Rudolph's Pediatrics, 22nd Ed.

CHAPTER 207. Musculoskeletal Pain Syndromes

Yukiko Kimura

With a prevalence as high as 15%, chronic pain is increasingly being recognized as a common problem in children and adolescents,1 but one that is still poorly understood. This chapter describes evolving concepts of several syndromes in which musculoskeletal pain is a prominent feature. Interestingly, these pain syndromes frequently have overlapping features. However, most children can be readily diagnosed by the typical pattern of somatic complaints and the salient physical findings specific to each syndrome.

GROWING PAINS

Growing pains occur in children between the ages of 3 and 12, and are characterized by intermittent nighttime nonarticular aching or pain most commonly in the legs. Recent prevalence estimates vary from less than 3%2 to as many as 36.9% in 4 to 6 year olds in Australia.3 An extension of the syndrome in adolescents and adults may include restless legs syndrome. In one recent population study, the prevalence of restless legs syndrome was found to be 1.9% in 8 to 11 year olds and 2% in 12 to 17 year olds; a history of growing pains and sleep disturbances was more common in the study population.4 Interestingly, restless legs syndrome also is reported to be common in patients with fibromyalgia, another pain syndrome which is described later in this chapter.5 The pathogenesis of growing pains is unknown. Despite the name, it is almost certainly not owing to growing.6 Perhaps this term is used because the condition occurs in children (who are always growing), and does not occur in adulthood (after cessation of growth). Recently, investigators have shown that children with growing pains may have increased pain sensitivity11 and decreased bone strength as measured by quantitative ultrasound.12

Growing pains are typically bilateral, usually occurring in the evening or at night, and not associated with limping or limited mobility. There is no history of trauma or infection, and objective findings are lacking on physical examination. The areas most frequently involved include the thighs, calves, and, occasionally, the forearms and trunk.

Parents of children with growing pains report no swelling, color changes, or warmth of the affected limb. The physical examination is unrevealing. X-rays and laboratory tests may be necessary to alleviate parental concern,13 but if the clinical picture is typical, they are not necessary. In contrast to patients with juvenile idiopathic arthritis (JIA), who usually have more pain and stiffness when first arising in the morning, these children are usually asymptomatic in the morning.

If the child has a limp, is complaining of pain in or around the joint, or has an abnormal musculoskeletal exam, growing pains is probably not the correct diagnosis. A thorough investigation for known causes of joint pain should be pursued, such as infection, inflammatory arthritis, and neoplasm, as well as orthopedic and endocrine disorders.

Treatment for this condition is symptomatic. Heat, massage, and analgesics such as nonsteroidal anti-inflammatory agents or acetaminophen, have all been suggested, but none have been tested in a prospective fashion. Reassurance that growing pains have no long-term sequelae and represent a relatively benign condition is important.

HYPERMOBILITY SYNDROMES

Hypermobility is widely prevalent in children and adolescents, and may be responsible for a wide variety of musculoskeletal complaints including benign joint hypermobility syndrome (BJHS), patellar subluxation, articular dislocation, premature osteoarthritis, and increased susceptibility to ligamentous injury. In addition to causing joint specific problems, BJHS is also now known to be associated with chronic pain, fatigue, and possibly dysautonomia in adults.14 Additional hereditary diseases that must be considered in the differential diagnosis of joint laxity include: (1) Ehlers-Danlos syndrome, (2) Marfan syndrome, (3) marfanoid hypermobility syndrome, (4) osteogenesis imperfecta, (5) Williams syndrome, and (6) inborn errors of metabolism such as homocystinuria and hyperlysinemia.

There is tremendous variability in the reported prevalence of joint hypermobility in the general population, with studies reporting incidences from as low as 2% to as high as 30%. Hypermobility appears to be more common in younger children and in females.15-18 There may be racial and ethnic differences as well. Estimates of the prevalence of hypermobility in children vary from 10% to 34%, declining during the school-aged years.19,20 The prevalence of pain in adults with BJHS varies between 5 to 45% depending upon the group studied.21,22 Children affected by BJHS are usually school-aged and adolescents, although patients under age 5 have been described. An increased incidence of a familial tendency for joint hypermobility has been reported. The parents may report that they were loose-jointed as youngsters.

