Growing pains

INTRODUCTION — "Growing pains" generally refer to recurrent, self-limiting episodes of limb pain in children of preschool and early school age, usually affecting the lower extremities. These pains occur late in the day and are frequently nocturnal, awakening the child from sleep. While worrisome and distressing to parents/caregivers when severe and frequent, these pains when correctly diagnosed are benign, are not associated with functional disabilities, and resolve or decrease in severity and frequency in the second decade of life. The etiology is still unknown, but these pains probably have multiple causes and represent heterogeneous conditions with a common clinical pattern for which management may differ. It is important to accurately diagnose and use the term "growing pains" correctly with parents/caregivers in order not to overlook other diseases and conditions causing limb pain that may result in damage and disability to children.

This topic reviews the definition, epidemiology, hypotheses related to the etiology and pathogenesis, clinical manifestations, the differential diagnosis, evaluation, management, and prognosis of growing pains. The evaluation of children with a limp, joint pain, and/or swelling is discussed separately. (See "Evaluation of limp in children" and "Evaluation of the child with joint pain and/or swelling".)

TERMINOLOGY — The term "growth diseases" (maladies de la croissance) and later "growing pains" were coined in the 19^th century to describe lower limb pains in young children [1,2]. Attempts to change the taxonomy of growing pains to "idiopathic/benign nocturnal pains of childhood" or "recurrent limb pains/aches of childhood" have largely failed, despite the knowledge that these pains do not relate to actual growth [3,4].

DEFINITION — There is no consensus regarding the definition of growing pains or validated diagnostic/classification criteria (see 'Diagnosis' below). However, several definitions have been proposed (table 1A-C) [5-11]. Relatively consistent features include bilateral, intermittent pain in the legs that occurs primarily late in the day or at night but resolves by morning, with absence of joint involvement, redness, tenderness, swelling, and limp [12,13]. The physical examination is normal with the exception of minor structural findings such as hyper- or hypomobility and a pronated foot posture. Children with unexplained pains that are exclusively unilateral or focal, are worse after rest, occur in association with specific activities, or are accompanied by other systemic symptoms should not be diagnosed with growing pains and deserve further investigation. (See 'Diagnosis' below and 'Differential diagnosis' below and 'Evaluation' below.)

EPIDEMIOLOGY — The prevalence of growing pains varies from 1.24 to 57 percent [5,12,14-22], and growing pains are the most common cause (14 to 87 percent) of episodic musculoskeletal pain in children [14,23-25]. The variation among studies depends upon the population studied, the age of the children, the method of ascertainment, the setting surveyed (community, school, clinic, community or tertiary hospital), and the definition used for growing pains.

Growing pains are generally slightly more common among girls than boys [14,17,18], although one study found a slightly higher prevalence in boys [22].

The most common age is between 3 and 12 years. In general, the prevalence of growing pains decreases in children older than 10 years of age [15,26], but one study showed an increased prevalence in children at 13 years of age compared with 5 year olds [24].

The prevalence may be higher in children with background medical conditions, as observed in children with congenital heart disease and cleft palate [27,28].

There may be a geographic variation. As an example, a higher prevalence seen in Australia (37 percent) compared with the prevalence in North and Northeast India (1.24 to 2.1 percent) [18,20,22].

PROPOSED ETIOLOGIES

Overview — The etiology of growing pains is not known. Historically, they were felt to be due to the rapid linear growth of bones, which occur at night, thus "explaining" why the pain often occurs at night. However, this hypothesis is not accepted, as the maximal prevalence of growing pains does not occur during periods of rapid growth, and one study did not find an increase in the rate of growth one year prior to and two years after diagnosis [4]. In addition, the pain is not described or localized to the major sites of growth (the epiphysis of long bones or the spine) [12,29].

Growing pains probably represent a common clinical entity resulting from diverse causes. The most frequently studied hypotheses are genetics, mechanical factors such as hypermobility and foot/leg posture, local overuse possibly associated with reduced bone strength, hypovitaminosis D, a noninflammatory pain syndrome, and a possible relationship with restless legs syndrome. However, systematic reviews of these studies found significant heterogeneity among them, limiting the validity of the proposed etiologies [3,30].

Genetics — There is a high prevalence of growing pains among parents and siblings, especially monozygotic twins, of children probands [5,6,11,18,31-33]. In addition, there may be an association of growing pains with restless leg syndrome, which also has a strong genetic component (see 'The relationship with restless legs syndrome' below and "Restless legs syndrome and periodic limb movement disorder in children"). Per a systemic review of etiology and pathogenesis studies, genetics is probably the strongest factor associated with growing pains [30]. However, formal genome association studies have yet to be performed.

Mechanical factors

Hypermobility — Two studies have found a strong correlation between hypermobility and growing pains, with as many as 61 percent of patients with growing pains fulfilling criteria for hypermobility and as many as 42 percent of patients with hypermobility exhibiting growing pains-like symptoms [34-36]. However, another study did not find this association [25]. (See "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder".)

