Best Practice & Research Clinical Rheumatology 28 (2014) 888e906

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Rheumatology
journal homepage: www.elsevierhealth.com/berh

The child with joint pain in primary care

Dr. E.S. Sen a, b, Dr. S.L.N. Clarke a, b, Prof. A.V. Ramanan a, *
a
Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Bristol, UK
b
School of Clinical Sciences, University of Bristol, Bristol, UK

a b s t r a c t
Keywords:
Juvenile idiopathic arthritis Joint pains are a common reason for children to present to primary
Septic arthritis care. The differential diagnosis is large including some diseases that
Perthes' disease do not primarily affect the musculoskeletal system. Although the
Slipped upper femoral epiphysis cause for many patients will be benign and self-resolving, in rare
Paediatric Gait, Arms, Legs, Spine (pGALS) cases the diagnosis is associated with long-term morbidity and
mortality if not detected early and appropriately treated. These
include primary and secondary malignancies, septic arthritis, oste-
omyelitis, inflammatory arthritis, slipped upper femoral epiphysis
(SUFE) and non-accidental injury. We highlight the importance of a
thorough history and directed yet comprehensive examination. A
diagnostic algorithm is provided to direct primary care physicians'
clinical assessment and investigation with the evidence base where
available. In many cases, tests are not required, but if there is sus-
picion of malignancy, infection or inflammatory conditions, labo-
ratory tests including full blood count, blood film, erythrocyte
sedimentation rate, C-reactive protein and lactate dehydrogenase
help to support or exclude the diagnosis. Autoimmune tests, such as
antinuclear antibodies and rheumatoid factor, have no diagnostic
role in juvenile idiopathic arthritis; therefore, we advise against any
form of ‘rheumatological/autoimmune disease screen’ in primary
care. Imaging does have a place in the diagnosis of joint pains in
children, with plain radiographs being most appropriate for sus-
pected fractures and SUFE, whilst ultrasound is better for the
detection of inflammatory or infective effusions. The appropriate
referral of children to paediatric rheumatologists, oncologists, or-
thopaedic surgeons and the emergency department are discussed.
© 2015 Elsevier Ltd. All rights reserved.

* Corresponding author. Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Upper Maudlin Street,
Bristol BS2 8BJ, UK. Tel.: þ44 0117 342 0149.
E-mail address: avramanan@hotmail.com (A.V. Ramanan).

http://dx.doi.org/10.1016/j.berh.2015.04.008
1521-6942/© 2015 Elsevier Ltd. All rights reserved.
 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906 889

Introduction

Musculoskeletal (MSK) symptoms are a common presentation of children to primary care and
emergency departments. Painful joints and/or limping are presenting features of a wide range of
conditions, many of which do not primarily affect the MSK system. Appropriate management requires
targeted history taking and directed yet comprehensive examination to narrow the differential diag-
nosis before selection of investigations. A practical approach considers the differentials filtered by the
age of the child, pattern of joint involvement and chronicity of symptoms. We will also highlight ‘red
flags’ pointing to serious conditions that may rarely be seen in primary care.
The overall prevalence of MSK pain during childhood has been estimated to be 25e50% [1e3]. In
many cases, this is benign and self-resolving; therefore, it is not brought to medical attention. However,
epidemiological surveys have highlighted that MSK complaints are a common presentation to primary
care representing around 7% of all paediatric attendances [4], and they are the third leading reason for
primary care presentation among adolescents in the USA [5]. In one study, MSK symptoms also rep-
resented 3% of paediatric day-case non-elective admissions [6]. A retrospective study in a paediatric
primary care clinic in Spain identified the prevalence of MSK pain increasing with age from 2.4 to 5.7%
at age 3 years to 27.5e36% at age 14 [7]. The most common presentations were knee arthralgias, other
joint arthralgias (ankles, wrists and small joints of the fingers) and soft tissue (muscles, ligaments and
tendons) pain comprising 65% of complaints across all age groups. Hip pain was reported significantly
more frequently in the preschool-age group, whereas heel and back pain was more common among
adolescents.
In this review, we will provide a guide to differential diagnosis through comprehensive and targeted
history taking and examination leading the reader to appropriate investigation and referral to sec-
ondary care.

The clinical approach

When faced with a child with joint pains in primary care, initial consideration of the range of
differential diagnoses will drive the appropriate history and examination. Although comparatively
uncommon, several diseases presenting with MSK symptoms can lead to mortality and long-term
morbidity; therefore, they should be actively considered and excluded. These include primary and
secondary malignancies, septic arthritis, osteomyelitis, inflammatory arthritis and non-accidental
injury/child abuse. Only one in 10,000 children have MSK pain as the primary presenting feature of
cancer [8], although around 20% of children with leukaemia and 2% of those with lymphoma have some
MSK symptoms at diagnosis [9,10]. By far, the most common cause for MSK pain in children presenting
to primary care in a Spanish study was trauma representing almost 44% of the presentations with
mechanical causes/overuse being the next frequent at 24% [7]. Transient synovitis and inflammatory
arthritis accounted for 2.5% and 0.8%, respectively.
The list of diagnoses presenting with MSK pain is large (Table 1). Many of these conditions are
discussed in further detail later in this review. A more practical approach categorises diagnoses by
patient age and anatomical distribution, whether generalised or localised to one or a few joints (Table
2). The chronicity of pain also assists with diagnosis: acute onset is likely to be associated with trauma;
subacute with infection, mechanical (e.g., osteochondroses) or orthopaedic (e.g., slipped upper femoral
epiphysis (SUFE)) causes; and chronic with malignancy, inflammation or non-inflammatory pain
syndromes [11]. Fig. 1 provides an approach to the main diagnoses of joint pain in children with
suggestions for investigations.

History taking

It is a widely believed aphorism that a physician should ‘listen to the patient and he or she will tell
you the diagnosis’ [18]. The history is the key for appropriate management of children with joint pains.
With the differentials in mind, a structured history will normally point to one or a few diagnoses, which
can be confirmed on examination or simple investigations. The history of the presenting complaint
890 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906

Table 1
Differential diagnosis of joint pains in children using a ‘surgical sieve’ approach [3,8,12e15].