FIGURE 207-1. Demonstrations of Beighton score components. (A) Extension of the wrist and metacarpophalangeal joints so that the fingers are parallel to the dorsum of the forearm. (B) Passive apposition of the thumb to the flexor aspect of the forearm. (C) Hyperextension of the elbows 10 degrees or more. (D) Hyperextension of the knees 10 degrees or more. (E) Flexion of the trunk with the knees fully extended so the palms rest on the floor.

DIAGNOSIS

The 1998 Revised Brighton Criteria23 are the most recently published criteria for hypermobility. The components of the Beighton score consist of five simple maneuvers: (1) extension of the wrist and metacarpophalangeal joints so that the fingers are parallel to the dorsum of the forearm; (2) passive apposition of the thumb to the flexor aspect of the forearm; (3) hyperextension of the elbows 10 degrees or more; (4) hyperextension of the knees 10 degrees or more; and (5) flexion of the trunk with the knees fully extended so the palms rest on the floor (Fig. 207-1). Patients are scored on a 9-point scale, with one point awarded for each hypermobile site. A Beighton score of 4 or more points fulfills criteria for hypermobility. However, the use of the Beighton score to diagnose hypermobility in children may not be optimal: since children are more hypermobile than adults, it may identify as many as 50% of children as being “abnormal” in terms of excessive hypermobility.

The other criterion for the diagnosis of BJHS are shown in Table 207-1. The examiner should also look for stigmata of heritable connective tissue diseases such as Marfan syndrome (Marfanoid habitus, arachnodactyly, high-arched palate, ocular abnormalities such as drooping eyelids and dislocated lens), and Ehlers-Danlos syndrome including increased elasticity of the skin, abnormal “papyraceous” scars, and a velvety texture of the skin (see Fig. 207-2).

CLINICAL MANIFESTATIONS

The symptoms attributed to BJHS include joint and muscle pain, transient joint swelling, and subjective stiffness; these are typically worsened with increased physical activity. The joints most commonly involved are the lower extremity joints, but the back also may be affected. If joint swelling is present, consideration must be given to an inflammatory arthropathy such as juvenile idiopathic arthritis. A high frequency of hypermobility was found in a group of children with recurrent episodes of joint pain that was called juvenile episodic arthritis/arthralgia.24 These children most likely simply have hypermobility syndrome, with the swelling likely owing to edema from strain and sprain injuries rather than true joint effusions.

Table 207-1 1998 Revised Brighton Criteria for Benign Joint Hypermobility Syndrome

Major Criteria

1. A Beighton score of 4 out of 9 or greater (either currently or historically)

2. Arthralgia for longer than 3 months in four or more joints

Minor Criteria

1. A Beighton score of 1, 2, or 3 out of 9

2. Arthralgia (≥3 months) in one to three joints or back pain (≥3 months), spondylosis, spondylolysis/spondylolisthesis

3. Dislocation/subluxation in more than one joint, or in one joint on more than one occasion

4. Soft tissue rheumatism, at least lesions (eg, epicondylitis, tenosynovitis, bursitis)

5. Marfanoid habitus (tall, slim, span/height ratio <1.03, upper: lower segment ratio less than 0.89, arachnodactyly (positive Steinberg/wrist signs)

6. Abnormal skin: striae, hyperextensibility, thin skin, papyraceous scarring

7. Eye signs: drooping eyelids or myopia or anti-mongoloid slant

8. Varicose veins or hernia or uterine/rectal prolapse

Pes planus, which becomes apparent on weight bearing, is also common in hypermobility and may cause musculoskeletal pain that tends to improve with the use of orthotics. Chronic nonspecific back pain may also be secondary to hypermobility, and can also predispose to injuries such as spondylolysis and spondylolisthesis.

FIGURE 207-2. Dermatological features of Ehlers-Danlos syndrome. (A) Increased skin elasticity. (B) Papyraceous scars.