Other lower limb and foot mechanical factors — Decreased ankle dorsiflexion strength and genu valgus are associated with growing pains [37,38]. However, the relevance of the association between growing pain and foot and leg posture (eg pronation/supination and genu varum/valgum) has been disputed [39-42]. (See "Forefoot and midfoot pain in the active child or skeletally immature adolescent: Overview of causes", section on 'Flexible pes planus (flat feet)'.)

Overuse/decreased bone strength — Children with growing pains often report greater symptoms following an increased level of physical activity [5,19,32]. A study of bone speed of sound (SOS), measured by ultrasonography and used as an alternative measure of bone strength, provides support for local overuse as a contributing factor. In this study, children with growing pains had decreased bone SOS measured at the mid-tibia and radius compared with control children [43]. Decreased bone density is seen in patients with other forms of local overuse [44]. In a five-year follow-up study of this cohort, there was an improvement in bone SOS, and no correlation was found between youth with residual growing pains and bone SOS. However, those youth with a bone SOS Z-score lower than -1 continued to have growing pains [45]. Another study showed increased bone SOS (measured at the first finger distal phalanx metaphysis) and decreased pain after vitamin D supplementation [46].

Vitamin D deficiency — Several cross-sectional studies have shown a high prevalence of vitamin D deficiency in children with growing pains, with one study showing that 94 percent of the children with growing pains were deficient in vitamin D [38,46-48]. However, these studies did not include a control group from the general population. A case-control study did not find a difference in vitamin D levels between 386 children with growing pains and 399 controls [49]. In addition, a study performed in a sunny region of the United States (Florida) did not find this association; only 14 percent of the children with growing pains in this study were deficient in vitamin D [50]. (See "Vitamin D insufficiency and deficiency in children and adolescents", section on 'Other symptoms'.)

Two observational studies investigating the effect of vitamin D supplementation on pain found an association between vitamin D supplementation and decreased pain intensity [46,51]. (See 'Management' below.)

Noninflammatory pain syndrome — Growing pains may represent a noninflammatory pain syndrome. One study found a low pain threshold in response to pressure of tender points associated with fibromyalgia in children with growing pains compared with controls [52]. In a five-year follow-up study, a lower pain threshold continued to correlate with ongoing growing pains, but none of the patients developed other pain syndromes [26]. This finding was confirmed by another group who found increased somatosensory responses in children with growing pains, including low pain threshold and increased responses to cutaneous cold, vibration, and deep pressure stimuli [53]. Older observational data suggest an association with other pain syndromes (eg, headaches, abdominal pain) and emotional factors [5,12,14,17,54,55].

The relationship with restless legs syndrome — There is a debate as to whether growing pains and restless legs syndrome are separate entities [56,57] or related clinical syndromes on a spectrum of lower limb pain and discomfort [58-64]. Many children fit the definition of both syndromes [60]. However, restless legs syndrome has validated diagnostic criteria while growing pains do not [7,65]. Use of painful legs with a strong urge to move them as an exclusion factor for growing pains may decrease the diagnostic overlap of these conditions [11]. The coexistence of these syndromes is seen within families, suggesting a common genetic effect [6]. (See "Restless legs syndrome and periodic limb movement disorder in children".)

Other factors — Other factors found to be associated with growing pains include increased body mass index and perinatal factors such as prematurity, small head circumference, low birth weight (<3000 g), and shorter height (<50 cm) [32,37,66]. One study did not find an association between growing pains and vascular perfusion changes assessed by technetium-99 bone scans in painful regions of children with growing pains compared with control children who underwent this scan for other causes [67].

CLINICAL FEATURES — While there is no formal validated definition for growing pains, the common clinical features are well described [5,12,14,17,31,32,51,68-75].

Location — Growing pains occur primarily only in the lower extremities. However, upper extremities may also be painful in some patients.

The pain is usually bilateral, although it can be unilateral during individual episodes, with the pain alternating between extremities. When localized to only one limb, it is necessary to search for an alternative diagnosis. (See 'Differential diagnosis' below.)

The pain is usually nonarticular and is typically located in the thighs, calves, popliteal fossa, or shins.

The physical examination during and after the episodes is normal.

Type and severity of pain — The pain is described in older children as having a deep, achy, or crampy character. The severity ranges from mild to severe enough to cause the child to cry. However, activities and function are rarely limited.

Timing and duration — The pain occurs primarily in the late afternoon, evening, or nighttime hours and may awaken the child from sleep. It usually resolves by morning, but some patients have mild daytime complaints. The frequency of episodes is variable. Typically, they occur at least once a week, but, in severe cases, they may occur daily. However, symptom-free periods of days, weeks, or even months may occur. In order to diagnose growing pain, episodes must recur for at least three months. However, pain episodes often continue for years and occasionally persist into adolescence. The frequency and severity of episodes usually decrease at older ages [26].

