The hallmark of juvenile idiopathic arthritis is synovial inflammation, and the goal of treatment is to suppress inflammation to prevent cartilage damage and bone erosions. Ultrasound and MRI are widely used imaging modalities in evaluating disease burden and response to treatments and are superior to clinical examination alone. However, differentiating between the normal appearance of the developing skeleton and pathologic conditions can be difficult, particularly in early disease. Larger, long-term studies are needed to standardize imaging definitions and protocols and to fully understand the clinical implications of imaging findings.
Imaging is useful to evaluate the extent and severity of inflammation, degree of joint damage, and response to treatment in children with juvenile idiopathic arthritis.
Ultrasound scan demonstrates subclinical synovitis and enthesitis in children with juvenile idiopathic arthritis and is a useful adjunct to the clinical examination.
Conventional radiography has a limited role in the assessment of juvenile idiopathic arthritis and in established disease should only be used to evaluate those patients with change in symptoms or management.
MRI offers the most complete imaging analysis and provides assessment of the extent of synovitis, bone marrow and soft tissue edema and can reliably depict early erosive disease.
Interpretation of all imaging modalities is hindered because of gaps in knowledge regarding the normal appearance of the healthy growing skeleton, and more information is needed to produce validated scoring systems.
Juvenile Idiopathic Arthritis: Definition and Classification
Juvenile idiopathic arthritis (JIA) is an umbrella term that encompasses all forms of arthritis that begin before the age of 16 years, persist for more than 6 weeks, and are of unknown etiology. JIA is the most common childhood rheumatic entity, with a prevalence of 0.6 to 1.9 in 1000 children. The exact etiology is not fully understood but is thought to include both environmental and genetic factors. JIA encompasses a heterogeneous group of arthropathies that have been defined by the International League for Rheumatology ( Table 1 ).
|Category||Frequency (%)||Sex||Age at Onset||Definition|
|Systemic arthritis||4–17||F = M||Throughout childhood||One or more joints affected with or preceded by at least 2 wk of fevers that have been daily for at least 3 d, with at least 1 of the following: transitory rash, generalized lymphadenopathy, hepatomegaly or splenomegaly, or serositis|
|Oligoarthritis||27–56||F >>> M||Early childhood, peak 2–4 y||One to 4 joints affected within 6 mo of onset|
|Polyarthritis (RF negative)||11–28||F >> M||Early peak 2–4, late peak 6–12 y||Five or more joints affected within 6 mo of onset, with a negative RF test|
|Polyarthritis (RF positive)||2–7||F >> M||Late childhood–adolescence||Five or more joints affected within 6 mo of onset, with 2 positive RF test results at least 3 mo apart within 6 mo of disease onset|
|Psoriatic arthritis||2–11||F > M||Early peak 2–4, late peak 9–11 y||Arthritis and psoriasis, or arthritis and 2 or more of the following: dactylitis, nail pitting or onycholysis, or psoriasis in a first-degree relative|
|Enthesitis-related arthritis||3–11||M >> F||Late childhood–adolescence||Arthritis and enthesitis, or arthritis or enthesitis with 2 or more of the following: presence or history of sacroiliac joint tenderness or inflammatory low back pain; positive HLA-B27 antigen; male over 6 y at onset; acute (symptomatic) anterior uveitis; or a history of ankylosing spondylitis, ERA, sacroiliitis with IBD, Reiter syndrome, or acute anterior uveitis in a first-degree relative|
|Undifferentiated||11–21||Fits into none or at least 2 of the other categories|
The hallmark feature of all subtypes of JIA is joint inflammation. This typically begins as inflammation of the synovial lining, the thin layer of soft tissue that lines joint cavities, tendon sheaths, and bursae. If left untreated, synovial inflammation progresses to synovial hyperplasia with increased vascularity, resulting in a highly cellular inflammatory pannus. The pannus will eventually erode into the overlying cartilage and bone as a result of antibody deposition and degradative enzymes, leading to articular destruction. In children, inflammation may also cause growth disturbances, both systemically and locally in affected joints.