Growing evidence suggests that hypermobility is not just a “benign” problem limited to the joints. One recent study of 15 children with BHJS found that these children had increased laxity of other tissues compared to asymptomatic prepubertal children.25 Furthermore, children and adults with BJHS tend toward osteopenia25,26 and there appears to be overlap of hypermobility with chronic pain, fatigue and dysautonomia, and fibromyalgia.27-30

A recent study of 125 children with BJHS found that 48% had “clumsiness,” poor coordination, developmental motor delay, major physical limitations, and school absences because of symptoms.31 Up to 20% had recurrent joint sprains and 10% had actual subluxation/dislocation of a joint, among many other features that overlapped with collagen abnormalities such as Ehlers-Danlos and Marfan syndromes.

DIAGNOSIS AND TREATMENT

Basic laboratory investigations, such as a complete blood count, erythrocyte sedimentation rate, serum chemistries, thyroid function tests, and urinalysis, are usually negative unless there is an underlying inflammatory condition. Joint radiographs show no evidence of joint space narrowing, osteopenia, or erosive change. Invasive studies, such as arthrocentesis, arthroscopy, or biopsy are not necessary.

The treatment of benign joint hypermobility syndrome includes (1) explanation of joint laxity and the mechanism of pain; (2) reassurance that an underlying arthritis does not exist; (3) analgesics; (4) a physical therapy program to improve periarticular muscle strength; and (5) avoidance of activities that aggravate the musculoskeletal pain. When overpronation and pes planus are present, the use of an orthotic to correct pronation and support the arch may be helpful in normalizing the gait and deceasing lower extremity joint symptoms.18 The intermittent use of nonsteroidal anti-inflammatory drugs (NSAIDs), or application of warmth or cold, may help relieve pain or stiffness in some patients. Swimming is an excellent sport to improve strength and cardiovascular endurance without excessive impact loading and strain on the supportive tissues, especially since exercise tolerance in children with benign joint hypermobility syndrome is reduced.32 The rehabilitation program should address both the physical and emotional needs of the child, and in severe cases, the child will benefit from a multidisciplinary approach involving physical and occupational therapy, psychology, and podiatry. The prognosis is thought to be good in most cases if benign joint hypermobility syndrome is identified early and interventions begun prior to the development of a chronic pain syndrome.

COMPLEX REGIONAL PAIN SYNDROME

Complex regional pain syndrome (CRPS) is characterized by pain, swelling, and disuse of an extremity associated with signs of vasomotor instability. This syndrome has had many names, including reflex sympathetic dystrophy (RSD), Sudeck atrophy, causalgia, reflex neurovascular dystrophy, and hysterical edema. The incidence of CRPS in children is not known, but the usual age of onset is between 9 and 15 years, and it is much more common in girls than boys.

Disorders precipitating complex regional pain syndrome in adult patients include infection, fracture, surgery, peripheral neuropathy, and trauma (mild to severe), but such conditions rarely antedate pediatric complex regional pain syndrome.33 Instead, the antecedent injury is usually relatively minor in relation to the severity of the complex regional pain syndrome. In one of the first series of pediatric complex regional pain syndrome, Bernstein reported that only 11 out of 24 (46%) of his cases in children had an antecedent illness or trauma.34 It is much more common in the lower extremities in children as compared to adult.35-37

The patient with complex regional pain syndrome often complains of a continuous burning sensation. Typically, even gentle stroking of the skin causes marked discomfort and withdrawal of the limb, a phenomenon referred to as allodynia, which is highly characteristic of complex regional pain syndrome. The limb is usually held in a spastic posture, and the patient refuses to move it actively or passively because of pain. The patient will usually refuse to bear weight on the affected extremity. There is often diffuse swelling of the distal extremity, and vasomotor changes, including coolness or warmth, pallor or erythema, and accompanying hyperhidrosis, are present. If the complex regional pain syndrome has been present for an extended period of time, the patient may develop trophic skin changes, with alterations in the nails, hair, and pigmentation.