Triggers — Often, parents/caregivers can predict the occurrence of a painful episode on days of increased physical activity, excessive fussiness or fatigue of the child, or following a night of poor sleep.

Response to treatment — Pain is relieved by massage, heat, or common analgesics, such as acetaminophen, ibuprofen, or naproxen.

Other symptoms and findings — Children often complain of recurrent abdominal pain and/or headaches. Some children may exhibit hypermobility, genu valgus, flexible pes planus, pronated foot posture, or conversely tight tendons [35,37,66].

EVALUATION — The evaluation of children who complain of recurrent, self-limited lower-extremity pain should include a complete history and physical examination. If there are no concerning signs for other conditions (table 2), laboratory and imaging tests are not necessary (algorithm 1).

History — The history should characterize the pain episodes, other symptoms, and a family history (see 'Clinical features' above):

●Pain characteristics:

•At what age did the painful episodes start?

•How often do these episodes occur?

•Where is the pain? Is the pain bilateral or unilateral? Is the pain in the joint, muscle, or bone? Is it localized or diffuse?

•What does the pain feel like (for older children; eg, cramps, achiness, discomfort)?

•What times of the day does the pain occur?

•Does it awaken the child at night? If yes, how long after the child falls asleep? (This question may have implications for therapy; for example, whether to consider used of naproxen rather than ibuprofen since it is longer acting.) (See 'Management' below.)

•Does the child feel an urge to move the leg?

•Is there pain or stiffness in the morning?

•Does the child limp?

•What triggers the pain (eg, increased activity, tiredness, poor sleep, stresses, excitement such as birthdays or vacations)? Can painful episodes be predicted in advance of their occurrence? Parental/caregiver use of a diary may be help answer this question.

•Is there a specific activity that causes pain?

•Does the pain or muscle tiredness occur during or immediately after exercise? Does rest improve the pain? Is there a history of rhabdomyolysis (suggests a metabolic myopathy)?

•How long does the pain last?

•How severe is the pain? Does the child cry or scream? Is the pain worsening over time?

•What makes the pain better (eg, massage, warm compresses, medication, movement of the legs)?

•Does it affect the child's activity and/or function (eg, running, jumping, sports, playing), gait, sleep, or school attendance?

•Do pain episodes occur around events that the child may wish to avoid (eg, school days, with fewer episodes on weekends)?

●Other symptoms or exposures:

•Are there any other symptoms (eg, fever, swelling, erythema, fatigue, malaise, weight loss, rashes, eye redness/pain)?

•Does the child have recurrent headaches or abdominal pain?

•Is there muscle weakness?

•Is there a history of recent illness (eg, viral infection, group A streptococcal infection)?

•Is there a recent history of travel (eg, to a region endemic to Lyme disease)?

●Family history:

•Is there a family history of medical problems (eg, familial Mediterranean fever [ask on the origin/ethnicity of the family], sickle cell anemia, metabolic or bone disease, rheumatologic disorders)?

•Is there a family history of growing pains or other types of pain (eg, fibromyalgia, migraine headaches, irritable bowel syndrome, or unexplained extremity pain)?

•Is there a family history of hypermobility?

●Other questions:

•How was the child's development (specifically gross motor milestones)?

•Is there adequate intake of calcium and vitamin D? Is the child's diet restricted (eg, lack of fruits and vegetables)?

•Does the child have emotional or behavioral difficulties or anxieties?

•Are there specific stressors at home or school (both for the child and parents/caregivers)?

●Parent/caregiver questionnaires – Two parental/caregiver questionnaires have been developed for evaluation of children with extremity pain for growing pains, with the authors reporting good to excellent validity and reliability [76,77]. One of them, used as a screening tool, consists of nine questions evaluating pain localization, intensity, and 24-hour temporal distribution [77].

Physical examination — A careful physical examination must be performed to exclude other conditions in the differential diagnosis. It is important to note whether the findings are focal, unilateral, bilateral, or diffuse.

●Musculoskeletal examination:

•Examine the gait. An abnormal gait is seen in a variety of musculoskeletal disorders but should not be present in a child with growing pains. (See "Evaluation of limp in children".)

•Assess for hypermobility. If present, determine whether it is generalized (using the Beighton score) or localized.

•Examine for mechanical abnormalities (eg, genu valgus, pes planus with a pronated posture of the foot, leg-length discrepancies).

•Evaluate muscle strength and examine for atrophy.

•Examine joints, enthesis, and soft tissue for local warmth, erythema, swelling, tenderness or pain on motion, decreased range of motion, and point tenderness upon bone compression. These may indicate an orthopedic, infectious, or rheumatologic condition (eg, juvenile idiopathic arthritis [JIA]).

•Palpate for tender points (eg, for fibromyalgia).

●Examination of other systems – Additional findings may suggest infection; rheumatologic (eg, dermatomyositis, systemic lupus erythematosus, vasculitis, or psoriasis), infectious, neurologic, or hematologic disease; or malignancy.