Juvenile Idiopathic Arthritis Imaging Principles
Imaging studies help identify children with a high likelihood of early erosive joint damage, providing an opportunity to implement aggressive therapy at an early stage in an attempt to reduce morbidity. Although the diagnosis is based on clinical and laboratory findings, imaging plays an important role for both the diagnosis and patient follow-up. Traditionally, imaging studies largely consisted of conventional radiographs. Plain radiographs have poor sensitivity in depicting active arthritis and rarely show erosive change until late in the disease course. The use of ultrasonography (US) and MRI to evaluate pediatric arthropathy has been steadily increasing, as these modalities can reliably assess abnormalities within the synovium, cartilage, and bone. As a result, the management of JIA has evolved to include greater use of cross-sectional imaging to detect inflammatory lesions before permanent joint destruction occurs, monitor disease progression and extent, assess treatment response to more effectively guide therapy, and evaluate complications associated with the disease or its therapy. Imaging can more accurately distinguish between arthritis and tenosynovitis than clinical examination alone and, in some cases, can help define the subtype of JIA.
Imaging children with inflammatory arthritis is challenging given the unique features of the growing skeleton and scarcity of normative data. To correctly diagnosis these conditions, one needs to be familiar with the normal age-dependent changes that occur during growth and development of the healthy skeleton. Physiologic features of recently ossified bones can be misinterpreted as cortical erosions, and the thickness and vascularity of epiphyseal cartilage varies with skeletal maturation. To date, there are no defined imaging protocol recommendations; thus, the timing and use of imaging in JIA is tailored to the individual patient. Established adult protocols and standardized scoring systems must be modified before they can be applied to pediatric patients. Much of the recent work has been established by task forces that combine collaboration with radiologists and clinical rheumatologists from large pediatric centers.
US is a dynamic, rapid and inexpensive method of evaluating patients with JIA. US allows for a survey of multiple joints without the need for sedation or exposure to radiation. US provides a reliable assessment of synovial proliferation, joint fluid, cartilage thickness, cartilage and cortical erosions, and tenosynovitis. In addition, US is used to guide joint aspiration or injection. The use of high-frequency (12–18 MHz) linear transducers allows for excellent resolution of joints and tendons in children. Color and power Doppler imaging can assess synovial vascularity and hyperemia. US contrast agents may further improve evaluation of synovial proliferation and hyperemia.
Young children can be challenging to image with US, as patient motion can cause artifact on grayscale imaging and prohibit reliable Doppler signal. Imaging in a child-friendly environment with warm jelly is advised, and it is often helpful to take the image while the child is seated or reclined in the lap of the parent. Distraction with videos/television or the use of Child Life Services can improve patient compliance for a more reliable examination. Stand-off pads and the water bath technique are also useful, especially when imaging small joints in very young children ( Fig. 1 ).
OMERACT 7 (Outcome Measures in Rheumatoid Arthritis Clinical Trials) special interest group established the following definitions of the US signs of inflammatory arthritis.
Synovial thickening and synovitis
Thickening of the synovium is seen as solid, noncompressible, abnormally hypoechoic tissue associated with joint lines or surrounding tendons. Assessment for synovial thickening may be more challenging in younger children, as synovial tissue may be difficult to discern from adjacent hypoechoic epiphyseal cartilage.
Synovial thickening might not necessarily reflect ongoing disease. Color and power Doppler US techniques are superior to gray-scale US in identifying active disease. Doppler US depicts synovial blood flow, suggesting increased synovial vascularization and synovitis ( Fig. 2 ). However, healthy children may exhibit some Doppler signal because of physiologically enhanced blood flow.
A joint effusion is depicted as abnormal hypoechoic or anechoic (relative to subdermal fat), or in some cases isoechoic or hyperechoic, intra-articular material that is displaceable and compressible but does not show Doppler signal. Physiologic fluid is common in children, and it can be difficult distinguishing between normal amounts of joint fluid from a joint effusions, as there are little data regarding the normal amount of synovial fluid in healthy children. Several studies evaluated the appearance of joint fluid on US in healthy children.
Tenosynovitis appears as hypoechoic or anechoic thickened tissue with or without fluid in the tendon sheath, which may exhibit Doppler signal. It is imperative that this abnormal finding is seen in 2 perpendicular planes to account for anisotropy, which may falsely depict hypoechogenicity within a tendon if the transducer is not placed 90° to the tendon ( Fig. 3 ). In children, tenosynovitis is most commonly seen around the ankle joint and along the extensor tendons of the wrist.
Inflammation at the tendinous or ligamentous insertion appears as an abnormally hypoechoic (loss of the expected fibrillary architecture) or thickened tendon or ligament at its bony attachment that is seen in 2 perpendicular planes. This image may contain foci of calcification and may exhibit abnormal Doppler signal or bony changes such as enthesophytes, erosions, or cortical irregularities; however, these features are less commonly seen in children.