The pathophysiology of this syndrome is unknown, but it appears to be owing in part to immobilization. The cause of the immobilization, which is usually self-induced, remains unclear. Several authors have reported that children with complex regional pain syndrome tend to demonstrate psychosocial stress or psychopathological trends, including a tendency to somaticize.38-41 Psychotherapy is therefore thought to be as an important therapeutic intervention in many patients.

As in other pain syndromes, laboratory studies are negative in this syndrome. Bone radiographs in the adult patient characteristically reveal a patchy osteoporosis, but children do not uniformly have demineralization, and when it occurs it is usually only diffuse, mild osteopenia. Arterial Doppler ultrasonography may show decreased flow on the affected side. Bone scintigraphy utilizing 99m Tc-labeled phosphate or polyphosphates may be abnormal, showing diffusely increased (and sometimes decreased) uptake in the juxta-articular tissues of the affected distal extremity. The MRI may show edema in the bones and/or marrow. These imaging abnormalities are not specific, and therefore they are not necessary to diagnose a patient with the typical signs and symptoms of complex regional pain syndrome.

Multiple treatment modalities have been suggested to break the pain cycle and to reduce increased sympathetic tone, but it is clear that early mobilization is the single most critical intervention. Therefore, the mainstay of treatment is physical therapy to encourage the child to use the affected limb.34,35,42,43 Immobilization is contraindicated and only aggravates the pain and edema. The family should be taught range-of-motion exercises that should be done frequently throughout the day. The regimen may include contrast baths with cold and heat application, and superficial desensitization techniques, such as rubbing or massaging. With aggressive therapy, many children with early complex regional pain syndrome are quickly able to resume weight bearing.

Psychotherapy, biofeedback, and cognitive behavioral therapy (CBT) may be efficacious in children who do not have rapid resolution with physical therapy, analgesics, and desensitization techniques. In most case reports and series, pediatric patients generally achieve complete resolution of their pain and disability with active physical therapy with or without cognitive behavioral therapy.34,36,39,40,42,43 The prognosis in children is generally good,35although relapses may occur at times of stress or following repeat trauma to the limb.

JUVENILE PRIMARY FIBROMYALGIA SYNDROME

Fibromyalgia is a common but poorly understood chronic pain condition characterized by widespread musculoskeletal aching, fatigue, and sleep disturbance. The prevailing theory of pathogenesis is that it is a dysregulation of pain pathways that lead to central pain sensitization, which is marked by neurohormonal, neurotransmitter, and sleep dysregulation. Fibromyalgia is often unrecognized or misdiagnosed in adults, but the situation is even worse for children, who often have symptoms for years before the diagnosis is made.50,51 In addition, skepticism and controversy over the existence of fibromyalgia continue because of the paucity of objective abnormalities in patients diagnosed with the condition. Despite the absence of characteristic physical, laboratory, radiographic, and pathologic findings, growing evidence supports the consensus that fibromyalgia is not a psychosomatic condition.52-56

Fibromyalgia is most commonly diagnosed in women from ages 20 to 50 and is reported to occur in as many as 2% of the general population.57,58 In children, it is most prevalent in 13-to 15-year-old girls but can occur in younger children; it has been reported in children as young as 5 years old.29,59 This pain syndrome was estimated to account for 7.5% of new-patient referrals to the U.S. pediatric rheumatology disease registry, reported in 1998.60 In large population-based studies, fibromyalgia or diffuse musculoskeletal pain similar to fibromyalgia is seen in 1.2% to 7.5% of children.61,62

CLINICAL FEATURES AND DIAGNOSIS

The diagnosis of this syndrome is based on the presence of diffuse aching, pain and stiffness, associated clinical features, and the demonstration of multiple tender points in the absence of other physical findings. The presence of true joint swelling or other physical abnormality mitigates against this diagnosis and should prompt further evaluation for an underlying inflammatory disorder, although one should bear in mind that fibromyalgia and rheumatic diseases not infrequently coexist.77 A complete blood count, erythrocyte sedimentation rate, rheumatoid factor test, antinuclear antibody test, muscle enzyme determination, and thyroid function tests are considered in most patients to exclude other conditions. X-rays of affected areas should be normal in fibromyalgia.