•General appearance, such as ill, wasted, or febrile (may indicate any of the causes listed above). As an example, an ill or wasted appearance may indicate an underlying malignancy.

•Skin rashes or lesions (often present in children with rheumatologic, infectious, or hematologic diseases and in some genetic conditions such as angiokeratoma in Fabry disease).

•Lymphadenopathy or splenomegaly (malignancy, infection, or rheumatic disease).

•Neurologic examination for neuropathies and muscle or metabolic conditions.

Additional evaluation

●Indications for additional evaluation – Additional evaluation is indicated in children who have concerning symptoms and signs in order to exclude more serious conditions in the differential diagnosis (table 2). The most important symptoms and signs include:

•Systemic symptoms (eg, unexplained fever, weight loss, fatigue, or malaise)

•Unilateral or focal pain

•Persistent (chronic, nonepisodic) pain; increasing limb pain, even if episodic

•Pain in the morning

•Limp or limitation of function and activities

•Localized findings on examination (decreased range of motion, warmth, tenderness, swelling, erythema)

•Lack of pain in the lower extremities

●Tests to perform – Additional evaluation should include at least a complete blood count and differential and an erythrocyte sedimentation rate and/or C-reactive protein. Abnormal results in these tests exclude a diagnosis of growing pains. Supplementary laboratory tests (eg, for rheumatologic, infectious, metabolic, hematologic disorders) and imaging tests, including the choice of the appropriate modality, are individualized and based upon the clinical presentation and physical findings.

●When additional evaluation is not indicated – Further evaluation is not warranted in children with a history consistent with growing pains, normal physical examination, and no concerning symptoms and signs for other conditions [75,78]. Ordering screening tests can be reassuring to parents/caregivers who remain concerned despite normal physical findings during clinic visits. However, extensive testing entails the possibility of a false-positive result that leads to further unnecessary testing. Scheduling a follow-up visit for reassessment, including offering guidance on when to return for reevaluation, is the preferred alternative to ordering further investigations.

Most studies have shown normal inflammatory indices and bone markers (calcium, phosphorus, alkaline phosphatase), negative rheumatoid factor, and normal imaging (radiographs and technetium-99 bone scans) in children with growing pains [5,47,78], with the exception of one study showing mildly elevated levels of alkaline phosphatase in many children with growing pains [4]. There is debate whether vitamin D levels are decreased in children with growing pains. Measurement of vitamin D levels solely for the evaluation of growing pains is not indicated.

DIAGNOSIS — There are no validated diagnostic criteria for growing pains, although several have been proposed (table 1A-C) [5-11]. The poor consistency and incomplete reporting of important demographic and clinical data among studies of growing pains preclude validation of these criteria [13]. As a result, the diagnosis of growing pains is still one of exclusion (algorithm 1).

A machine learning Random Forest model based on 16 demographic, clinical, and laboratory items was developed to enable a web-based diagnosis of growing pains with 98 percent accuracy (the gold standard was expert physician diagnosis of growing pains) [79]. However, this model was developed in tertiary pediatric rheumatology centers with most controls having inflammatory disease, thus affecting generalization to patients seen in primary medicine settings. In addition, the model necessitated measuring acute phase reactants.

Other conditions that cause limb pain should be ruled out, at least by history and physical examination, prior to the diagnosis of growing pains. Concerning symptoms and signs for other conditions need to be further evaluated by laboratory and/or imaging tests (see 'Differential diagnosis' below and 'Evaluation' above). Children who have a typical presentation with no symptoms concerning for other conditions and a normal general physical and musculoskeletal examination can be diagnosed with growing pains.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of episodic lower-extremity pain includes numerous diseases and conditions (table 3). They include inflammatory/rheumatologic, metabolic, hematologic, and orthopedic conditions as well as tumors and malignant diseases, infections, genetic diseases, noninflammatory pain syndrome, and effects of trauma [75,80]. It is important to exclude these conditions, some of which can be life threatening or result in irreversible damage as a result of a delayed diagnosis. If the diagnosis is unclear, it is crucial to continue following the child in clinic. A comprehensive history and physical examination can exclude the vast majority of these conditions. Concerning symptoms and physical findings warrant further evaluation (table 2). (See 'Evaluation' above.)

Several of the conditions that can closely mimic clinical features of growing pains include:

●Nonsystemic categories of juvenile idiopathic arthritis – Children with the oligoarthritis, polyarthritis, and psoriatic arthritis categories of juvenile idiopathic arthritis (JIA) may present with a limp and/or pain and inflammation of one or more joints. Systemic manifestations (other than uveitis and psoriatic rash or nail changes) are characteristically absent. Most types of arthritis are associated with typical physical findings in the joints including swelling, tenderness, and limitation of motion. However, enthesitis related arthritis, seen more commonly in males older than eight years of age and associated with human leukocyte antigen (HLA) B27, can present with bilateral lower limb pains. They often describe localized heel and/or buttocks pain. There is usually tenderness and sometimes swelling at the enthesis sites of the lower extremities, pelvis region, and sacroiliac joints. Some children with enthesitis related arthritis may only have tenderness on palpation of their lower-extremity enthesis, without joint swelling, but they usually have more pain and loss of function after rest, including morning stiffness, than children with growing pains. (See "Oligoarticular juvenile idiopathic arthritis" and "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications" and "Spondyloarthritis in children".)

