or physically or psychologically stressful events.

●The type of pain, including its location, quality, intensity, temporal pattern, duration, and aggravating factors (eg, physical activity, stress, changes in the weather).

●Other symptoms in addition to pain, including headache, fatigue, sleep or mood disturbances, abdominal pain, irritable bowel symptoms, and/or orthostatic hypotension.

●The impact of symptoms on their daily activities, including school attendance and physical activity, and any positive coping strategies they have identified.

●The use of any specific treatments and the outcome, including nonsteroidal antiinflammatory drugs (NSAIDs), topical medications (eg, diclofenac gel), dietary changes, supplements, physical therapy, and/or complementary and alternative medicine practices (eg, acupuncture, massage).

●A family history of fibromyalgia or related conditions (eg, headache disorders, irritable bowel syndrome, joint hypermobility), as well as autoimmune or autoinflammatory conditions (eg, autoimmune thyroid disease, inflammatory arthritis, psoriasis, inflammatory bowel disease).

●Whether the patient or caregivers have any specific ideas or concerns about what might be causing the symptoms, since developing a shared understanding of the origin of symptoms will be important for subsequent management of possible JPFS.

Standardized measures can be used to assess the impact of JPFS on function and quality of life [65,66], although these are primarily designed for research purposes.

Physical examination — The physical examination should be comprehensive, with particular attention to the following areas:

●Growth – We review the patient's growth chart for any significant deviations in their expected trajectories for height or weight. When present, changes may be related to JPFS (eg, weight gain due to decreased physical activity) or suggest an alternative diagnosis (eg, thyroid dysfunction, celiac disease). Further workup is indicated, as described elsewhere. (See "Poor weight gain in children younger than two years in resource-abundant settings: Etiology and evaluation" and "Clinical evaluation of the child or adolescent with obesity".)

●Musculoskeletal examination – When examining the joints, providers should look for any evidence of inflammation in joints and entheses (ie, where tendons attach to bones), such as focal tenderness, pain with movement, warmth, redness, swelling, or limited joint mobility. We assess for joint hypermobility, typically by using the Beighton Scoring System as illustrated in the figure (figure 2). More detailed information on how to perform a musculoskeletal examination in a child with joint pain is provided separately. (See "Evaluation of the child with joint pain and/or swelling", section on 'Focused joint examination'.)

We also check for focal pain at tender points as shown in the figure (figure 1). The presence of tender points is clinically useful in making the diagnosis of JPFS or fibromyalgia; however, it is not necessary, as reflected by the revised American College of Rheumatology (ACR) classification system for adult fibromyalgia [22]. Having tender points is also insufficient in isolation to make a diagnosis of fibromyalgia, and in the absence of chronic pain it does not appear to be predictive of later development of JPFS [67]. (See 'Physical findings' above and 'Classification and diagnostic criteria' below.)

●Neurologic examination – We look for any evidence of muscle atrophy or objective weakness, which may be a sign of underlying myopathy. In addition, we observe for any nonreflexive pain behaviors (ie, posturing or guarding that would be expected to increase, rather than decrease pain), as these may suggest that most neural activity is beyond the junctions at the dorsal horn of the spinal cord (ie, the site of pain reflexes) due to central sensitization.

Diagnostic testing — There are no specific laboratory or imaging tests that are diagnostic of fibromyalgia. Thus, in the absence of signs or symptoms that suggest an alternative diagnosis, we send a limited set of laboratory tests for most patients suspected of having JPFS that includes the following:

●Complete blood count (CBC)

●Acute phase reactants (ie, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP])

●Basic metabolic panel

●Thyroid-stimulating hormone (TSH)

We do not routinely test for rheumatoid factor (RF) or antinuclear antibodies (ANA) due to the nonspecific nature of such testing and the concern caused by false-positive values. However, we do send these tests if there are specific symptoms or examination findings that are concerning for inflammatory arthritis or ANA-related systemic autoimmune diseases (eg, systemic lupus erythematosus [SLE]). (See "Measurement and clinical significance of antinuclear antibodies", section on 'Clinical utility and limitations of ANA testing'.)

