A 14-year-old boy with a past medical history of prematurity (triplet born at 33 weeks, with uncomplicated neonatal intensive care unit treatment course) presented to the pediatric rheumatology clinic for evaluation of widespread musculoskeletal pain. He had been in his usual state of good health until about 4 months prior to the visit, when he developed an abrupt-onset cough, rhinorrhea, and malaise, accompanied by a low-grade fever. Over the course of 10 to 14 days, his upper respiratory symptoms and rash subsided. However, fatigue and malaise persisted, and he also developed myalgias and arthralgias.
The myalgias and arthralgias persisted and worsened over subsequent weeks. He describes the pain as “everywhere.” Pain is rated at 7 on a 10-point scale. The pain is characterized as primarily aching, sometimes with a burning or tingling quality. Pain is present in all four limbs but worst in the knees, shoulders, back, and wrists. He denies joint swelling or morning stiffness. Pain is always present, but worsens with activity. He is able to ambulate unassisted but cannot climb stairs. His mother has rented a wheelchair for him from a medical supply company; he uses this on the rare days he is able to attend school.
He also notes headaches that are moderate in intensity, not awakening him from sleep and not associated with visual changes or vomiting. Ibuprofen was unhelpful for his musculoskeletal pain. Naproxen did alleviate headaches but was ineffective for the musculoskeletal pain. Although he does not awaken at night due to pain, his sleep is unrefreshing and he feels profoundly fatigued and sleepy upon awakening. He has not attended school for most of the past month due to pain, fatigue, and malaise.
During his examination, the following results were noted: temperature, 36.7°C; weight, 85.3 kg (95th percentile); height, 178 cm (90th percentile); blood pressure, 128/64 mm Hg; heart rate, 87 beats per minute; and respiratory rate, 16 breaths per minute. He looks tired, but does not appear to be in distress. He is cooperative and responds appropriately to questions. With the exception of the musculoskeletal assessment, his comprehensive physical examination was unremarkable. He had full range of motion of all joints with no joint swelling, but complained of pain, particularly of the elbows, wrists, fingers, knees, and ankles, and also had mild tenderness of the posterior calf muscles. Tenderness was noted over the bilateral mid-trapezius muscles, scapulae, occipital prominences, medial elbows, and medial knees.
A complete blood count test demonstrated a white blood cell count of 6.9 K/mcL (48% neutrophils, 34% lymphocytes, 11% monocytes), hemoglobin of 16 g/dL, hematocrit of 46.2%, and platelets of 240 K/mcL. The erythrocyte sedimentation rate was 16 mm/h, and C-reactive protein was <0.3 mg/dL. A complete metabolic panel was unremarkable. Creatinine kinase and lactate dehydrogenase were normal at 99 U/L and 163 U/L, respectively. Thyroid stimulating hormone and free T4 were within normal limits.
Assessment and Recommendations
As our patient did not have joint swelling or restricted range of motion, and laboratory studies were unremarkable, the probability of an inflammatory disease, such as juvenile arthritis or lupus, was negligible. He was diagnosed with juvenile fibromyalgia, possibly initially triggered by a viral infection. The diagnosis was based on persistence of severe musculoskeletal pain in widespread body areas with normal laboratory studies and normal physical examination with the exception of tender points. Supporting evidence for the diagnosis included poor sleep, chronic headaches, severe fatigue, and frequent neuropathic quality of pain (tingling, numbness).
The patient was referred to an intensive, multidisciplinary adolescent pain-management program, incorporating physical therapy, exercise therapy, psychotherapy, and family therapy. He was prescribed 300 mg of oral gabapentin twice per day to provide some pain relief until he could begin the program. He was encouraged to continue attending school as much as possible. Unassisted ambulation was encouraged, but school attendance was prioritized; wheelchair use was to be permitted if essential to his school attendance. His parents met with school administrators to develop a plan for gradual return to school, with provision for extra tutoring to ameliorate school-related anxiety.
Three months later, following 6 weeks of participation in the intensive program, he reported ongoing widespread musculoskeletal pain. However, he was attending school daily without the use of the wheelchair, and was noting some gradual improvements in his sleep quality and fatigue.
Fibromyalgia is a common pediatric problem. Adolescents are most frequently affected, with up to 6.2% of adolescents meeting diagnostic criteria in some populations.1 Social and academic performance can be profoundly compromised, limiting patients’ development at a crucial life stage. Moreover, early onset chronic pain can be long lasting: in one study, 17% of adults with severe chronic pain reported onset in childhood or adolescence.2 Early identification and treatment of this disorder is crucial to avoid unnecessary diagnostic testing and restore patients’ normal functioning.