●Familial Mediterranean fever – This genetic autoinflammatory disease is caused by pathogenic variants in the MEFV innate immunity regulator, pyrin (MEFV) gene encoding the pyrin protein. Familial Mediterranean fever is seen mainly among Mediterranean populations (particularly Sephardic Jews, Arabs, Turks, and Armenians) and is characterized by recurrent, one- to three-day episodes of fever, abdominal pain, chest pain, and arthritis with increased inflammatory markers. One of the major features is exertional leg pain/myalgia, occurring in up to 58 percent of patients [81,82]. These pains resemble growing pains in that they occur primarily late in the day and are usually bilateral pain in the calves and thighs. Unlike growing pains, the pain is often severe enough to interfere with function and requires use of antiinflammatory or other analgesic medications. In familial Mediterranean fever, these pains may represent an enthesopathy. One study showed that 30 percent of patients with familial Mediterranean fever with exertional leg pain also fulfilled diagnostic criteria for growing pains compared with 6 percent of those without exertional leg pain [83]. Thus, children with growing pains from populations at high risk of developing this condition, especially those with a family history, should undergo evaluation for this disease. (See "Clinical manifestations and diagnosis of familial Mediterranean fever".)

●Chronic nonbacterial osteomyelitis – This condition is a chronic autoinflammatory bone disorder of unknown cause (there are rare genetic variants). Almost any bone in the body can be affected, especially the metaphysis of the long bones of the lower extremities, the pelvis, vertebra, clavicle, ribs, and mandible. Some patients have associated psoriasis, especially palmoplantar pustulosis. Inflammatory markers are usually normal or mildly elevated. Radiographs occasionally display lytic or sclerotic lesions. Whole-body magnetic resonance imaging (MRI) showing bone marrow edema is the gold standard for diagnosis. Bone biopsies are often necessary to exclude other causes, including malignancies. Various types of antiinflammatory therapies are used, depending on the severity of the disease and location of the lesions. This condition can be quite difficult to suspect and diagnose because the onset of the disease and pain is often insidious and frequently in the lower limbs, with occasional night pain, mimicking growing pains. (See "Chronic nonbacterial osteomyelitis (CNO)/chronic recurrent multifocal osteomyelitis (CRMO)".)

●Metabolic disorders – Several metabolic diseases may mimic growing pains:

•Rickets – Rickets refers to severe vitamin D deficiency or other calcipenic or phosphopenic conditions that cause deficient mineralization of bone, especially at the growth plates before its closure. Typical clinical and radiologic features as well as elevated alkaline phosphatase can aid in diagnosis. Patients may present with lower limb pain that resembles growing pains. (See "Overview of rickets in children".)

•Scurvy – Scurvy, caused by a deficiency in vitamin C, can also result in lower limb pain ranging from mild to refusal to bear weight. In addition, patients can develop purpura and gingival hemorrhage. There are typical radiographic findings, and MRI can show signs of periostitis and bone marrow edema, mimicking chronic nonbacterial osteomyelitis. Inflammatory markers can be elevated; thus, scurvy can also mimic rheumatic conditions such as JIA and vasculitis [84]. Scurvy is usually seen in patients with developmental delay, autism, and eating disorders with vitamin C-deficient diets. Scurvy should be suspected in those such patients who present with lower limb pains. (See "Overview of water-soluble vitamins", section on 'Vitamin C (ascorbic acid)' and "Micronutrient deficiencies associated with protein-energy malnutrition in children", section on 'Ascorbic acid'.)

•Glycogen storage diseases – Glycogen storage disease, especially McArdle disease (type V) with autosomal recessive inheritance, causes postexertional pain that may mimic growing pains [85]. Patients may develop rhabdomyolysis. (See "Myophosphorylase deficiency (glycogen storage disease V, McArdle disease)".)

●Fibromyalgia – Fibromyalgia is a noninflammatory central pain sensitization syndrome of unknown etiology characterized by chronic diffuse musculoskeletal pain, nonrestorative sleep, fatigue, concentration difficulties, autonomic nervous system dysfunction, and other symptoms in multiple body systems. Unlike growing pains, the pain is widespread rather than primarily in lower extremities, chronic rather than episodic, and seen throughout the day. There are multiple other symptoms. Physical findings include the presence of tender points. The effect on daily function can be substantial. Fibromyalgia is predominately seen in adolescent females and can be quite difficult to treat, with nonpharmacologic and limited pharmacologic interventions. Nonsteroidal antiinflammatory drugs are not effective. In one series, 20 percent of children with fibromyalgia were initially diagnosed with growing pains [86]. There are limited data assessing whether children with growing pains are at risk of developing fibromyalgia, but one small series of children with growing pains followed into adolescence did not find any patients who developed fibromyalgia [26]. (See "Fibromyalgia in children and adolescents: Clinical manifestations and diagnosis".)

