For patients with juvenile idiopathic arthritis (JIA), musculoskeletal ultrasonography (MSUS) vs other imaging modalities offers significant benefits, including safety, noninvasiveness, repeatability, rapid performance, relatively low cost, and high acceptability even among very young patients. In addition, MSUS can detect subclinical synovitis, improve the classification of subtypes, and capture early articular damage, as well as help clinicians monitor treatment response and guide intra-articular injections.1 Moreover, across a majority of studies, many researchers have agreed that MSUS is superior to clinical examination in detecting synovial hypertrophy and synovial effusion.2

However, a recent viewpoint article published in the Annals of the Rheumatic Diseases argued that MSUS has a high probability of identifying routine features of a growing skeleton as pathologic. Researchers of this report concluded with a call for better training in physical examination, which should be preferred to MSUS in assessing joint abnormalities in JIA.3

Is MSUS a Reliable Imaging Tool in JIA?

An argument made by the investigators against using MSUS was partially countered by other researchers collecting data on pediatric joint development, as well as by the MSUS guidelines. A previous study created an atlas of images cataloguing the appearances of healthy children’s joints at different ages. In addition, the Outcome Measures in Rheumatology (OMERACT) task force for pediatric MSUS provides guidelines on vascularity in normal joints and amended grey scale definitions for Doppler images.3


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Even so, the investigators of the viewpoint argued that studies of the efficacy of MSUS in detecting abnormalities in JIA lack adequate evidence and seldom use healthy control participants. Moreover, even randomized controlled trials of MSUS have the same drawback that affect the accuracy of the imaging modality typically exhibiting wide variations because of the importance of operator skill and differences in MSUS equipment.3 Proponents of MSUS in JIA also acknowledge the problems of interoperator reliability and variability across equipment.1

Studies have indicated that MSUS may also be an unreliable diagnostic tool in adult populations. Of note, a study published in 2015 indicated the use of MSUS in a cohort of healthy participants to assess the accuracy of the imaging technique in the evaluation of synovial effusion or synovial hypertrophy. Investigators of this research found that 88% of participants had ≥1 abnormality from MSUS findings, and they noted that the most common finding was synovial effusion, a category omitted from OMERACT group guidelines because of the effusion appearing in the joints of patients without JIA.4 In particular, with MSUS with power Doppler settings, Doppler signals can exist because of healthy children with a growing skeleton having physiologically enhanced blood flow.5 In addition, it was observed that MSUS detects a low level (9%) of abnormalities at the joint vs patient level. Moreover, most patients were seen to have only minor joint pain and MSUS findings consistent with grade 1 in greyscale mode.4 These findings suggest that MSUS may have potential use in diagnosing JIA abnormalities, although conventional radiography, including MRI, may still be the gold standard for the demonstration of structural joint damage in chronic arthritis.5

Researchers across studies broadly agree that improved, earlier diagnosis and treatment of joint abnormalities may prevent chronic deformity and disability in patients with JIA.1,4-6 With MSUS, the greyscale setting provides a 2-dimensional image that increases resolution of scans, while the power Doppler setting more accurately detects effusion.6 In addition, moderate to strong correlations may exist between swelling and abnormalities that are apparent using greyscale and power Doppler settings in MSUS. Furthermore, MSUS shows poor correlations among tenderness, pain on movement, or reduced range of motion, highlighting the limitations of a purely physical examination in establishing joint abnormalities in JIA.

Role of MSUS in Diagnosing Abnormalities in JIA

In some studies, MSUS correctly identified cases of subclinical synovitis, undetected in a physical exam, yet also differentiating between synovitis and tenosynovitis.5,6 The addition of power Doppler settings increases the sensitivity and accuracy of the imaging method by identifying even minimal increases in perfusion present in enthesitis, synovitis, and tenosynovitis.7 Researchers have confirmed the superior accuracy of MSUS to either physical examination or radiography in detecting synovitis, tenosynovitis, and enthesitis, as well as in detecting subclinical synovitis present in patients who show no signs of active disease. Ultimately, MSUS can prove particularly useful in evaluating synovitis at both the anatomic and vascular levels, with the power Doppler setting enabling differentiation between active and inactive joint disease. 5

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Given the scarcity of comparisons with regard to the accuracy of physical examinations, review studies are crucial. Nevertheless, despite the growing use of MSUS, insufficient data exist across studies to evaluate this modality as a validated diagnostic method, even specifically for detecting synovitis. This absence of data does not indicate the drawbacks in the diagnostic use of MSUS, but instead to a lack of consensus on definitions of synovitis in MSUS in patients with JIA, an absence of standardized scanning methods, and a lack of validated scoring systems.8 Significantly, standardized and validated measures, methods, and scores would redress the drawbacks that even the most enthusiastic proponents of MSUS acknowledge – the differences between equipment and reliance on operator experience.1,5