Juvenile primary fibromyalgia syndrome was first described by Yunus and Masi3 in 1985 in a series of 33 patients. The authors’ proposed diagnostic criteria comprised widespread pain in >3 areas for >3 months without evidence for an alternative etiology, along with at least 5 of 18 tender points, as well as 3 minor criteria (Table 1 and Table 2). Young people with fibromyalgia frequently report a panoply of associated symptoms. Profound fatigue and nonrefreshing sleep are nearly universal. Intermittent patchy numbness, most often of the distal extremities, is common and may lead to excessive testing including neuroimaging and electromyography. Subjective, patient-reported periarticular soft tissue swelling may be noted, but objective joint inflammation (warmth, swelling, decreased range of motion) is absent. Functional syndromes affecting nonmusculoskeletal systems are often present, particularly irritable bowel syndrome, chronic headache, and orthostatic intolerance or POTS (postural orthostatic tachycardia syndrome). Depression and anxiety may precede musculoskeletal symptoms or may develop later, as a consequence of the dysphoria and dysfunction that accompany chronic pain. Children with fibromyalgia may benefit from evaluation by a rheumatologist, physiatrist, and/or psychiatrist. Additionally, involvement of a neurologist, gastroenterologist, or cardiologist may be needed for assistance in managing nonmusculoskeletal symptoms. A multidisciplinary chronic pain program can be invaluable, but few such programs are available. In the absence of an established chronic pain program, primary pediatricians have a crucial role—not only in diagnosing fibromyalgia but also in coordinating the multispecialty care team.
Minor Criteria for Juvenile Primary Fibromyalgia Syndrome
Typical Fibromyalgia Tender Points
Juvenile fibromyalgia is a complex problem, necessitating a multidisciplinary approach to treatment. The biopsychosocial model of illness, as posited by psychiatrist George Engel in 1977,4 provides a helpful construct for understanding juvenile fibromyalgia. This model emphasizes that an individual’s illness experience is influenced not only by biologic and physiologic dysfunction, but also by psychosocial factors. Fibromyalgia is sometimes misconstrued as an entirely psychosomatic syndrome given the absence of objective findings on laboratory studies or clinical examination. The biologic basis of fibromyalgia has been well established by an extensive body of research. However, each patient’s pain experience is transmitted through the filter of his or her cultural, social, and psychologic milieu.
With regard to the biology of chronic pain, abnormalities in pain transmission at many levels have been observed in fibromyalgia sufferers. Alterations in nociceptive transmission in patients with fibromyalgia have been observed in ascending pathways, descending pain-modulating pathways, and in central pain perception. Ascending pain signals travel from peripheral nociceptive nerves (A-delta and C fibers) to synapse in the dorsal horn of the spinal cord. Chronic pain induces persistent stimulation and hypersensitization of these dorsal horn neurons. Hyperexcitable spinal pathways, in turn, transmit pain signals to the brain in response to low-level, normally nonpainful stimuli, or even in the absence of stimuli. Hyperalgesia (exaggerated pain response to mildly painful stimuli) and allodynia (painful response to nonpainful stimuli) are the clinical results.5
Abnormalities of descending pain modulation pathways have also been demonstrated in individuals with fibromyalgia. The periaqueductal gray-rostral ventromedial medulla (PAG-RVM) system is the neuroanatomic locus of this analgesic function. In patients with fibromyalgia, the PAG-RVM system is biased toward pain facilitation rather than inhibition. Serotonergic, noradrenergic, and endogenous opioid signaling pathways participate in descending pain modulation.6 Polymorphisms in the COMT (catechol-O-methyltransferase) gene, which degrades catecholamines, and in the mu-opioid receptor, have shown associations with risk for chronic widespread pain.7 These neurotransmitters likely mediate response to some types of antidepressants in patients with fibromyalgia.8
At the level of the cortex, brain studies such as functional magnetic resonance imaging and magnetic resonance spectroscopy have shown alterations in multiple areas, particularly the rostral anterior cingulate cortex (rACC). Decreased function of the rACC correlated with duration of fibromyalgia symptoms as well as the severity of comorbid depression.9 This linkage between anatomic brain changes and affective symptoms illustrates the multilayered complexity of fibromyalgia.