●Hypermobility syndrome – Hypermobility can cause lower-extremity pain that may mimic growing pains. These is controversy as to whether children with growing pains have a higher prevalence of hypermobility than the general pediatric population and if children with hypermobility have a higher prevalence of growing pains (see 'Hypermobility' above). Between 10 to 20 percent of all children fulfill criteria for hypermobility, more often among females, with a deceasing prevalence in older children. Generalized hypermobility can be diagnosed by the Beighton score (modified in younger children by examining ankle dorsiflexion instead of back flexion). Hypermobility can be isolated or part of the Ehlers-Danlos syndrome or other collagen/soft tissue disorders, many of them genetic. A family history is common. Soft tissue abnormalities in other systems may accompany genetic hypermobility syndromes, including the skin, blood vessels, heart valves, eyes, and bones. Children with pain related to hypermobility are usually treated with physical therapy and orthotics. (See "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder".)

●Trauma (particularly stress fractures or overuse) – Most types of trauma are easily differentiated from growing pains, but stress fractures that can develop insidiously as a result of overuse may mimic growing pains as the pain is often localized to the shins, increases with activity, and can be bilateral. Physical examination may show focal tenderness at the site of the fracture. Often not seen in regular radiographs, stress fractures can be demonstrated by technetium-99 bone scan. (See "Overview of stress fractures".)

●Bone tumors, leukemia, and neuroblastoma – Bone tumors can be difficult to distinguish from growing pains since tumor pain often occurs at night. Nocturnal pain occurs most often with osteoid osteoma. Since this tumor secretes prostaglandins, the pain responds dramatically to use of nonsteroidal antiinflammatory drugs. Other primary bone tumors, such as Ewing sarcoma, can also present with nocturnal pain. Unlike growing pains, the bone pain associated with tumors is unilateral. Patients with bone tumors also may have a palpable mass, may occasionally have tenderness to pressure, and can have secondary muscle atrophy. (See "Clinical presentation, staging, and prognostic factors of Ewing sarcoma" and "Nonmalignant bone lesions in children and adolescents", section on 'Osteoid osteoma'.)

Approximately 25 to 30 percent of children with leukemia or neuroblastoma present with musculoskeletal pain, which can be bilateral and localized to the lower extremities [87]. However, unlike growing pains, these children usually have systemic symptoms and often appear ill with fever, pallor, petechiae, or weight loss. Laboratory tests, imaging, and bone marrow biopsy can assist in the diagnosis of these diseases. (See "Overview of common presenting signs and symptoms of childhood cancer".)

●Orthopedic conditions – Many orthopedic conditions can cause lower-extremity pain, and a few examples that may mimic growing pains include:

•Osteochondritis dissecans and osteochondrosis (calcaneal apophysitis, Sever disease, tibial tuberosity avulsion, Osgood-Schlatter disease) – These conditions can mimic growing pains, especially when they occur bilaterally in the lower extremities [88,89]. They are more common among highly active and athletic school-age children and young adolescents, particularly males. Usually, patients have localized pain and tenderness at the heels in calcaneal apophysitis and above the tibia tuberosity in tibial tuberosity avulsion. In the latter, bone swelling may be apparent. The diagnoses can be confirmed by radiographs. (See "Osteochondritis dissecans (OCD): Clinical manifestations, evaluation, and diagnosis" and "Heel pain in the active child or skeletally immature adolescent: Overview of causes" and "Osgood-Schlatter disease (tibial tuberosity avulsion)".)

•Osteonecrosis (eg, Legg-Calvé-Perthes disease) – Legg-Calvé-Perthes disease is a syndrome of idiopathic osteonecrosis (avascular necrosis) of the hip. It typically presents as insidious onset of hip pain and/or limp and occurs mainly in males between the ages of 3 to 12 years. Legg-Calvé-Perthes can be bilateral in 10 to 20 percent of children and therefore mimic growing pains [90]. Physical examination shows a limited range of motion of the hips. The diagnosis is confirmed by various modalities of imaging. (See "Approach to hip pain in childhood", section on 'Legg-Calvé-Perthes and secondary avascular necrosis'.)

●Infection – The vast majority of infections are localized to one region or extremity and can easily be distinguished from growing pains. Children usually manifest other symptoms, such as fever (which can be low-grade in hematogenous osteomyelitis), malaise, irritability, decreased appetite, or decreased activity. Physical signs include focal findings of joint, bone or muscle inflammation (warmth, swelling, point tenderness), and limitation of function (eg, limp, limited use of extremity, lack of ambulation) (see "Hematogenous osteomyelitis in children: Clinical features and complications" and "Hematogenous osteomyelitis in children: Evaluation and diagnosis"). Conditions such as viral or postinfectious polymyalgia, such as after streptococcal infection, can cause bilateral lower-extremity pain, although there is usually a marked effect on function. (See "Overview of viral myositis".)