Traumatic Fractures
Soft tissue injury
Non-accidental injury (NAI)
Overuse injury

Orthopaedic/mechanical Hypermobility-associated pain

Slipped upper femoral epiphysis (SUFE)
Perthes' disease
Developmental dysplasia of the hip (DDH)
Osteochondroses, for example, OsgoodeSchlatter disease (tibial tuberosity),
Sinding-Larsen syndrome (inferior patella), Kohler disease (navicular)
Osteochondritis dissecans
Scheuermann's disease
Spondylolisthesis
Leg length discrepancy
Club foot

Infectious Septic arthritis

Osteomyelitis
Discitis
Soft tissue infections
Psoas abscess
Lyme disease

Inflammatory Transient synovitis of the hip

Juvenile idiopathic arthritis (JIA)
Reactive arthritis
Acute rheumatic fever (ARF)
Chronic recurrent multifocal osteomyelitis (CRMO)/non-bacterial osteitis (NBO)
Systemic lupus erythematosus (SLE)
Juvenile dermatomyositis (JDM)
Vasculitis, for example, HenocheSchonlein purpura (HSP)
Mixed connective tissue disease (MCTD)

Neoplasia e benign Osteoid osteoma

Bone cyst
Chondroblastoma
Osteoblastoma

Neoplasia e malignant Leukaemia

Lymphoma
Neuroblastoma
Ewing's sarcoma
Osteosarcoma
Langerhans cell histiocytosis (LCH)

Idiopathic pain syndromes Growing pains/benign nocturnal limb pains (BNLP) of childhood
Diffuse idiopathic pain syndromes (juvenile fibromyalgia)
Complex regional pain syndromes (CRPS)

Other Haemophilia/haemarthrosis
Rickets
Osteonecrosis e sickle cell disease

Fabricated or induced illness

focusses on the pain, eliciting features summarised in the acronym SOCRATES (site, onset, character,
radiation, associated symptoms, time course, exacerbating/relieving factors and severity). Young
children are often unable to localise pain accurately, and it may not manifest in the typical way with
complaints of ‘it hurts’. Limp, reluctance to weight-bear or apparent regression of skills, for example, a
toddler who returns to crawling or wanting to be carried, may all be presentations of MSK pain.
When considering site and radiation, pain in a single focal area versus bilateral symmetrical versus
generalised can help narrow the differentials (see Table 2). Practitioners must beware of referred pain,
for example, a patient complaining of knee pain but with underlying hip pathology, in order for
 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906 891

Table 2
Aetiology of joint pains in children according to patient age and distribution of pain [14e16].

Age Localised pain Diffuse/multifocal pain

Under 3 years Toddler's fracture

Developmental dysplasia of the hip
Transient synovitis
3e10 years Transient synovitis Hypermobility-associated pain
Perthes' disease
Growing pains/BNLP
11e18 years Slipped upper femoral epiphysis Hypermobility-associated pain
Non-articular osteochondroses (OsgoodeSchlatter Diffuse idiopathic pain syndromes
disease, Sinding-Larsen syndrome)
Complex regional pain syndrome (CRPS)
All ages Trauma Polyarticular JIA
Non-accidental injury Leukaemia
Oligoarticular JIA Neuroblastoma
Infection (osteomyelitis, septic arthritis)
Malignancy (bone and soft tissue tumours)

BNLP, benign nocturnal limb pain; JIA, juvenile idiopathic arthritis.

Note that these represent the most common patterns but exceptions do occur (e.g., localised pain in leukaemia and CRPS
affecting children under 10 years).

conditions such as SUFE not to be missed [19]. Regarding the onset of pain, a clear history of acute
injury will often give the diagnosis; however, in the context of a more chronic course, the history of
trauma may be incidental to the actual diagnosis of inflammatory arthritis or malignancy [15].
A key dichotomy for primary care physicians to appreciate is the distinction between inflammatory
and non-inflammatory joint pains, which helps with decisions regarding investigation and referral.
Joint pain and stiffness, which is worse on rising in the morning and after periods of sitting, and eases
with activity, particularly when associated with persistent joint swelling, are indicative of an inflam-
matory aetiology [20]. Pain that is worse during activity and improves on rest suggests a non-
inflammatory cause. However, the latter can be associated with mild temporary joint swelling and
aching the morning after an active day; therefore, distinguishing inflammatory from non-
inflammatory causes is not always straightforward. One study has highlighted that isolated MSK
pain in the absence of other symptoms is very unlikely to be the presenting complaint of juvenile
idiopathic arthritis (JIA) or other chronic inflammatory disease [21]. Of 111 patients with isolated MSK
pain, only one had a rheumatological condition whereas 64 (84%) of 76 children ultimately diagnosed
with JIA did not include pain at all in the presenting symptoms.
A primary care assessment of joint pain should have a high sensitivity for detection of conditions
with the risk of mortality or long-term morbidity so that appropriate referral to secondary care can be
expedited. Table 3 summarises features (‘red flags’) in the history that can be used to distinguish
benign from potentially serious conditions, although there can always be exceptions [15]. Whenever a
child is assessed, the possibility of non-accidental injury must be considered. Key features include
delay in presentation; absence of, or variation in, the history to explain the injury; a mechanism
incompatible with the child's developmental age; and frequent injury or bruising of different ages [22].
The past medical history may highlight a preceding upper respiratory tract infection, which can
trigger a transient synovitis of the hip in a toddler or a sore throat, and genitourinary or gastrointestinal
infection, which may predate reactive arthritis [12]. Caution is warranted, however, given the effect of
recall bias and the high prevalence of viral infections in the childhood population, indicating that such
reports may be incidental [17]. A prolonged course of systemic corticosteroids in the drug history can
predispose to osteoporosis and an increased risk of fracture. A family history is important, particularly
of inflammatory or autoimmune conditions such as psoriasis, spondyloarthropathy, inflammatory
bowel disease and other HLA-B27-associated diseases. The psychosocial history aids understanding of
the impact of the pain on the child's life and the family's coping strategies [3]. Particularly in cases of
chronic non-inflammatory pain and complex regional pain syndrome, maladaptive family responses
may exacerbate and perpetuate the pain [16]. Details of travel and infectious contacts may raise the
suspicion of Lyme disease arthritis or tuberculous arthritis.
892 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906