Psychosocial risk factors for fibromyalgia include mood disorders, anxiety disorders, abuse, trauma, poor family function, and poor pain-coping behavior by a parent. The heritability of chronic widespread pain has been estimated at 50%.10 This risk likely represents a composite of genetic factors, familial dysfunction related to chronic illness, and modeling of poor pain-coping behaviors. Parents of children with fibromyalgia are significantly more likely than controls to be diagnosed with chronic pain conditions themselves.11 Catastrophizing and poor perceived self-efficacy are cognitive patterns associated with poor pain coping in children as well as in parents. Depressive symptoms predict poor school attendance in adolescents with fibromyalgia, even more so than pain intensity or fatigue. Moreover, adolescents who are bullied at school or who have learning disabilities may develop a pattern of school avoidance, which can perpetuate a cycle of pain and poor coping skills.12
The treatment of fibromyalgia is multidisciplinary and individualized, typically incorporating medication, psychologic support, regular exercise, and physical therapy. Pain relief is of course one goal of treatment, but promotion of coping skills allowing resumption of usual activities despite ongoing pain is at least as important. Pharmacologic treatment for fibromyalgia has only modest efficacy. Patients and parents should understand that medication alone is unlikely to bring about satisfactory improvement. However, medication can be useful in improving sleep, easing depression and anxiety, and decreasing pain intensity to promote participation in nonpharmacologic treatment modalities such as exercise and counseling.13 The primary pharmacologic treatments for fibromyalgia include analgesics, antidepressants, and anticonvulsants. Among analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed as first-line therapy. Unfortunately NSAIDs are usually ineffective for fibromyalgia, although they can be helpful for comorbid causes of musculoskeletal pain such as osteochondroses or sports injuries. Opioids are best avoided for fibromyalgia due to poor efficacy and potential for dependence. Moreover, opioids may actually suppress endogenous opioid production, exacerbating pain amplification. Tramadol, a mu-opioid receptor agonist that also has an inhibitory effect on serotonin and norepinephrine reuptake, appears to be more effective and has a superior side effect profile compared to traditional opioids.14 Overall, however, analgesics are of limited utility for fibromyalgia and are generally used for as-needed adjunctive treatment along with anticonvulsants or antidepressants.
Gabapentin, and the related molecule pregabalin are the anticonvulsants most frequently prescribed for fibromyalgia. The mechanism of action is unclear but likely involves decreased neuronal excitation and enhanced inhibition. The efficacy of gabapentin is statistically significant compared to placebo but clinically modest for the majority of patients. About half of adult patients experienced a 30% or greater decrease in pain on pregabalin. The most frequent adverse effects of both pregabalin and gabapentin are somnolence, dizziness, and weight gain.15
Several classes of antidepressants have been shown to exert an independent effect on pain. Tricyclic antidepressants (TCAs) have shown modest effect for fibromyalgia. Typically, low doses of TCAs are given at bedtime. Interestingly, low-dose TCAs appear to be more effective for fibromyalgia than higher doses. The efficacy of TCAs in fibromyalgia appears to be time-limited with many patients experiencing tachyphylaxis after several months.16 Trazodone is another option to alleviate dysfunctional sleep. In an open-label study of adult fibromyalgia patients, trazodone improved sleep and decreased fatigue and stiffness, but had limited effect on pain.17 Traditional selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine or sertraline have minimal effect on pain but may be useful for treatment of comorbid depression. The combined serotonin-norepinephrine reuptake inhibitors (SNRIs) duloxetine and milnacipran are US Food and Drug Administration-approved for fibromyalgia in adults. These agents have shown some efficacy, although slight, for chronic pain, and a possible benefit for fibromyalgia-related cognitive deficits (“fibro fog”).18 SSRIs and SNRIs are associated with suicidality particularly in adolescents, and must be used cautiously and with close monitoring in this age group. Direct involvement with psychiatry is recommended in patients who are treated with these medications. With these caveats in mind, the SSRIs and SNRIs can be useful alternatives to anticonvulsants for young people with fibromyalgia.
In addition to medication, psychologic interventions, sleep hygiene, and exercise are the key elements of a multidisciplinary treatment plan for juvenile fibromyalgia. Education, cognitive-behavioral therapy (CBT), and sometimes family therapy or traditional individual psychotherapy may play a role. Patient education regarding the pathophysiology of pain amplification can be a therapeutic intervention in itself. Many fibromyalgia patients are extremely frustrated after experiencing months of severe pain of unclear cause. The provider must assiduously avoid implying that the patient’s pain is not “real” due to the absence of objective pathology. The provider should empathetically explain that fibromyalgia is a well-described syndrome and that treatment is possible, and provide reassurance regarding the absence of worrisome alternative diagnoses such as autoimmune disease or malignancy. This kind of physician-patient communication can effectively reduce patient and family anxiety and improve motivation to participate in a multidisciplinary treatment plan.