The definition of fibromyalgia requires chronic pain as well as stiffness in at least 3 body areas for a minimum of 3 months. The hallmarks of the physical examination are the absence of abnormal physical findings and the presence of tender points, which are well described and categorized in the literature (see Fig. 207-3). The presence of at least 11 of these tender points is defined by the American College of Rheumatology (ACR) as one of the criteria for fibromyalgia. The 18 tender points are identified by digital palpation over the following anatomic sites. The tender points are found in specific anatomic sites in periarticular structures, including the muscles, ligaments, entheses (tendon insertion sites), bursae, subcutaneous tissues, and bony prominences. The ACR criteria require 11 of 18 tender points (Table 207-2)63; however, the Yunus and Masi criteria, which may be more applicable to children, require only 5 tender points, with other associated symptoms (see Table 207-3).64

FIGURE 207-3. Tender points in fibromyalgia syndrome. Fibromyalgia tender points demonstrated on a child. Tender points in the low cervical region (1, 2) are bilateral, at the anterior aspects of the intertransverse spaces at C5–C7. At the second rib (3, 4), points are bilateral at the second costochondral junctions, just lateral to the junctions on upper surfaces. Tender points are found at the lateral epicondyle of the elbows (5, 6), bilateral 2 cm distal to the epicondyles, and at the knee (7, 8), bilateral at the medial fat pad proximal to the joint line. Occiput tender points (9, 10) are bilateral at the suboccipital muscle insertions. Trapezius points (11, 12) are bilateral, at the midpoint of the upper border, and points at the supraspinatus (13, 14) are bilateral at origins above the scapula spine near the medial border. Additionally, tender points at the gluteal (15, 16) are bilateral in upper outer quadrants of the buttocks in the anterior fold of the muscle. Those at the greater trochanter of the femur (17, 18) are bilateral, posterior to the trochanteric prominence. Control points (A, B, C) should not be tender. (Source: Reprinted with permission from Kimura, Yukiko, Pain in children with rheumatic diseases. Curr Rheumatol Rep. 2006;8(6):486, fig. 1.)

Patients typically complain of stiffness, especially in the morning, which when coupled with complaints of joint pain may cause confusion with arthritis. Patients may also report a subjective feeling of joint swelling, usually a diffuse transient puffiness in the hands and fingers, but objective joint swelling is not present. Non-restorative sleep (not feeling refreshed when first arising in the morning, even after adequate sleep) is a hallmark of this disorder. A sleep disturbance is common, especially difficulty with falling asleep and staying asleep, but some patients may not recognize their sleep alterations. Instead, the parents or roommate may have noticed frequent “tossing and turning” and awakening during the night. Interestingly, fibromyalgia appears to be associated with restless legs syndrome.5 Some patients complain that pain keeps them up at night. Studies show that adults with fibromyalgia have a significant disturbance of alpha wave activity in stage 4 nonrapid eye movement (NREM) sleep.65 A study of children with fibromyalgia confirmed that they also have sleep disturbances.66

Table 207-2 American College of Rheumatology Criteria for Diagnosis of Fibromyalgia Syndrome

Both criteria must be satisfied:

1. Widespread pain (bilateral, above and below the waist, and axial pain) present for at least 3 months

2. Pain (not tenderness) on digital palpation with 4 kg of pressure on 11 of the following 18 sites:

a. Occiput: at insertion of suboccipital muscle

b. Low cervical: at the anterior aspect of the intertransverse spaces of C7

c. Trapezius: at the midpoint of the upper border

d. Second rib: just lateral to the second costochondral junction at the upper rib border

e. Lateral epicondyle: 2 cm distal to the epicondyle

f. Gluteal: in the upper outer quadrant of the buttocks

g. Greater trochanter: posterior to the trochanteric prominence

h. Knees: at the medial fat pad proximal to the joint mortise

Data from Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33:160-172.