A bone erosion is defined as discontinuity of the bone surface visible in 2 perpendicular planes. Assessment of erosive changes in children is challenging, as there are physiologic irregularities in recently ossified bone that can be misinterpreted as cortical erosions, highlighting the need for further knowledge of normal bone anatomy throughout pediatric age groups.
US can be used to evaluate the integrity of cartilage. Epiphyseal cartilage in very young children appears near anechoic and increases in echogenicity with maturation. It is imperative to recognize the relative hypoechogenicity of epiphyseal cartilage so that it is not incorrectly classified as joint fluid ( Figs. 4 and 5 ). The cartilage appearance changes in signal and thickness with advancing maturity, with boys exhibiting thicker cartilage than girls at a given age because of earlier maturation in girls. Articular cartilage is normally seen as a hypoechoic structure with a smooth outline, which overlies the bone surface. Early changes of cartilage erosion and thinning can be detected as blurring and obliteration of the normally sharp margins of the cartilage surface. Age- and sex-related normal reference standards for cartilage thickness of the knee, ankle, wrist, and metacarpophalangeal and proximal interphalangeal joints for children between the ages of 7 and 16 years have been established. This work was further evaluated by showing good agreement between MRI and US for the measurement of cartilage thickness in healthy children. Patients with JIA have shown reduced cartilage thickness when compared with age- and sex-matched controls, although interestingly, this finding is observed in both clinically affected and nonaffected joints. Recently, Roth and colleagues established definitions for the US appearance of joints in healthy children to determine a basis to better define these conditions and to further support the use of US in pediatric rheumatology.
Ultrasound Scoring Systems and Impact
There are no validated US scoring scales for evaluating JIA. A semiquantitative system for grading synovial thickening is used in adult rheumatology, but no such system has been validated in JIA.
US assessment of disease activity can be more informative than clinical examination. Subclinical synovitis is frequently observed by US, particularly within the hands and feet.
In addition to synovitis, US can detect subclinical enthesitis. Jousse-Joulin and colleagues found that Doppler US showed enthesitis in 50% of clinically normal entheses in patients with JIA. Of the healthy children evaluated, none had US evidence of enthesitis. Weiss and colleagues evaluated standard dolorimeter examination for the detection of enthesitis in children with enthesitis-related arthritis and found that dolorimeter testing had poor accuracy and reliability compared with power Doppler US.
The prognostic significance of subclinical information still needs to be determined. However, US is a powerful tool that may allow differentiation between synovial, tendinous, and entheseal inflammation. US may impact classification of a JIA patient, detecting asymptomatic joint involvement, which would reclassify a patient previously thought to have oligoarticular arthritis as having polyarticular arthritis. Active disease in at least 5 joints (polyarticular arthritis) would meet inclusion requirements in clinical trials of second-line or biological agents. Identification of subclinical disease may potentially alert the treating physician toward more aggressive treatment and close monitoring of the patient.
Ultrasonography is highly operator dependent, and the scarcity of data regarding standardized imaging protocols limit reproducibility, interpretation, and comparison of studies. US is unable to assess for bone marrow edema. In large joints, the adjacent bone limits visualization of the articular cartilage deep within the joint. Another limitation of US is its limited ability to assess difficult joints such as the temporomandibular joints and sacroiliac joints. It has been shown that US is not reliable in the assessment of active temporomandibular joint arthritis and that MRI should be performed. In addition, US has a high false-negative rate in evaluating active subtalar disease.
Conventional Radiograph Findings and Technique
Conventional radiography is traditionally the mainstay of imaging in JIA and plays an important role in the initial diagnosis by excluding other causes of joint pain and swelling. Radiographs are also useful for identifying late complications of JIA such as accelerated bone growth, premature physeal fusion, and limb length discrepancy. Radiographic findings in early-stage JIA are often nonspecific and include soft-tissue swelling, joint effusions, and demineralization. Both juxta-articular and generalized demineralization are common early findings on radiographs, reflecting localized hyperemia, trabecular atrophy, and reduced endochondral bone formation. As the disease progresses, localized hyperemia of the joint may result in epiphyseal enlargement, accelerated maturation, and osseous overgrowth. During early stages of the disease, accelerated growth results in a relative increased length of the affected limb; however, in long-standing disease, accelerated maturation leads to premature physeal fusion and resultant limb shortening or joint malalignment. Advanced findings include ankylosis and periarticular changes with muscular and ligamentous atrophy resulting in joint contractions ( Fig. 6 ).