Among the psychologic interventions for fibromyalgia, CBT is the best studied. CBT involves structured instruction in avoiding catastrophizing, promoting positive pain-coping behavior using strategies such as distraction, and resuming normal function even with persistent pain. A 2011 randomized controlled trial of CBT versus fibromyalgia education alone for juvenile fibromyalgia showed much greater functional gains in the CBT group at 6 months.19 CBT was also well accepted by the adolescent patients and their parents. Unfortunately, access to CBT for adolescents with chronic pain is often limited by a lack of trained practitioners. Family counseling can be useful in identifying and reducing parental pain-reinforcing behaviors and in decreasing overall family stress. Other forms of psychotherapy, such as traditional individual psychotherapy, may be indicated for patients with significant comorbid affective disorders, anxiety disorder, or other psychiatric diagnoses.
Fatigue and nonrefreshing sleep are major problems for most fibromyalgia patients.20 Sleep deprivation causes increased somatic symptoms even in otherwise healthy adults, and therefore must be addressed in fibromyalgia. Sleep problems reported by fibromyalgia patients include insomnia, nonrestorative sleep, and frequent awakenings. Comorbid sleep disturbances such as restless leg syndrome and sleep apnea should be identified and treated. Finally, patients should be educated regarding sleep hygiene, including such measures as regular sleep/wake times, avoiding napping, minimizing caffeine, and avoiding use of smartphones/screens in late evening.21
Exercise has long been included in recommendations for fibromyalgia treatment. Exercise reduces somatic symptoms even in healthy people and is hypothesized to increase descending pain-inhibitory central nervous system pathways. Many types of exercise have been evaluated. Of course the specific exercise prescribed will depend on patient preference and available resources (such as a gym or pool) but there is some evidence to guide the design of an exercise plan. Aerobic exercise has by far the most evidence of efficacy. One large systematic review concluded that aerobic exercise appears effective at improving pain, fatigue, and quality of life, but did not improve sleep.22 Low-intensity, regular aerobic exercise is ideal. It is best to avoid recommending over-intense or overlong exercise as this can result in more severe postexercise symptoms. Patients should be advised to expect some mild increases in pain and fatigue as they habituate to regular exercise. Typical recommendations are for 20 to 30 minutes of low-intensity aerobic exercise such as walking, at least 3 times weekly. Strength and resistance training, although less well studied, may also be helpful. Based on current evidence, exercises focusing on flexibility alone are unlikely to be effective in reducing fibromyalgia symptoms.23
Although chronic noninflammatory pain does not lead to permanent joint or muscle damage and is not life-threatening, the impact of these pain syndromes should not be minimized. Fibromyalgia in young people frequently leads to poor school attendance and withdrawal from social activities. Patients’ social development and academic performance can be profoundly compromised during a crucial life stage. Fortunately, with thoughtful multidisciplinary treatment most young people with juvenile primary fibromyalgia can eventually regain normal function. Early and accurate diagnosis of young people with fibromyalgia is essential to enable patients to avoid inappropriate diagnostic testing and embark on an effective treatment plan.
- Buskila D. Pediatric fibromyalgia. Rheum Dis Clin North Am. 2009;35:253–261. doi:10.1016/j.rdc.2009.06.001 [CrossRef]
- Hassett AL, Hilliard PE, Goesling J, Clauw DJ, Harte SE, Brummett CM. Reports of chronic pain in childhood and adolescence among patients at a tertiary care pain clinic. J Pain. 2013;14(11):1390–1397. doi:10.1016/j.jpain.2013.06.010 [CrossRef]
- Yunus MB, Masi AT. Juvenile primary fibromyalgia syndrome. A clinical study of thirty-three patients and matched normal controls. Arthritis Rheum. 1985;28(2):138–145. doi:10.1002/art.1780280205 [CrossRef]
- Engel GL. The clinical application of the biopsychosocial model. Am J Psychiatry. 1980;137(5):535–544. doi:10.1176/ajp.137.5.535 [CrossRef]