Imaging of painful areas is rarely indicated unless there is a history of prior injuries or concern for an alternative diagnosis.

Similarly, we do not routinely obtain sleep studies or polysomnography for patients suspected of having JPFS who have fatigue or sleep disturbances unless there are symptoms to suggest a primary sleep disorder (eg, obstructive sleep apnea, restless legs syndrome). The clinical manifestations and evaluation of sleep disorders in children are discussed in detail separately. (See "Assessment of sleep disorders in children" and "Restless legs syndrome and periodic limb movement disorder in children".)

Features suggesting an alternative diagnosis — Features that should alert the provider that an alternative diagnosis is likely include the following:

●Young age, especially <4 years old

●Focal pain awakening the patient at night

●Evidence of systemic inflammation based on symptoms (eg, fever) or laboratory testing (eg, elevated ESR or CRP)

●Signs or symptoms of arthritis or enthesitis (eg, focal joint swelling, redness, warmth, contractures)

●Focal weakness

More information on the differential diagnosis of JPFS is provided below. (See 'Differential diagnosis' below.)

Establishing the diagnosis — The diagnosis of JPFS is made clinically and is based upon a history of chronic, generalized pain and associated features (eg, fatigue, sleep disturbances, headache, and mood disturbances); a physical examination that may demonstrate the presence of tender points and also excludes alternative diagnoses; and negative or normal laboratory testing. In our practice and in those of many pediatric rheumatologists, we use the Yunus and Masi diagnostic criteria (table 3) as part of our clinical evaluation [24]. (See 'Classification and diagnostic criteria' below and 'Clinical presentation' above.)

WHEN TO REFER — 

Patients who are suspected of having juvenile primary fibromyalgia syndrome (JPFS) can be diagnosed on the basis of the aforementioned criteria. If there is diagnostic uncertainty, cases can be referred to a pediatric rheumatologist for evaluation and, depending on local practice patterns, to a pediatric rheumatologist or a pediatric pain specialist for management. Patients who are diagnosed with JPFS may benefit from additional referrals (eg, to pain medicine and physical therapy), which are discussed separately. (See "Fibromyalgia in children and adolescents: Treatment and prognosis overview".)

DIFFERENTIAL DIAGNOSIS — 

There are a variety of conditions that may cause chronic, diffuse pain and other symptoms seen in juvenile primary fibromyalgia syndrome (JPFS). While the level of suspicion for these alternative diagnoses may vary slightly depending on the patient's most prominent associated symptoms (eg, joint pain, fatigue), general considerations include the following:

●Complex regional pain syndrome (CRPS) type 1 – Moderate to severe pain that is localized to an extremity should prompt consideration of complex regional pain syndrome type 1. The diagnostic criteria for CRPS (according to the Budapest criteria) include ongoing pain that is disproportionate to an inciting event, hyperalgesia and allodynia (severe pain with even light stroking of the skin of the affected area), and edema, sweating, and changes in color or temperature in the affected limb [68]. The extent of these changes varies from subtle to extreme, with severe atrophy and trophic changes of the skin, hair, and nails and significant dysfunction of involved muscles and joints. (See "Complex regional pain syndrome in children".)

CRPS and JPFS can be distinguished by the extent of pain, which is localized in CRPS versus diffuse and widespread in JPFS. In addition, while children with CRPS may have other symptoms that are seen in JPFS (eg, sleep disturbances, psychologic stress), the fatigue and headaches are less prominent and autonomic dysfunction is typically localized to the affected limb.

●Growing pains – Growing pains can cause recurrent episodes of limb pain, typically in the bilateral lower extremities and often correlated with activity. They most commonly occur in the late afternoon or night and may wake the patient up from sleep. Most patients with growing pains are between ages 3 and 12 years old; teenagers are rarely affected. (See "Growing pains".)