MSK examination in children

Research has shown that confidence in MSK examination in children is low among both general
practitioners and paediatricians [23,24]. The skills have not been routinely taught to medical students
or paediatricians in training [25]; however, increasing numbers of medical schools are including
paediatric MSK assessment in their curricula [17]. Since 2012, the clinical examination of the Mem-
bership of the Royal College of Paediatrics and Child Health (MRCPCH) in the UK has included an MSK
station. Examination, investigation and management of MSK pathology also form a part of the Diploma
of Child Health (DCH) clinical examination syllabus. The DCH examination is taken by around 500
candidates each year, and it is aimed at primary care physicians and doctors who work in specialities
with frequent exposure to paediatrics (RCPCH data).
As discussed previously, joint pains may be the presenting feature of diseases that originate outside
the MSK system, such as leukaemia, or part of multisystem diseases such as systemic juvenile idio-
pathic arthritis (sJIA) or systemic lupus erythematosus (SLE). A full systemic examination should
therefore be considered, particularly in those with ‘red flags’ for serious or systemic disease in the
history. This would include assessing the skin for pallor, rashes or bruising, lymphadenopathy, hep-
atosplenomegaly and neurological examination, including muscle bulk and strength. Characteristic
rashes associated with MSK pains include the following: Gottron papules and heliotrope rash in der-
matomyositis, salmon-pink macules in sJIA, malar rash and photosensitivity in SLE, palmoplantar
pustulosis in chronic recurrent multifocal osteomyelitis (CRMO) and cafe
-au-lait spots in McCune-
eAlbright syndrome [8].
A simple and quick screening examination of the MSK system in children based on the adult Gait,
Arms, Legs and Spine (GALS) has been developed, and it is called paediatric GALS (pGALS) [26,27]. This
is increasingly being taught at medical schools, and it has been shown to be practicable and accepted by
families in developed and developing countries [28,29]. It is recommended as the initial assessment in
any child with MSK symptoms in the history; children who are unwell with pyrexia, with delay or
regression of motor milestones, and are ‘clumsy’ in the absence of neurological disease; and those with
a chronic disease with known association with MSK presentations [27]. A video of the full examination
is available to view on the Arthritis Research UK website [30]. Any area highlighted as abnormal by
pGALS should be examined in more detail using paediatric regional examination of the musculo-
skeletal system (pREMS) [31]. Several review articles provide detailed explanation of examination of
the back [32], hip [33], knee [34], foot and ankle [35]. Further practical guides are available on the
Paediatric Musculoskeletal Matters website [36].
The diagnosis of inflammatory arthritis can be made based on examination alone. Key features
include swelling of the joint with or without effusion, warmth, joint line tenderness, pain and/or re-
striction of movement, although not all may be present. Children often deny pain verbally when
examined; therefore, the physician should pay close attention to the child's face to detect grimaces and
note involuntary flinching when a joint is passively moved. Young people with hip inflammation often
localise pain to the groin, although it may be referred to the thigh or knee [33]. Arthritis tends to affect
certain movements before others, and the following features are most sensitive: loss of internal
rotation at the hip, hyperextension of the knee and extension of the cervical spine.

Investigations and referral

How long should I wait before investigating?

Following a complete history and examination, there are several management options depending
on the clinical findings:

1. Urgent or routine referral to secondary care without prior investigations

2. Investigations to confirm/refute diagnoses with the outcome determining referral or ongoing
management in primary care
3. Reassurance and follow-up in primary care without investigations
 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906 893

Fig. 1. Diagnostic approach to a child with joint pains [12,13,17]. Note that not all possible diagnoses are shown and that there are
always exceptions to the typical presentations of each disease. ASOT, anti-streptolysin O titre; CRP, C-reactive protein; CRPS, complex
regional pain syndrome; DDH, developmental dysplasia of the hip; ESR, erythrocyte sedimentation rate; FBC, full blood count; JIA,
juvenile idiopathic arthritis; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; sJIA, systemic juvenile idiopathic
arthritis; SLE, systemic lupus erythematosus; SUFE, slipped upper femoral epiphysis; US, ultrasound.
894 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906

Table 3
Features that help to distinguish benign from serious joint pains in children.

Benign features Serious features

History Pain worse on activity and
improves with rest
Pain worse at end of day
Symmetrical nocturnal pain
relieved by simple analgesia
and massage
No systemic symptoms
Pain or discomfort worse after rest and improved
with activity
Pain and stiffness worse in morning
Nocturnal pain not relieved by simple analgesia
and massage
Systemic symptoms e fever, night sweats, rash,
weight loss, malaise, easy bruising, anorexia

Examination No objective joint swelling Objective joint swelling

Hypermobile joints Restricted joints
No bony tenderness Bony tenderness
Normal muscle strength Muscle weakness
Normal growth pattern Poor growth, weight loss

Laboratory Normal FBC, ESR and CRP Abnormal FBC, raised ESR or CRP
investigations
Imaging Normal radiographic findings Abnormal radiographic findings: soft tissue swelling,
osteopenia, radiolucent metaphyseal lines, joint
space loss, effusion

CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FBC, full blood count.
Modified from Malleson and Beauchamp [15] with permission of the publisher.

One of the most important questions for practitioners to ask themselves before requesting an
investigation is ‘How would the outcome of this test alter my management?’ There are no evidence-
based guidelines on how long to wait before investigating a child with joint pains in primary care.
The majority of patients will not require tests because either urgent referral to secondary care is needed
or benign non-inflammatory causes can be determined from history and examination. Some in-
vestigations, such as routine blood tests and radiographs, are usually readily accessible to primary care
with results available within days. Therefore, they can be helpful with decision-making regarding
referral. Depending on the location of practice, other tests such as ultrasound, computed tomography
(CT) and magnetic resonance imaging (MRI) are associated with waiting times of weeks when
requested in primary care; therefore, referral to secondary care may be more appropriate where de-
cisions about further investigation can be made.