- Nielsen LA, Henriksson KG. Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia): the role of central and peripheral peripheral sensitization and pain disinhibition. Best Pract Res Clin Rheumatol. 2007;21(3):465–480. doi:10.1016/j.berh.2007.03.007 [CrossRef]
- Kindler LK, Bennett RM, Jones KD. Central sensitivity syndromes: mounting evidence to link fibromyalgia with other common chronic pain disorders. Pain Manag Nurs. 2011;12(1):15–24. doi:10.1016/j.pmn.2009.10.003 [CrossRef]
- Holliday KL, McBeth J. Recent advances in the understanding of genetic susceptibility to chronic pain and somatic syndromes. Curr Rheumatol Rep. 2011;13(6):521–527. doi:10.1007/s11926-011-0208-4 [CrossRef]
- Marchand S. The physiology of pain mechanisms: from the periphery to the brain. Rheum Dis Clin North Am. 2008;34(2):285–309. doi:10.1016/j.rdc.2008.04.003 [CrossRef]
- Jensen KB, Srinivasan P, Spaeth R, et al. Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain. Arthritis Rheum. 2013;65(2):3292–3303. doi:10.1002/art.38170 [CrossRef]
- Holliday KL, McBeth J. Recent advances in the understanding of genetic susceptibility to chronic pain and somatic syndromes. Curr Rheumatol Rep. 2011;13(6):521–527. doi:10.1007/s11926-011-0208-4 [CrossRef]
- Anthony KK, Schanberg LE. Assessment and management of pain syndromes and arthritis pain in children and adolescents. Rheum Dis Clin North Am. 2007;33(3):625–660. doi:10.1016/j.rdc.2007.07.010 [CrossRef]
- Kashikar-Zuck S, Johnston M, Ting TV, et al. Relationship between school absenteeism and depressive symptoms among adolescents with juvenile fibromyalgia. J Pediatr Psychol. 2010;35(9):996–1004. doi:10.1093/jpepsy/jsq020 [CrossRef]
- Sarzi-Puttini P, Buskila D, Carrabba M, Doria A, Atzeni F. Treatment strategy in fibromyalgia syndrome: where are we now?Semin Arthritis Rheum. 2008;37(6):353–365. doi:10.1016/j.semarthrit.2007.08.008 [CrossRef]
- Sumpton JE, Moulin DE. Fibromyalgia: presentation and management with a focus on pharmacological treatment. Pain Res Manag. 2008;13(6):477–483.
- Siler AC, Gardner H, Yanit K, Cushman T, McDonagh M. Systematic review of the comparative effectiveness of antiepileptic drugs for fibromyalgia. J Pain. 2011;12(4):407–415. doi:10.1016/j.jpain.2010.09.007 [CrossRef]
- Nishishinya B, Urrútia G, Walitt B, et al. Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (Oxford). 2008;47(12):1741–1746. doi:10.1093/rheumatology/ken317 [CrossRef]
- Morillas-Arques P, Rodriguez-Lopez CM, Molina-Barea R, Rico-Villademoros F, Calandre EP. Trazodone for the treatment of fibromyalgia: an open-label, 12-week study. BMC Musculoskelet Disord. 2010;11:204. doi:10.1186/1471-2474-11-204 [CrossRef]
- Häuser W, Wolfe F, Tölle T, Uçeyler N, Sommer C. The role of antidepressants in the management of fibromyalgia syndrome: a systematic review and meta-analysis. CNS Drugs. 2012;26(4):297–307. doi:10.2165/11598970-000000000-00000 [CrossRef]
- Kashikar-Zuck S, Ting TV, Arnold LM, et al. Cognitive behavioral therapy for the treatment of juvenile fibromyalgia: a multi-site, single-blind, randomized controlled clinical trial. Arthritis Rheum. 2012;64(1):297–305. doi:10.1002/art.30644 [CrossRef]
- Ablin JN, Clauw DJ, Lyden AK, et al. Effects of sleep restriction and exercise deprivation on somatic symptoms and mood in healthy adults. Clin Exp Rheumatol. 2013;31(6 Suppl 79):S53–59.
- Spaeth M, Rizzi M, Sarzi-Puttini P. Fibromyalgia and sleep. Best Pract Res Clin Rheumatol. 2011;25(2):227–239. doi:10.1016/j.berh.2011.03.004 [CrossRef]
- Busch AJ, Schachter CL, Overend TJ, Peloso PM, Barber KA. Exercise for fibromyalgia: a systematic review. J Rheumatol. 2008;35(6):1130–1144.
- Hauser W, Klose P, Langhorst J, et al. Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a meta-analysis and systematic review of randomized controlled trials. Arthritis Res Ther. 2010;12(3):R79. doi:10.1186/ar3002 [CrossRef]
Minor Criteria for Juvenile Primary Fibromyalgia Syndromea
Subjective soft tissue swelling
Irritable bowel syndrome
Pain modulation by stress
Pain modulation by weather factors
Typical Fibromyalgia Tender Pointsa
Upper border of trapezius
Muscle attachments at lower border of scapula
2nd-3rd costochondral junction, lateral to sternum
Posterior iliac crest