A key difference between growing pains and JPFS is the location and pattern of pain, which is localized and intermittent in patients with growing pains, versus diffuse and constant in those with JPFS. Growing pains are typically relieved by nonsteroidal antiinflammatory drugs (NSAIDs), while pain in JPFS often is not. In addition, children with growing pains do not have the other associated symptoms seen in JPFS. Finally, while the age ranges of patients with growing pains and JPFS overlap, growing pains typically affect younger children, while JPFS affects older children and adolescents.

●Thyroid dysfunction – Patients with hypothyroidism may develop fatigue and arthralgia, while those with hyperthyroidism may develop myopathy characterized by myalgia and muscle weakness. Thyroid dysfunction can be distinguished from JPFS through thyroid hormone testing, which is routinely done as part of the evaluation for patients suspected of having JPFS. (See 'Diagnostic testing' above and "Acquired hypothyroidism in childhood and adolescence" and "Myopathies of systemic disease", section on 'Hyperthyroid myopathy'.)

●Rheumatic diseases – A variety of rheumatic diseases may cause diffuse musculoskeletal pain, including the following:

•Juvenile idiopathic arthritis – Patients with juvenile idiopathic arthritis (JIA) may present with widespread pain of their affected joints. Certain types of JIA may also cause enthesitis, or inflammation at the insertion of the tendons onto bones. (See "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications" and "Oligoarticular juvenile idiopathic arthritis" and "Spondyloarthritis in children".)

JIA and JPFS can typically be distinguished based on a combination of clinical features, physical examination findings, and diagnostic studies. Patients with JIA often experience prolonged morning joint pain and stiffness (ie, >2 hours) which gradually improves with activity and/or NSAIDS; by contrast, patients with JPFS typically have worse pain with activity and less benefit from NSAIDs. Back pain is common in JPFS, while back pain related to axial arthritis is only seen in certain types of JIA (eg, enthesitis-related arthritis, psoriatic JIA). On examination, patients with both JIA and JPFS may have tender joints or pain with range of motion. However, those with JIA should have objective signs of synovitis such as swelling, warmth, erythema, and/or limited range of motion, while those with JPFS will have pain in nonarticular areas (eg, muscles, soft tissues). Patients with JIA may have asymmetric sites of pain, whereas JPFS patients report symmetric and widespread pain. On laboratory evaluation, inflammatory markers (ie, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) may be elevated in JIA and should be normal in JPFS.

•Systemic autoimmune diseases – Children with systemic autoimmune diseases, such as childhood-onset systemic lupus erythematosus (cSLE) or juvenile dermatomyositis (JDM), may develop pain related to inflammation in joints and/or muscles. Patients may have systemic symptoms, such as fatigue, fever, and weight loss. Other types of disease manifestations vary; as examples, patients with cSLE may have mucocutaneous manifestations (eg, rash, oral ulcers), serositis (eg, pericarditis), and/or nephritis, while patients with JDM can develop objective muscle weakness, a heliotrope rash, and Gottron's papules. (See "Childhood-onset systemic lupus erythematosus (cSLE): Clinical manifestations and diagnosis" and "Juvenile dermatomyositis and other idiopathic inflammatory myopathies: Epidemiology, pathogenesis, and clinical manifestations".)

While the initial presentation of systemic autoimmune diseases may be subtle, they can be distinguished from JPFS based on the presence of objective findings on examination (eg, rash, synovitis, muscle weakness), as well as laboratory abnormalities (eg, autoantibodies, cytopenias, elevated ESR, CRP, and/or muscle enzymes). As discussed above, we generally reserve antinuclear antibody (ANA) testing for scenarios where there is a specific concern for an ANA-related autoimmune disease. (See 'Diagnostic testing' above.)