●Fabry disease – This X-linked recessive genetic disease is caused by pathogenic variants in the galactosidase alpha (GLA) gene, encoding the alpha-GAL enzyme that helps break down sphingolipids. The condition can cause lower-extremity neuropathic pain that can mimic growing pains, including pain that worsens following physical activity [91-93]. The pain is usually severe and affects the distal part of the extremities more than in classic growing pains in males. Female carriers may have a mild form of this disease and less severe pain [91]. Misdiagnosis of growing pains can result in delayed diagnosis and initiation of treatment with the potential development of neurologic and kidney damage. Other important features of Fabry disease are the presence of angiokeratomas, leg edema, hypohidrosis, corneal opacities, and proteinuria. (See "Fabry disease: Clinical features and diagnosis".)

●Restless legs syndrome – Restless legs syndrome is an important differential diagnosis of growing pains, and, frequently, children with extremity pains fulfill the diagnostic criteria of both entities (see 'The relationship with restless legs syndrome' above). This syndrome is characterized by an urge to move the legs, usually accompanied by discomfort or unpleasant sensations. Symptoms are worse at rest and during inactivity and almost always occur in the evening and night. There is often periodic limb movement at night and a poor quality of sleep. There is commonly a family history. Iron deficiency is a frequent finding. There are some clinical and laboratory differences, which may aid in contrasting the two conditions. Growing pains are more episodic and are not associated with low iron or ferritin levels and usually do not persist beyond childhood or mid-adolescence. Restless legs syndrome is associated with more discomfort than pain and usually includes the urge for leg movement to maintain comfort [7,11,65,94]. (See "Restless legs syndrome and periodic limb movement disorder in children".)

MANAGEMENT — There is a paucity of controlled or even observational studies for treatment of growing pains. Thus, many of the management principles are based upon clinical experience and expert opinion.

General principles

●Education and reassurance of the benign nature of growing pains and the good long-term outcome. This is a crucial part of the management plan as it can alleviate unnecessary concern and further medical work-up.

●Recognition of the child’s pain on one hand while empowering the parents/caregivers to encourage the child to continue their usual activities, social experiences, and school attendance. Discontinuation of activities should be discouraged because it does not prevent painful episodes and may increase related anxieties.

●Acknowledgement that growing pains, especially the related frequent nocturnal awakenings, can affect parental/caregiver quality of life even more so than the child, who often vaguely remembers awakening.

Acute pain relief — Approaches to acute pain relief include nonpharmacologic or pharmacologic means, such as massage and application of local heat in various forms and over-the-counter analgesics (eg, acetaminophen or ibuprofen). The author usually first tries nonpharmacologic interventions and then uses intermittent pharmacologic therapy if those measures are not successful. Some children resist massage during episodes, and episodes are often too brief to assess the actual benefit of medication. Pain management in children is discussed in greater detail separately. (See "Pain in children: Approach to pain assessment and overview of management principles", section on 'Nonpharmacologic interventions' and "Pain in children: Approach to pain assessment and overview of management principles", section on 'Pharmacologic therapy'.)

Preventive treatment — For children who awaken at night due to pain, we suggest preventative administration of analgesics before bedtime in two situations:

●When parents/caregivers can predict the development of episodes, such as after a day of strenuous activity, fussiness, fatigue, stress, or poor sleep the prior night.

●When clusters of nightly or nearly nightly painful episodes occur. Administering analgesics before bedtime for one to two weeks and, in rare cases, longer courses may help break this cycle, allowing both the child and the parent/caregiver to have adequate sleep. In children who awaken more than four hours after going to bed, it may be more useful to administer a long-acting nonsteroidal antiinflammatory drug after dinner (eg, naproxen, meloxicam) rather than over-the-counter analgesics (eg, ibuprofen).

Other proposed treatments — Other treatments that have been studied include vitamin D and iron supplementation, muscle stretching exercises, and orthotics.

●Vitamin D supplementation – Three uncontrolled cohort studies have evaluated the effect of vitamin D supplementation in children with growing pains [46,51,95]. In one study, 120 children with growing pains and a 25-hydroxyvitamin D level <20 ng/mL were given a single oral dose of vitamin D (dose: 150,000 international units for children ≤6 years of age or 300,000 international units for older children) with calcium supplementation (dose:1000 mg/day) for one month. The mean visual analog pain level decreased significantly after three months parallel to an increase in vitamin D levels [51]. In the second study, 33 children with a 25-hydroxyvitamin D level <30 ng/mL received once-monthly high-dose vitamin D supplementation for three months (the dose varied according to level of insufficiency/deficiency) [46]. Eight patients had no further pain episodes after 3 and 24 months of follow-up. This study also found a significant increase in bone strength assessed by ultrasound speed of sound (SOS) at 24 months. Neither study examined other variables such as episode frequency, nocturnal awakening, and the effect on quality of life. In the third study, a one-time dose of 60,000 international units of vitamin D3 and a daily dose of 600 international units for three months with calcium 50 mg/kg/day were administered to 218 children. Vitamin D levels were not measured prior to treatment. Only 28.8 percent of the 160 patients followed for three months experienced resolution of their pains. However, 67.3 percent of 115 patients with a hemoglobulin level less than 11 g/dL who received in addition iron supplementation of 3 mg/day for three months had resolution of their pains [22]. (See "Vitamin D insufficiency and deficiency in children and adolescents".)