When should I refer and with what baseline investigations?

Clinical suspicion of the following diagnoses warrant referral to secondary paediatric care (pae-
diatric emergency department or orthopaedics) on the same day without delay incurred by per-
forming investigations in primary care: septic arthritis, osteomyelitis, fractures, non-accidental injury
and SUFE. In view of the potentially serious consequences of missing any of these diagnoses, a low
threshold for referral is recommended. Further details about the investigation and management of
some of these conditions are discussed later in the article. If malignancy is considered possible,
discussion with secondary paediatric care and subsequently paediatric oncology/haematology should
take place the same day with a view to arranging admission for investigation. These would include
bone marrow aspiration for haematological malignancy and CT or MRI for bone and soft tissue
tumours.
If clinical assessment suggests an inflammatory condition and the child is systemically well, referral
to paediatric rheumatology is most appropriate with outpatient review within 1e2 weeks. Table 4 lists
screening questions that may help to prompt appropriate referral [37]. JIA is a common cause for
arthritis in children (prevalence one in 1000), and it is diagnosed clinically as discussed in detail later.
Although the classification criteria for JIA specify the persistence of joint inflammation for at least 6
weeks [38], in order to avoid undue delay, it is reasonable for referral from primary care to paediatric
 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906 895

Table 4
Screening questionnaire for referral to paediatric rheumatology.

Screening questions

1 Have you noticed swollen joints in your child for the last 7 days?
2 Has your child complained of pain in the joints, muscles or bones for the last 7 days (not related to trauma)?
3 Has your child ever presented any swelling of the joints that lasted >30 days?
4 Has your child ever presented pain in the joints that lasted >30 days (not related to trauma)?
5 Has your child ever presented difficulties in closing the hands, folding the wrists, knees or ankles?
6 Has your child limped or walked in a different way in the last month?
7 Is there anything that your child cannot do, like playing or running, because he/she has presented any problems
in the joints?
8 Has your child ever woken up complaining of his/her joints?
9 Has your child ever had to cancel any everyday activity, like going to school or playing, because of pain in the
joints?
10 Does your child present any deformity in any joint?
11 Has your child ever had fever for >30 days without any apparent cause, followed by swelling or pain in the
joints?
12 Has your child ever presented any redness in the body followed by swelling or pain in the joints?

Score 1 for ‘Yes’, 0 for ‘No’ or ‘Don't know’. Final score ¼ sum of all answers (range 0e12). Children with a score  5 should be
referred to a paediatric rheumatologist.
Adapted from Len et al. [37] with permission of the publisher.

rheumatology to be made after 3e4 weeks of symptoms or signs. The British Society for Paediatric and
Adolescent Rheumatology have written Standards of Care for JIA, which recommend review by the
paediatric rheumatology team of all children and young people with suspected JIA within 10 weeks of
onset of symptoms and 4 weeks of referral [39].
Many causes of joint pains can be safely managed in primary care without the need for paediatric
referral. Growing pains, or benign nocturnal limb pain, affecting the typical ages of children with
‘classic’ symptoms do not require investigation, and they may be managed with reassurance, massage
and simple analgesia. Soft tissue and overuse injuries require rest, temporary modification of activities
and short-term analgesia. After excluding genetic conditions such as EhlerseDanlos syndrome, Mar-
fan's and osteogenesis imperfecta, patients with MSK pains associated with hypermobility benefit from
experienced physiotherapy assessment [40].

What laboratory investigations assist in diagnosis, classification and prognosis?

After consideration of the history and examination, there are likely to be a comparatively small
number of children presenting with joint pains in primary care who warrant laboratory investigations.
Trauma and non-inflammatory mechanical pains can usually be diagnosed clinically. Investigations aid
in inclusion or exclusion of malignancy, infections and inflammatory diseases. Table 5 summarises the
tests that can assist with differential diagnosis in primary care and those usually undertaken in sec-
ondary care for classification and prognosis. Antinuclear antibodies (ANAs), rheumatoid factor and
anti-double stranded DNA (dsDNA) antibodies are not useful as a ‘screen for rheumatological disease’,
and they should be reserved until after a clinical diagnosis is made or there is a high pretest probability
of autoimmune disease [15,41,42]. All tests have a false-negative rate and some diseases evolve over
time; therefore, if there is ongoing concern by the patient, family or physician despite negative in-
vestigations, planned review in primary care with repeat testing or referral to secondary care would be
advised.
A full blood count, blood film, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) can
be helpful in the diagnosis of joint pains. Although abnormalities are non-specific, if all parameters are
completely normal, the probability of a bone or joint infection, malignancy or inflammatory condition
is reduced but not zero [43,51,53]. The potential value of lactate dehydrogenase (LDH) in distinguishing
malignancy from JIA has been reported [65]. The retrospective study compared 12 patients with
neoplasia presenting with MSK symptoms, normal blood count and film to 24 patients with a final
diagnosis of JIA (20 sJIA, three polyarticular JIA and one oligoarticular JIA). The LDH was significantly
Table 5

896
Selected laboratory investigations for assessment of joint pains in children.

Test Indications Conditions associated with positive or Comments

abnormal results

FBC, differential Suspected malignancy, infection or Malignancy e cytopenias, may see blasts on WBC count not sensitive or specific for
and blood film inflammatory conditions film [43] malignancy, infection or inflammation.
Infection e increased WBCs and platelets May be normal in leukaemia [45,46].
Inflammatory e increased WBCs and platelets, FBC may be completely normal in