One study specifically focused on intra and interobserver reliability of MSUS in detecting a range of abnormalities in JIA. Contrary to widespread reservations about interoperator concordance, researchers discovered excellent intraobserver concordance for synovitis in all joints in MSUS on greyscale settings. Moreover, for greyscale and power Doppler settings, intraobserver concordance was excellent in detecting tenosynovitis, cartilage damage, and bone erosions. Similarly, intraobserver concordance for synovitis was excellent for all grades, except grade 1, where concordance was still good. More importantly, interobserver concordance was also excellent for diagnosing tenosynovitis and damaged cartilage.9

In comparisons between the accuracy of MSUS and MRI in JIA, MRI confirms the accuracy of MSUS in measuring cartilage thickness in healthy children,10 particularly in the challenging areas of the knee, ankle, and fingers, whereas concordance between physical examination and MSUS has proven to be variable in ≥1 study11; however, MRI is superior to MSUS in detecting bone erosions.12 This outcome is unsurprising, given the overall greater precision of MRI, but also with significant drawbacks, including costs, limitations in the number of joints that can be scanned, and challenges presented by movements that are common during MRI scans in children.1,6

Ultrasonography has other useful applications, including educating young patients by showing them the appearance of both healthy and damaged joints. This exposure, as a pilot study revealed, led to a 25% increase in young patients’ adherence to prescription refills for both disease-modifying antirheumatic drugs and injectable anti-tumor necrosis factor drugs, which have an average adherence of only 56%. Moreover, 50% of the trial patients underwent changes to their therapies, according to a 63% disparity between experienced rheumatologists’ physical examinations and MSUS imaging of joints, with MSUS indicating more joint abnormalities.13

What the Experts Say

“In the hands of an experienced provider, [US’s] positive [effect] on diagnosis and treatment cannot be understated,” noted Emily Brunner, MD, assistant professor of pediatrics and medicine at the University of Pittsburgh. “US cannot replace a physical exam, however, it’s certainly synergistic when combined with [one].”

Lucio Ventura-Rios, MD, medical specialist in internal medicine and rheumatology and expert in musculoskeletal MSUS said, “In favor of the use of ultrasonography in JIA, I can say that: samples from 32 patients in reliability studies are adequate, should not be underestimated, and the superiority of ultrasound over clinic has been demonstrated in all of them. We know the difficulties of using a comparator like MRI in children, but that does not reduce the reliability of the MSUS technique. On the other hand, we know perfectly well that the presence of the Doppler signal must be within the synovitis area to be considered valid, that is why the OMERACT definitions are fundamental to homogenize the evaluations. I consider that Cimaz’s arguments [3] do not have a solid basis to say that ultrasound has limitations in the diagnosis of JIA.”

References

1. Song H. Keeping up with the progress in the diagnosis and management of pediatric rheumatic diseases. World J Pediatr. 2020;16(1):1-4.

2. Caporali R, Smolen JS. Back to the future: Forget ultrasound and focus on clinical assessment in rheumatoid arthritis management. Ann Rheum Dis. 2018;77(1):18.

3. Cimaz R, Giani T, Caporali R. What is the real role of ultrasound in the management of juvenile idiopathic arthritis? Ann Rheum Dis. 2020;79(4):437-439. 

4. Padovano I, Costantino F, Breban M, et al. Prevalence of ultrasound synovial inflammatory findings in healthy subjects. Ann Rheum Dis. 2016;75(10):1819.

5. Magni-Manzoni S, Malattia C, Lanni S, et al. Advances and challenges in imaging in juvenile idiopathic arthritis. Nat Rev Rheumatol. 2012;8(6):329.

6. Brunner E, Ting T, Vega-Fernandez P. Musculoskeletal ultrasound in children: Current state and future directions. Eur J Rheum. 2020;7(1):S28-S37.

7. Cimmino MA, Grassi W. What is new in ultrasound and magnetic resonance imaging for musculoskeletal disorders? Best Pract Res Clin Rheumatol. 2008;22(6):1141.

8. Collado P, Jousse‐Joulin S, Alcalde M, et al. Is ultrasound a validated imaging tool for the diagnosis and management of synovitis in juvenile idiopathic arthritis? A systematic literature review. Arthritis Care Res. 2012;64(7):1011.

9. Ventura-Ríos L, Faugier E, Barzola L, et al. Reliability of ultrasonography to detect inflammatory lesions and structural damage in juvenile idiopathic arthritis. Pediatr Rheum. 2018;16(1):58.

10. Damasio MB, Boavida P, Lambot-Juhan K, et al. Imaging in juvenile idiopathic arthritis (JIA): An update with particular emphasis on MRI. Acta Radiol. 2013;54(9):1015.

11. Bhanu DK, Varghese J. Role of imaging in evaluation and management of juvenile idiopathic arthritis: A prospective cohort study. Int J Res Med Sci. 2018;6(11):3516.

12. Malattia C, Damasio MB, Magnaguagno F, et al. Magnetic resonance imaging, ultrasonography, and conventional radiography in the assessment of bone erosions in juvenile idiopathic arthritis. Arthr Rheum. 2008;59(12):1764.

13. Favier LA, Ting TV, Modi AC. Feasibility of a musculoskeletal ultrasound intervention to improve adherence in juvenile idiopathic arthritis: A proof-of concept trial. Ped Rheum. 2018;16(1):75.