●Physical therapy – One unblinded study examined the effect of muscle stretching exercises in 18 children with growing pains compared with 16 controls not referred for these exercises. Muscle stretching was associated with a more rapid resolution of symptoms compared with controls, with exercisers having a mean of zero episodes per month by nine months, while children in the control group continued to have one to two episodes per month at the end of the 18-month observation period [96]. Another uncontrolled study of 110 children with growing pains managed with three stretching exercises for the adductors, knee extensors, and hamstrings in addition to analgesics and physical therapy found an associated decrease in growing pains [97].

●Orthotics – For children with growing pains and overpronation of the feet (pes planus or flexible flat feet), orthotics may provide some improvement in pain, though they generally do not alter the course of pes planus [41,42]. This is discussed in greater detail separately. (See "Forefoot and midfoot pain in the active child or skeletally immature adolescent: Overview of causes", section on 'Flexible pes planus (flat feet)'.)

PROGNOSIS — The prognosis of growing pains is generally good, with a decrease in episodes and resolution of these pains during the second decade of life. However, some children continue to have episodes of pain that are lower in frequency and intensity during adolescence [26,98]. Historic and more contemporary studies have not found that children with growing pains are at a higher risk of developing generalized pain syndromes such as fibromyalgia or other rheumatic conditions [26,99,100].

SUMMARY AND RECOMMENDATIONS

●Definition and clinical features – Growing pains refer to recurrent, self-limited episodes of limb pain, usually affecting both lower extremities, in children of preschool and early school years (table 1A-C). These pains occur late in the day and are frequently nocturnal and awaken the child from sleep. There is an absence of substantial musculoskeletal abnormalities, and these pains do not affect usual activities and function. (See 'Introduction' above and 'Definition' above and 'Clinical features' above.)

●Epidemiology – Growing pains are the most common condition causing episodic lower-extremity pain in children, occurring in an estimated 10 to 20 percent of school-aged children. (See 'Epidemiology' above.)

●Etiology – The etiology of growing pains is unknown, but it is likely that these pains have multiple causes and represent several conditions with a common clinical pattern. Several proposed hypotheses include a genetic predisposition, mechanical abnormalities such as hypermobility, an overuse syndrome with possible decreased bone strength, and a noninflammatory pain syndrome associated with a low pain threshold. Despite the name, growing pains are not related to the physical growth of the child. (See 'Proposed etiologies' above.)

●Diagnosis – The diagnosis can usually be made clinically in a child with a typical presentation who is otherwise healthy. However, it is important to take a careful history and perform a complete physical examination to differentiate growing pains from other, more serious conditions (algorithm 1). (See 'Diagnosis' above and 'Differential diagnosis' above and 'History' above and 'Physical examination' above.)

●Differential diagnosis – The diagnosis is unlikely to be growing pains if there are symptoms or physical signs concerning for other conditions, particularly if the child has systemic symptoms or appears ill, complains of pain in the morning or during the day, or has pain that is unilateral or focal pain, interferes with function or activity, or worsens or persists. Screening tests in these patients should include a complete blood count and differential and erythrocyte sedimentation rate and/or C-reactive protein. Abnormal results in these tests exclude a diagnosis of growing pains. Further testing and imaging are individualized based upon the clinical presentation and physical findings (table 2). (See 'Differential diagnosis' above and 'Additional evaluation' above.)

●Management – A key part of the management of growing pains is providing education and reassurance to children and parents/caregivers, including guidance on when to return for reevaluation. Nonpharmacologic modalities (eg, heat, massage, muscle stretches) and analgesics (eg, acetaminophen, ibuprofen) are used as needed for acute pain relief. For children who awaken at night due to pain with a predictable pattern (eg, occurring after a day of strenuous activity, fussiness, fatigue, stress, or poor sleep or occurring in clusters of nightly or nearly nightly painful episodes), we suggest preventative administration of analgesics (eg, acetaminophen, ibuprofen, naproxen) before bedtime (Grade 2C). (See 'Management' above.)

●Prognosis – The prognosis is good, with a decrease in pain episodes over time and resolution in most children during the second decade of life. (See 'Prognosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thomas JA Lehman, MD and Sarah Ringold, MD, MS, who contributed to earlier versions of this topic review.