E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906
sometimes anaemia malignancy [47]
SLE e cytopenias [44]
ESR Suspected malignancy, infection or May be elevated in sJIA, polyarticular JIA, SLE, Sensitive but not specific [48] Elevated
inflammatory conditions malignancy ESR with low platelets concerning for
malignancy [43]
May be normal in JIA [49]. In
oligoarticular JIA, higher ESR at onset
associated with more severe disease
course [50].
CRP Suspected malignancy, infection or May be increased in malignancy, infection or Single measurement not sensitive or
inflammatory conditions inflammation. specific enough to identify all children
with serious infection [51]. Changes
more quickly in response to
inflammation than ESR [52]. If
CRP < 1 mg/dL, probability that patient
does not have septic arthritis is 87%
[53].
LDH Suspected malignancy or inflammatory May be elevated in malignant disease, such as LDH may be elevated in malignancy
condition leukaemia, and JDM even with normal FBC [45].
If JDM suspected, also measure CK, ALT
and AST [15].
ASOT Clinical suspicion of ARF or PSRA ARF, PSRA Fourfold rise in titre between tests 10
e14 days apart indicative of preceding
GAS infection: one of the criteria
necessary for diagnosis of ARF or PSRA.
Use in combination with anti-DNase B
[54].
Anti-DNase B Clinical suspicion of ARF or PSRA ARF, PSRA Use in combination with ASOT to
diagnose preceding GAS infection [54].
Throat culture Clinical suspicion of ARF Positive culture for GAS is one criterion for Growth of GAS may represent carriage
diagnosis of ARF rather than infection e risk of false
positives. High false-negative rate:
positive in only 10e33% of patients
with ARF [55].
 Urinalysis
Lyme titre
ANA
Rheumatoid factor
Anti-CCP antibodies
Anti-dsDNA antibodies
HLA-B27 genotype
Synovial fluid analysis
Synovial fluid culture
ALT, alanine aminotransferase; ANA, anti-nuclear antibody; AST, aspartate aminotransferase; ARF, acute rheumatic fever; ASOT, anti-streptolysin O titre; CCP, cyclic citrullinated peptide;
CK, creatine kinase; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; ERA, enthesitis-related arthritis; ESR, erythrocyte sedimentation rate; FBC, full blood count; GAS,
group A streptococcus; JIA, juvenile idiopathic arthritis; JDM, juvenile dermatomyositis; LDH, lactate dehydrogenase; PSRA, post-streptococcal reactive arthritis; sJIA, systemic juvenile
idiopathic arthritis; SLE, systemic lupus erythematosus; WBC, white blood cell.
Suspected systemic disease
Arthritis in child returning from Lyme disease-
endemic area
Not recommended in primary care e do not use
as ‘rheumatic disease screen’
Not recommended in primary care e do not use
as ‘rheumatic disease screen’
Not recommended in primary care
Not recommended in primary care
Not recommended in primary care. Used in
classification after diagnosis of JIA
To diagnose or exclude septic arthritis
To diagnose or exclude septic arthritis
Proteinuria and/or haematuria seen in SLE or
vasculitis
Elevated titre is evidence of current or prior
infection with Borrelia
Increased titre in some patients with JIA and
most patients with SLE
Increased titre in RF-positive polyarticular JIA
May be positive in some patients with
polyarticular JIA
Elevated in some patients with SLE
May be positive in enthesitis-related arthritis
(ERA) subtype. Associated with psoriasis,
inflammatory bowel disease and
spondyloarthropathy.
Septic arthritis: turbid fluid, WBC 50,000
e100,000/mm3, neutrophils >75% [62].
Transient synovitis: clear yellow, WBC 5000
e15,000 mm3, neutrophils <25% [62].
Normal: WBC <100/mm3
Positive in septic arthritis
Testing should be by indirect
immunofluorescence and not ELISA
[42]. High false-positive rate: 10e40%
in healthy children [41,42,56] In JIA:
sensitivity 57%, specificity 39%. In SLE:
E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906
sensitivity 93e95%, specificity 57% [57].
In context of JIA, ANA positivity
associated with increased risk of uveitis
[58]
Used for classification, not diagnosis, of
JIA. Positive in 5e10% of JIA patients
[52].
Role of anti-CCP antibodies in JIA
controversial [52]. May be associated
with increased risk of joint damage
[59,60].
In juvenile SLE: sensitivity 54%,
specificity 84e95% [52]. Titre used
clinically for monitoring disease
activity.
HLA-B27 positivity: 76% in ERA, 10% in
general population [61].
No growth in 20e50% of cases with
septic arthritis [63]. In many cases,
cause may be Kingella kingae, which is
difficult to culture [64].
897
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higher at 2.2 times the upper limit of normal (ULN) in the cancer patients compared with 0.8 times in
JIA. There was overlap in the distribution of LDH values in the two groups, but no patients with JIA had a
value greater than twice the ULN. The authors suggest that an elevated LDH in a child with joint pains
warrants a more thorough investigation for malignancy. The potential role of a high LDH suggesting
malignancy is supported by another retrospective caseecontrol study including 134 children with
malignancy (75% with acute lymphoblastic leukaemia (ALL)) or arthritis (50% oligoarticular, 25% sys-
temic and 21% polyarticular) [66]. The combination of high LDH with low neutrophil count and low
haemoglobin was associated most strongly with cancer. There have been no prospective studies of the
use of LDH (alone or in combination) or comparison with patient groups with joint pain other than
arthritis.

What diagnostic imaging assists in diagnosis?