•Chronic noninfectious osteomyelitis (CNO)/chronic recurrent multifocal osteomyelitis (CRMO) – CNO/CRMO is an autoinflammatory disorder that can cause multifocal bone inflammation and pain. It may affect one or more areas and has a predilection for certain bones, including the long bones (especially in the lower extremities), pelvis, spine, clavicle, and mandible. Affected areas are typically tender and, when they are superficial, may be associated with visible swelling (eg, clavicular swelling). CNO/CRMO is associated with other autoimmune and autoinflammatory conditions including spondylarthritis, psoriasis, and inflammatory bowel disease. (See "Chronic nonbacterial osteomyelitis (CNO)/chronic recurrent multifocal osteomyelitis (CRMO) in children".)

In contrast to patients with JPFS, those with CNO/CRMO often have focal tenderness over affected bones, sometimes with associated swelling or warmth, and experience relief with NSAIDs. Some patients with CNO/CRMO may have elevated inflammatory markers (ie, ESR and CRP), and bony lesions can be detected on magnetic resonance imaging (MRI); these tests are all normal in patients with JPFS.

Patients with rheumatic diseases may develop comorbid JPFS [20,61,62], although pain should never be attributed to JPFS if there is ongoing rheumatic or other disease activity. An overview of fibromyalgia in the setting of rheumatic diseases is provided separately. (See "Overview of chronic widespread (centralized) pain in the rheumatic diseases".)

CLASSIFICATION AND DIAGNOSTIC CRITERIA — 

Multiple sets of criteria and tools have been developed for patients with fibromyalgia. The Yunus and Masi diagnostic criteria are often used clinically to diagnose patients with juvenile primary fibromyalgia syndrome (JPFS). By contrast, the 2010 American College of Rheumatology (ACR) classification criteria are typically reserved for research purposes. While the ACR criteria were developed for adults with fibromyalgia, they are also sensitive and specific for adolescent patients with JPFS [69]. More information on various criteria and tools is provided below:

●Yunus and Masi criteria for JPFS – The Yunus and Masi criteria for JPFS are commonly used clinically to diagnose JPFS and are summarized in the table (table 3) [24]. They differ from the ACR criteria in requiring the presence of at least five tender points; the 1990 ACR criteria require 11 tender points, while the subsequent 2010 update does not require any. The criteria were published in 1985 based on a review of 33 children with JPFS (mean age 15 years, range 9 to 17 years).

●ACR criteria for fibromyalgia – Several different classification schema have been proposed to identify adults with fibromyalgia for research and epidemiologic purposes. The ACR criteria were initially published in 1990 [21] and revised in 2010, as shown in the figure (figure 3) [22]. The 2010 ACR criteria may be used as an alternative to the Yunus and Masi criteria for adolescent patients with JPFS. One study examined these two criteria schemes in 47 adolescent patients with JPFS (mean age 15 years old, range 11 to 17 years) and 48 age- and sex-matched patients who had chronic, localized pain [69]. When compared with the Yunus and Masi criteria as a gold standard, the 2010 ACR criteria had an 88 to 89 percent sensitivity and specificity for diagnosing JPFS. The 2010 ACR criteria have not been validated in younger children with JPFS [8]. The use of these criteria in adults is discussed separately. (See "Fibromyalgia: Clinical manifestations and diagnosis in adults".)

●Pain and Symptom Assessment Tool (PSAT) – PSAT was developed to facilitate classification of adolescents with JPFS based upon the 2010 ACR criteria [70]. The measure contains 72 items and takes approximately five minutes to complete. It comprises two subscales: the Widespread Pain Index (the number of pain locations) and the Symptom Severity Scale (focusing on central elements of fatigue, tiredness, and concentration/memory difficulties, as well as the presence of other common somatic symptoms). Data are still emerging on its clinical sensitivity and utility in clinical trials [20].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Fibromyalgia".)

SUMMARY AND RECOMMENDATIONS

●Definition – Juvenile primary fibromyalgia syndrome (JPFS) is a chronic condition that is characterized by chronic and diffuse musculoskeletal pain and a range of other symptoms and comorbid conditions, such as fatigue, nonrestorative sleep, chronic headaches, and mood disturbances or disorders. When working with patients and families, providers may describe JPFS as a type of central sensitization to better highlight the underlying defect in pain processing. (See 'Introduction' above and 'Terminology' above.)