Additional associations include irritable bowel syndrome, migraine or tension headaches, paresthesias, Raynaud phenomenon, and dizziness attributed to postural orthostatic tachycardia syndrome (POTS) or neurocardiogenic orthostatic hypotension.67-69 Mood disturbances, especially depression, are common. Familial aggregation of fibromyalgia is common in adults70 as well as among children with fibromyalgia.71,72 Specific genetic polymorphisms in genes controlling serotonin, catecholamines, dopamine and other monoamines have been reported to modify the risk of developing fibromyalgia.55,56,73 In addition, there are a significant psychosocial, environmental, and family factors that may affect the development of fibromyalgia in children.74-76

Table 207-3. Yunus and Masi Criteria for Diagnosis of Fibromyalgia Syndrome in Children

All four major and three minor criteria, OR the first three major criteria, four painful sites, and five minor criteria, must be satisfied:

Major

1. Generalized musculoskeletal aching at three or more sites for 3 or more months

2. Absence of underlying condition or cause

3. Normal laboratory test results

4. Five or more typical tender points (see sites listed in 1990 ACR criteria)

Minor

1. Chronic anxiety or tension

2. Fatigue

3. Poor sleep

4. Chronic headaches

5. Irritable bowel syndrome

6. Numbness

7. Pain modulation by physical activities

8. Pain modulation by weather factors

9. Pain modulation by anxiety or stress

Data from Yunus MB, Masi AT. Juvenile primary fibromyalgia syndrome. A clinical study of thirty-three patients and matched normal controls. Arthritis Rheum. 1985;28:138-145.

TREATMENT

The physician should establish a supportive and understanding role with the patient and family in order to help guide the patient to recovery. The patient should be encouraged to accept responsibility for management of his or her pain. The management of fibromyalgia includes modalities to relieve pain, moderate but regular aerobic activities, improvement of sleep hygiene, returning to normal activities as much as possible, and emotional support. The first priority is to establish the diagnosis, and to reassure the patient and family that symptoms are not caused by arthritis or another mysterious and/or life-threatening disorder. An important point is that these patients must come to understand that the aim of treatment is to reduce pain, and most importantly, to allow the return to normal or near-normal activities, but that it may not be possible to completely eliminate the pain and discomfort associated with fibromyalgia.

Various nonmedical approaches to treatment have had variable success.78,79 Two approaches that have been studied in detail in adults and have been shown to be efficacious in children are exercise59,80-83 and cognitive behavioral therapy (CBT).84-89 CBT typically involves an 8 to 10 weekly sessions which usually include distraction, relaxation, and coping and stress-reduction techniques, as well as activity pacing, biofeedback, and self-hypnosis. In terms of exercise, a regular physical therapy program should be recommended for muscle stretching and strengthening, and a gradually escalating aerobic exercise program, which may include bicycling, walking, or swimming, should be suggested to recondition the patient.

Most reviews of existing studies agree that the combination of nonpharmacologic and pharmacologic interventions is most helpful in fibromyalgia in both adults58,87 and children.90 In terms of pharmacologic treatments, conventional analgesics such as nonsteroidal anti-inflammatory agents and acetaminophen are often prescribed but are rarely effective. Likewise, other analgesics, including narcotic analgesics, are not beneficial and should not be prescribed, except for possibly tramadol, for which there is some evidence of efficacy.91,92

Treatment with medications that alter neurotransmitter balance, such as antidepressants, has been found to be helpful for some patients. Low doses of a tricyclic antidepressant (TCA) such as amitriptyline at bedtime have been found to be useful,80,87,93,94 but the morning drowsiness and increased daytime fatigue that are sometimes a side effect of these medications may limit their usefulness. Other classes of antidepressants, for example, specific selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine95,96 and the more “balanced” serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine,97,98 have proved to be modestly effective in trials of adults with fibromyalgia. Recently, the use of pregabalin, a gamma-aminobutyric acid (GABA) agonist used in the treatment of neuropathic pain, has been found to be modestly effective in clinical trials, in adults.99,100