A range of imaging modalities is helpful in diagnosing a child with joint pains and is detailed in
Table 6. Many are not easily accessible in primary care such as MRI or bone scans. In certain scenarios
where a diagnosis is suspected on clinical assessment, such as septic arthritis, the need for urgent
referral to secondary care takes priority over investigation in primary care, which may delay definitive
management.
A common presentation where imaging is helpful is the child with hip pain. If the history and
examination raise the possibility of Perthes' disease or SUFE, plain radiography can confirm the
diagnosis. The usual practice is to obtain both anteroposterior (AP) and frog-leg lateral (FL) views, the
latter being essential because of increased sensitivity of detection of an early slip in SUFE [14]. One
study has suggested that the FL view alone may be sufficient [78]. The solitary FL hip radiographs of 524
children with known diagnoses were reviewed by radiologists blinded to the AP view. There was a very
high agreement between assessments of the solitary FL versus the two views with a kappa of 0.989. In
view of this, the authors suggest the FL view alone is adequate to make a diagnosis while also reducing
radiation exposure and costs.
Plain radiographs are not helpful in excluding leukaemia, septic arthritis or inflammatory arthritis
as they can be normal in these conditions [3]. Ultrasound has a high sensitivity for the detection of
effusion in the hip joint, and it can be used as a first-line investigation for diagnosing, or excluding,
arthritis [13]. One study has suggested that in the absence of trauma and clinical risk factors for SUFE
(age > 10 years or obesity), ultrasound should be the initial investigation of choice for children with
hip pain [79]. In a prospective cohort of 55 children referred to hospital with hip pain and no clear
history of injury or known prior hip problem, 22 had plain hip radiographs arranged by primary care
(18 were AP views only) and all were normal. All 55 had bilateral hip ultrasounds, 48 of whom
showed effusion in the symptomatic hip. Seven were suspected to have septic arthritis based on
history and examination, and therefore they underwent joint aspiration and intravenous adminis-
tration of antibiotics, although the synovial fluid subsequently showed no microbial evidence of
infection. The final diagnosis in 45 patients with initial effusion was transient synovitis. Of four pa-
tients with persisting effusion at 26 days, two had Perthes' disease and one JIA. Given the utility of
ultrasound assessment for hip pain in children, a group in the emergency department of a children's
hospital trained emergency physicians to perform bedside ultrasound [80]. In symptomatic hips,
there was a sensitivity of 85% and a specificity of 93% for detection of an effusion, increasing in those
scans where physician self-rated confidence was high. While bedside ultrasound can streamline the
diagnostic pathway, it is likely practicable only in children's emergency departments because the
small numbers of children with hip pain per primary care physician would not warrant the cost of
equipment and time maintaining skills.

Important causes of joint pains in children

In the previous sections, we have discussed the diagnostic approach to joint pains in children,
highlighting the relative importance of the history and examination. Here, we present a more
detailed description of the investigation and referral pathways for a selected group of important
diseases.
Table 6
Diagnostic imaging for assessment of joint pains in children.
Test Indications
Plain Following trauma with suspicion
radiography of fracture, any significant joint
or bone pain or localised tenderness
Ultrasound To identify joint effusion
CT Second-line investigation for
complex fractures or bone tumours
MRI First line to investigate SIJs and
TMJs. Second line if plain radiograph
or US non-diagnostic
Bone scan Poorly localised MSK pains where
plain radiography or US inconclusive.
Multifocal disease or malignancy
Echocardiography Patients with fever, rash and arthritis
with possible ARF.
Suspected multisystem autoimmune
disease
ARF, acute rheumatic fever; CRMO, chronic recurrent multifocal osteomyelitis; CT, computed tomography; JIA, juvenile idiopathic arthritis; MRI, magnetic resonance imaging; MSK,
musculoskeletal; SIJ, sacroiliac joint; sJIA, systemic juvenile idiopathic arthritis; SLE, systemic lupus erythematosus; SUFE, slipped upper femoral epiphysis; TMJ, temporomandibular joint;
US, ultrasound.
E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906
Conditions associated with positive or abnormal results Comments
Fracture Imaging in two orthogonal planes. Always
SUFE include frog-leg lateral view of hip.
Perthes' disease Most children with leukaemia and lymphoma
Bone tumour have normal radiographs [45,46,67].
Chronic osteomyelitis
Septic arthritis First-line modality to assess soft tissue and joint
Inflammatory arthritis abnormalities. Unable to distinguish accurately
infective, inflammatory and haemorrhagic
effusion [68].
Fracture Limited utility in children because risks of
Bone tumours, including osteoid osteoma ionising radiation [14].
JIA e confirmation of arthritis in joints difficult to Higher sensitivity and specificity than plain
assess clinically or with US [69e71] radiographs or US [14].
Septic arthritis and osteomyelitis [72,73] Use of gadolinium enhancement increases
Bone and soft tissue tumours sensitivity for detection of inflammation.
Early Perthes' [74] Whole-body MRI has increasing role in
CRMO diagnosis of CRMO [75,76]. Younger children
may require general anaesthetic
Osteomyelitis [14,77] High sensitivity but lacks specificity [13].
Metastatic tumours
Occult fractures
Carditis in ARF. Pericarditis in SLE. Pericardial
fluid in sJIA
899
900 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906

Juvenile idiopathic arthritis

JIA is a clinical diagnosis that can be made in a patient with joint inflammation (arthritis) persisting
for 6 weeks with onset before 16 years of age (juvenile) where other causes have been excluded
(idiopathic) [38]. Joint pain can be a significant feature, although it often does not predominate in
comparison with non-inflammatory joint conditions [21]. Joint pain may be subtle, particularly in
younger children, and it can present as developmental delay or regression, distress during nappy
changes or a recurrent need for the child to be carried. Swelling, warmth and loss of function, including
limping if the lower limb joints are involved, are characteristic. Parents and children typically report
morning stiffness, and there may be a family history of autoimmune disease. It is increasingly
becoming clear that JIA does not represent a single disease, and systemic JIA in particular is generally
considered to be an autoinflammatory, rather than autoimmune, condition. Investigations are not
required to make a diagnosis of JIA. They are, however, useful for three main reasons:

1. To exclude another diagnosis

2. To provide support to a clinical diagnosis of JIA
3. To allow classification of JIA

First-line blood tests in suspected JIA would include full blood count with blood film, urea and
electrolytes, liver function tests, inflammatory markers and an autoantibody screen. Plain radiographs
are of little benefit in the diagnosis of JIA, except to exclude alternative pathology. Whilst a diagnosis of
JIA cannot be made before 6 weeks of symptoms, all children with suspected JIA should be referred to a
paediatric rheumatologist for further assessment. Referral should be made without delay in suspected
JIA; a retrospective cohort study of 128 children treated with methotrexate, a commonly used agent in
JIA, showed that time from diagnosis to initiation of methotrexate was an important factor in response
to treatment [81]. Whilst the blood tests listed earlier are useful in diagnosing JIA and subtyping the
disease, normal blood test results do not preclude a diagnosis of JIA and should not prevent referral to a
paediatric rheumatologist. In addition, more specialist autoimmune blood tests need to be interpreted
in the context of the child; a large meta-analysis of the performance of ANAs, rheumatoid factor and
anti-cyclic citrullinated peptide antibodies was unable to support the use of these tests as diagnostic
tests for children with undiagnosed MSK pain [82]. Initial management of children with JIA is multi-
faceted comprising physiotherapy, occupational therapy and medication (including analgesic and anti-
inflammatory or immunosuppressive treatment). The prognosis of JIA varies greatly between the
different subtypes of the condition, with oligoarticular JIA having the best prognosis [83]. A large
systematic review published recently aimed to identify early predictors of prognosis in JIA in terms of
disease activity, joint damage, function and quality of life. The study found that demographic, clinical
and laboratory values were not sufficient early predictors of long-term outcome, and very few studies
exist to look at genetic or immunological predictors of prognosis [84].

Septic arthritis

The history of septic arthritis is often one of acute-onset, severe joint pain, usually affecting a single
joint. The pain is often so severe as to cause night waking. The hips and knees are common sites of
septic arthritis, although it is possible for any joint to be involved. Classically, the child will be febrile
and reluctant to weight-bear or move the joint, although signs and symptoms are often more subtle in
younger children. On closer inspection, the joint is usually red, hot, swollen and markedly tender [85].
There are significant numbers of children in the community who are immunosuppressed, due to either
medication or concurrent illnesses, and these children require a higher level of suspicion. Kocher et al.
described a prediction rule to help differentiate septic arthritis from transient synovitis. The criteria
consist of refusal to weight-bear, white cell count >12  109/L, ESR >40 mm/h and fever >38.5  C. The
probability of septic arthritis depends on the number of criteria fulfilled: 0.2% with zero criteria pos-
itive, 3% if one criterion positive, 40% if two criteria positive, 96% if three criteria positive and 99% if all
four criteria are met [86].
 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906 901

In an otherwise well and afebrile child, it would be reasonable to take blood tests for white cell
count, CRP and ESR if results can be obtained urgently. In children meeting none or one of the Kocher
criteria, the child could be reviewed in 24e48 h with appropriate safety netting. However, any child
with a strong suspicion of a septic joint or meeting two or more of the Kocher criteria should be
referred to secondary care for further investigation, due to potentially devastating acute and long-term
effects of an untreated septic joint. Blood cultures are useful in guiding therapy; however, <25% come
back positive [87] and some organisms such as Kingella kingae are felt to be underestimated using
traditional culture techniques [88]. Plain radiographs are of little value in suspected septic arthritis, as
they are often normal in the early stages. Ultrasound may be of benefit in identifying joint effusion, but
it will not differentiate an effusion in a septic joint from an inflammatory one. Management of septic
arthritis requires arthrotomy and antibiotics under the guidance of an orthopaedic surgeon.

Transient synovitis

Transient synovitis is a benign, self-limiting condition typically affecting children aged 3e8 years
[89]. It is one of the most common disorders of the MSK system in children [90]. Children present
without ‘red flag’ features, and they are usually able to weight-bear and have some hip joint move-
ment. Transient synovitis is a diagnosis of exclusion. The condition should begin to improve over
several days with full recovery within 2 weeks [91]; thus, treatment is with analgesia and rest. There
are no diagnostic tests for transient synovitis; thus, appropriate safety netting and clinical review are
necessary if symptoms persist, as Perthes' disease can present very similarly in the early stages.

Perthes' disease

Perthes' disease is a condition that affects children up to age 12 years due to idiopathic femoral
capital epiphyseal vascular compromise [92]. Boys are more commonly affected than girls, although the
exact aetiology and pathogenesis is unknown [93]. Perthes' disease usually presents as hip pain, or
referred knee pain, and a limp, without other systemic features. On examination, there is often loss of
internal rotation of the hip. Blood tests may be carried out to exclude other causes of hip/knee pain, but
these are usually normal in Perthes' disease. Definitive diagnosis is with radiographs, correlated with
clinical findings. Perthes' disease can closely mimic transient synovitis initially; thus, it is important
that all children with a ‘transient synovitis’ that is not improving undergo radiographic imaging of the
hips. Traditionally, AP and FL radiographs are used for diagnosis; however, more recent evidence
suggested FL radiographs are sufficient for diagnosis and also reduce radiation exposure [78].
Approaches to the treatment of Perthes' disease vary widely across centres [94], but they generally
aim to minimise pain, maximise joint mobility and prevent irreversible damage to the femoral head.
Damage to the femoral head as a result of untreated Perthes' can result in arthritis and the need for
subsequent hip replacement in early adulthood, hence the importance of imaging and orthopaedic
referral in cases of limp persisting over a period of weeks. Early diagnosis and surgery have been shown
to improve outcome in older children (over 6 years of age) with Perthes', whereas younger children
benefit from being managed non-surgically particularly if they present early [95].