●Epidemiology – JPFS is relatively common, affecting an estimated 1 to 6 percent of school-aged children and adolescents worldwide. The age of onset of JPFS is typically in the early to middle adolescent years, and it is virtually nonexistent in children <4 years old. There is a strong female predominance. (See 'Epidemiology' above.)

●Etiology and pathogenesis – While the exact etiology and pathogenesis of this disorder are unknown, JPFS is thought to be largely driven by "central pain sensitization," where nociceptive neurons in the central nervous system become more responsive to normal or lower-than-normal afferent input. JPFS may be more likely to occur in genetically susceptible persons, possibly in response to environmental triggers. (See 'Etiology' above and "Pathogenesis of fibromyalgia".)

●Clinical presentation – By definition, patients with JPFS have chronic, widespread pain. They may also experience a variety of other symptoms such as fatigue, headache, and mood or sleep disturbances, which in some cases indicate the presence of an overlapping comorbid condition (table 2). (See 'Common symptoms and comorbidities' above.)

•Diffuse, widespread pain – The cardinal manifestation of JPFS is diffuse musculoskeletal pain which may affect the joints, muscles, and other soft tissues of the arms, legs, back, and neck. Pain is often moderate to severe and constant, without predictable fluctuations during the day or night. Pain is not usually relieved by nonsteroidal antiinflammatory drugs (NSAIDs) and may be worsened by factors including exercise or physical or mental stress. (See 'Diffuse, widespread pain' above.)

•Physical findings – The physical examination for patients with JPFS is most notable for the absence of findings that suggest alternative diagnoses (eg, arthritis, enthesitis, myopathy). Patients may have tender points, which are highly localized areas of the body that are consistently sensitive to pressure (figure 1). Patients often exhibit hyperalgesia (ie, increased pain response to painful stimuli) and/or allodynia (ie, pain from a nonpainful stimulus). (See 'Physical findings' above.)

●Evaluation and diagnosis

•When to suspect fibromyalgia – JPFS should be suspected in older children (typically >9 years old) who have chronic (typically >3 months), diffuse, widespread pain that impacts their daily activities and is associated with other symptoms that commonly accompany JPFS (eg, headache, fatigue, sleep or mood disturbances). (See 'When to suspect fibromyalgia' above.)

•History and physical examination – The history in children suspected of having JPFS is focused on excluding alternative diagnoses as well as assessing the extent of symptoms and the subsequent psychosocial impact. The physical examination should be comprehensive, with the goal of evaluating for any objective findings (eg, synovitis, muscle weakness) that suggest alternative causes of pain.

•Diagnostic testing – There are no specific laboratory or imaging tests that are diagnostic of fibromyalgia. In most patients, we send a limited set of laboratory tests including a complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), basic metabolic panel, and thyroid-stimulating hormone (TSH). We do not routinely test for rheumatoid factor (RF) or antinuclear antibodies (ANA). Imaging of painful areas is rarely indicated. (See 'Diagnostic testing' above.)

•Establishing the diagnosis – JPFS is a diagnosis of exclusion that can be made clinically based on the presence of typical symptoms and examination findings in the absence of findings that suggest an alternative diagnosis. We use the Yunus and Masi diagnostic criteria (table 3) as part of the clinical evaluation. (See 'Establishing the diagnosis' above and 'Classification and diagnostic criteria' above.)

●When to refer – We refer patients who are suspected of having JPFS to a pediatric rheumatologist or pediatric pain specialist for diagnostic evaluation and management. (See 'When to refer' above.)

●Differential diagnosis – Important alternative diagnoses to consider in the evaluation of JPFS include complex regional pain syndrome (CRPS) type 1, growing pains, thyroid dysfunction, and rheumatic diseases. Differences in clinical features usually distinguish fibromyalgia from these other disorders. (See 'Differential diagnosis' above.)