Introduction
It can be difficult to assess the level of disease activity in children with juvenile idiopathic arthritis (JIA) based on clinical examination alone. Ultrasonography is an important outcome measure to enhance clinical assessment, and provides important information for diagnosis, treatment monitoring, and procedure guidance.
Detailed knowledge of the physiology of the pediatric joint is important to discriminate findings suggestive of pathology. With appropriate interpretation, ultrasonography can play an important role in treat-to-target (T2T) approaches, and may also support the interaction of healthcare providers with patients and parents.
Rationale for using ultrasonography in juvenile idiopathic arthritis: The “why?”
JIA is a potentially debilitating, chronic disease which affects children and adolescents of all ages, with an overall peak incidence around 2 years of age.
Treatment options have evolved dramatically over the past 2 decades, and it has become clear that appropriate guidance is necessary in order to apply these treatments optimally and improve outcomes. An extensive body of data in adults with rheumatoid arthritis has shown that a targeted treatment approach leads to improved outcomes, and this may also apply in other rheumatic diseases including JIA.
There are currently few studies in the context of JIA, but early data show that standardized disease activity assessments and a regular target review improve outcomes significantly. Traditionally the target has been clinically defined as remission or low disease activity. However, in the context of JIA, a clinical assessment may not be sufficient to define disease activity. Furthermore, taking a history and performing a physical exam may be challenging, especially in some younger patients.
As such, it is not surprising to see an increased interest in the addition of imaging methods in the management of JIA. Among the available methods, musculoskeletal ultrasonography (MSUS) and magnetic resonance imaging (MRI) are favorites given the lack of radiation exposure to patients and the ability to provide a complete assessment of synovitis, including structural parameters as well as measures of inflammation. MSUS has unique advantages, including the ability to assess several joints without sedation, even in young children, at point of care and at a much lower cost than MRI. A combination of brightness mode (B-mode) and Doppler ultrasonography may be best to assess structural changes as well as hyperemia associated with acute inflammation.
Musculoskeletal ultrasonography and subclinical disease activity
Several studies in JIA have shown that MSUS is more sensitive than clinical examination in the assessment of joint inflammation. All of these studies demonstrate discrepancies in the number of active joints between the clinical exam and ultrasonography. Overall, 30% of joints assessed as normal on physical exam show signs of synovitis on MSUS. Unfortunately, lack of a clear definition of synovitis and misinterpretation of low-grade, likely physiologic, Doppler signals might explain why in some of the existing literature subclinical ultrasound findings failed to predict disease flares. More recent studies with improved methodologies nevertheless show the importance of subclinical ultrasound findings in the prediction of flares.
Synovitis in children on musculoskeletal ultrasonography: How to discriminate pathologic from physiologic findings
Through various international consensus efforts, definitions for the components of the normal pediatric joint have been issued. These include:
- A clear description of the epiphyseal bone with the interruption of the bone contour at the growth plate.
- A variable amount of cartilage.
- The presence of hyperechoic signals within the cartilage that represent vascular channels as well as physiologic blood flow, detectable as Doppler signals that can be demonstrated in any part of the joint (see Figure 1).
Figure 1: Normal wrist joint showing features of pediatric anatomy. On the proximal end (left) an interruption of the bone (radius) can be seen, representing the growth plate. Blood flow can be seen in the intraarticular, extrasynovial area. Ossification is incomplete; especially of the lunate bone, which shows an anechoic halo around it.
Abbreviations: MC, metacarpal bone.
Defining synovitis on ultrasonography
As in adults, the assessment of synovitis by ultrasound in children requires the use of both B-mode and Doppler mode, and an international consensus on the definition of sonographic features of synovitis in children has been published. This definition stresses the need to clearly identify the synovial recess on B-mode and differentiate this recess from other connective tissue, which may be intraarticular but extrasynovial. Only Doppler signals within an area of synovial hypertrophy are clearly suggestive of increased blood flow as part of the inflammatory process. This clear emphasis on the precise intrasynovial, and not just intraarticular, location of the Doppler signals represents an evolution of the existing definition in adults. An example of synovitis is shown in Figure 2.
Figure 2: Synovitis of the elbow joint. Posterior longitudinal view of the elbow joint with intraarticular hyperechoic fat (bright) and synovial proliferation and fluid (hypo- to anechoic). Doppler signals can be seen in an intraarticular but extrasynovial location and also in a true intrasynovial location.
Assessing damage
Chronic synovitis may cause significant damage to cartilage and bone. The consequence of functional impairment may be especially problematic in children as they have a long life expectancy ahead of them. MSUS is able to assess damage to cartilage and bone reliably in most joints, although MRI, but not radiographs, may be superior in some locations. It is also important to note that the focus on cartilage and bone may be driven by the use of radiographs as traditional means of assessing damage.
From a functional point of view, damage to soft tissue structures may be even more important. This includes tendon tears, ligament lesions, and lesions to other structures supporting the normal function of the musculoskeletal system. One example would be the damage to pulleys keeping the flexor tendons of the fingers in place, which may become compromised secondary to chronic inflammation, with a lack of proper guidance of the tendon as a result.
Musculoskeletal ultrasonography as a tool to monitor JIA
When trying to use MSUS as a tool to monitor JIA, one essential question is: how many joints should be assessed, and at which time points? The literature does not give clear answers, but it might be reasonable to assume that MSUS can be a useful adjunct to clinical assessment at any major decision point, including diagnosis, remission, flare, change of treatment, and the planning of a joint injection. Suggestions for a minimum number of joints to assess and first semiquantitative scores have been published.
Other roles of musculoskeletal ultrasonography in a treat-to-target approach of JIA
MSUS may contribute to the management of JIA by supporting early diagnosis (an essential step for implementation of T2T) and by capturing the full picture of pathology in many areas of the joint, entheses, and tendons. Many joints are complex and require the assessment of multiple synovial recesses, tendon sheaths, the paratenon, and entheses.
MSUS is important in the precise planning of joint injections and increases options even in difficult locations. Joint injections can be an important adjunct as part of a T2T approach in patients already on systemic therapies with an incomplete response. They are also an important treatment options for patients who may not have full access to all treatment options, either because of their geographic location or limitations in medication coverage.
Finally, MSUS allows the inclusion of patients and parents in the decision-making process through the visual illustration of inflammation and other aspects, something that can be difficult for patients and parents to understand, especially in the absence of symptoms. In the latter scenario of discordance between the patient’s symptoms and the physician’s clinical assessment, MSUS may enhance compliance with treatment.
Conclusion
In summary, MSUS is an important measurement tool in the care of children with JIA as part of a T2T approach. It helps to determine relevant subclinical disease activity and is applicable for most joints. When embedded in the overall clinical assessment, it is well tolerated and has benefits on many levels.