Slipped upper femoral epiphysis

SUFE is a common cause of hip pain in adolescence [96]. Symptoms may be subtle with pain or
aching in the hip, thigh or knee [19]. Delay in stabilisation of the SUFE is associated with increasing slip
severity and adverse outcome such as avascular necrosis of the femoral head [97]; thus, an urgent
referral to an orthopaedic surgeon or emergency department should be made in cases of suspected
SUFE. In one study investigating delays in diagnosis, there was a notable delay in the time from onset of
symptoms to definitive diagnosis for those patients who presented to primary care rather than to an
emergency department, although the reasons for this were unclear and may be partially attributed to
different severity of symptoms between the two groups [98]. The outcome and prognosis of SUFE
depends on early detection and stabilisation of the hip; thus, primary care physicians should remain
alert to the possibility of SUFE in adolescent patients with hip, thigh or knee pain.
902 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906

Malignancy

Whilst malignancies, both haematological and solid tumour, are a rare cause of joint pain in chil-
dren, the devastating impact of a missed diagnosis makes malignancy an important differential cause
of joint pain in children [45,99,100]. Paediatric malignancies may present to a paediatric rheumatol-
ogist as suspected JIA. The use of steroids for presumed JIA in these children further complicates the
clinical picture, ultimately leading to a delay in correct diagnosis and management.
Leukaemia is the most common malignancy of childhood and can present as isolated pain in a single
joint, manifesting as a limp in up to 30% of cases [101]. Solid tumours such as Ewing's sarcoma, whilst
rarer, can also present with joint pain and fever [43]. Children with malignancy may have specific
features including haematological abnormalities (such as bleeding, bruising or pallor) or pain that is
unremitting and severe enough to cause night waking. However, many of the other signs and symp-
toms seen in children with malignancy share features with those associated with JIA: the children may
have systemic features such as weight loss, fever, malaise, lymphadenopathy or organomegaly. Chil-
dren with these features should be urgently assessed by a paediatrician as further investigation is likely
to involve more specialist tests. Investigations in these children include full blood count with blood
film, bone marrow aspiration and imaging. Three cases have recently been reported of children pre-
senting to the rheumatology clinic with joint pain who were subsequently found to have malignancy
on bone marrow examination and had normal blood counts on presentation [47]. Each child had ‘red-
flag’ features on history or examination. A retrospective analysis of 277 children attending one rheu-
matology clinic over 3 years, of whom 71 went on to have a diagnosis of ALL, examined the features
predicting a diagnosis of ALL. They found that a low WBC count (<4  109/L), low normal platelet count
(150e250  109/L) and nocturnal pain were the three most important factors in predicting a diagnosis
of ALL, with 100% sensitivity and 85% specificity if all three features were present [101]. These cases
illustrate both the importance of thorough clinical assessment and the need for cautious interpretation
of potentially falsely reassuring full blood counts and blood films in children with ‘red-flag’ features.
The prognosis of children with cancer who present with joint pain is beyond the scope of this review,
but it will ultimately depend on the type of malignancy.

Growing pains

Growing pains are commonly encountered in the period from childhood to puberty [102], although
the aetiology is unknown [103]. Whilst growing pains tend to affect whole limbs rather than joints,
their frequency and benign nature mean that it is important for clinicians to be confident in the
diagnosis of this condition. Peterson gave a definition of growing pains in 1986 [104], which was later
modified by Evans [105] and is useful in guiding clinicians (Table 7). The history tends to describe
intermittent, generalised, nocturnal leg pain in an otherwise-well child with normal examination.
There are no diagnostic tests for growing pains; despite this, children often undergo extensive

Table 7
Inclusion and exclusion criteria for growing pains [105].

Inclusion Exclusion

Nature of pain Intermittent Persistent

Some pain-free days Increasing intensity

Unilateral or bilateral Bilateral Unilateral

Location Anterior thigh, calf, posterior knee Joint pain
Onset of pain Late afternoon/evening Pain still present next morning

Physical examination Normal Swelling, erythema, tenderness

Local trauma or infection
Reduced joint range of movement
Limping

Laboratory tests Normal Objective findings (elevated ESR, abnormal

radiographs or bone scan)
 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906 903

investigations with up to 19% of children having bone scans [106]. No blood tests or imaging is required
if the history and examination is typical for growing pains, as evidenced in one caseecontrol study of
150 children with limb pain [107]. However, if there are any atypical features, other causes of MSK pain
should be investigated before a diagnosis of growing pains is made. The mainstay of management of
growing pains is reassurance, the use of hot or cold compresses, massage and simple analgesics as
needed [103].

Conclusion

Joint pains in children are a common presentation to primary care, and they may prove a diagnostic
challenge. In most cases, the cause is benign and symptoms resolve over a short time. Rarely, MSK pains
result from diseases with serious long-term morbidity and mortality. The key in primary care is to
consider the broad differential and use a careful history and examination to select those children who
require investigation and referral. The evidence and recommendations presented here should help
with that process.

Practice points

 A thorough musculoskeletal history from the family and, where possible, child is key to
diagnosis of children with joint pains
 Primary care physicians should be competent in performing and interpreting a musculo-
skeletal examination (pGALS) in children
 Awareness of the ‘red flags’ in history and examination help to select children appropriately
for further investigation and referral to secondary care
 Suspected septic arthritis, osteomyelitis, fractures, non-accidental injury and slipped upper
femoral epiphysis warrant urgent referral to secondary care without investigations that could
delay definitive treatment
 Juvenile idiopathic arthritis can be diagnosed clinically on history and examination, and
referral of suspected cases should be made to a paediatric rheumatologist without delay
 A ‘rheumatological disease screen’ is diagnostically unhelpful with a high frequency of false
positives and negatives, and it is not recommended in primary care

Research agenda

 Investigation of the factors contributing to delays between onset of symptoms and presen-
tation to secondary care of children with musculoskeletal symptoms with underlying ma-
lignancy, infection or inflammatory causes
 Development of further training to improve skills in MSK examination of children by primary
care, emergency physicians and paediatricians [17]
 Prospective studies to evaluate which combination of laboratory tests identifies children with
malignancy presenting with joint pains with the greatest sensitivity and specificity
 Prospective study of an imaging protocol for management of non-traumatic hip pain in
children [78]

Author contributions

E.S. Sen and S.L.N. Clarke performed a literature review and wrote the article. A.V. Ramanan made
contributions to discussion of content and review/editing of the manuscript before submission.
904 E.S. Sen et al. / Best Practice & Research Clinical Rheumatology 28 (2014) 888e906

Competing interests statement

E.S. Sen declares no competing interests.

S.L.N. Clarke declares no competing interests.
AVR has received honoraria/speaker's fees from Abbvie, Pfizer, Roche, Novartis and SOBI
Pharmaceuticals.

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