The management of rheumatoid arthritis (RA) has evolved and improved dramatically over recent decades with a new, pronounced emphasis on early detection and intervention (with disease-modifying anti-rheumatic drugs [DMARDs] and biologic agents)¹ to prevent the types of long-term joint deformity previously synonymous with the condition.² It is now widely accepted that, following the onset of RA, there is a time window in which effective institution of appropriate pharmacological treatment can preferentially alter the progression and outcome of the disease.^3,4 However, prompt, accurate recognition and diagnosis of the condition is paramount to achieving this.⁵

A recent collaborative effort from the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) resulted in the publication of new classification criteria for RA.⁶ While plain film x-rays and MRI imaging are widely utilised to aid diagnosis and management of rheumatic disorders, these guidelines have also recognised the added role that ultrasonography (US) can play in the accurate diagnosis of early pathology in joints that are clinically suspicious for signs of inflammation. 

In patients with clinical symptoms of inflammation, but without the classical exam findings of RA, evidence of inflammation on US has been shown to be an accurate predictor of progression to persistent arthritis or RA.⁷ Evaluation of early clinical symptoms of joint inflammation using US has also demonstrated that the initial diagnosis is often revised based on the sonographic joint findings.⁸ This has the potential to better direct the early pharmacological management in patients and avoid the utilisation of DMARDs and biologics in those patients whose disease process would not directly benefit from them. 

ACR/EULAR criteria

ACR/EULAR criteria for defining remission in RA have also been published recently.⁹ Although these criteria do not directly recommend US as part of a standard assessment for remission, several studies have indicated that many patients, despite clinically normal joints, may have residual evidence of inflammation when scanned.^10,11 

A recent systematic review on the topic of remission in RA demonstrated that, despite a clinical diagnosis of remission, most patients (between 73-95%) retained residual evidence of inflammation on US.¹² Whether these patients warrant more aggressive treatment based on this sub-clinical inflammation is a question currently being addressed by a number of different research groups. 

US has, in fact, been proven to be more effective than clinical examination in identifying synovitis in affected or unaffected joints.^13,14

History of ultrasonography in the diagnosis of RA

The idea that US could be used as part of the diagnostic work-up in RA is a relatively new concept with the first reported description of synovitis using this imaging modality documented in 1978.¹⁵ Since then, with advances in US technology, reductions in the cost of scanning machinery and increased availability, the modality has become more acceptable to rheumatologists.¹⁶

The end of the 20th century brought with it increased interest among rheumatologists in relation to their utilisation of US, and the EULAR Working Group for Musculoskeletal Ultrasound was founded.¹⁷ This group published guidelines intended to standardise interpretation of US images in RA.¹⁸ This work prompted an international cohort to establish a further taskforce, Outcome Measures in Rheumatology (OMERACT), which has continued to develop standardised guidelines particularly focusing on developing an US scoring system for assessment of synovitis.^19,20

Synovitis and bone erosion on ultrasonography

Synovitis

The application of US in RA has focused primarily on early detection, grading and treatment of synovitis. The idea that US is more accurate in detecting synovial inflammation over clinical palpation and examination is based on the fact that US can visualise synovium, which is only minimally thickened.^21,22 This type of synovial inflammation can be visualised using simple greyscale US and appears as synovial hypertrophy (hypoechoic or isoechoic) or as a synovial effusion (anechoic).²³

Greyscale US was the first modality used to visualise inflamed joints, however, a shortcoming in its utilisation was that despite accurately visualising features of inflammation it could not differentiate between acute and chronic changes. 

Vascular proliferation

Progression in the development of US technology has resulted in the introduction of both power and colour Doppler which have allowed for assessment of microvascular blood flow in inflamed joints. Power Doppler has been proven to accurately assess joint hypervascularity and shows good correlation with the findings of histological specimens²⁴ as well as MRI synovial enhancement.^25,26 

This specific US modality has allowed for even earlier detection of joint changes²⁷ and the identification of increased power Doppler signal at baseline assessment predicts that a patient is 12 times more likely to go on to develop radiographic change over the preceding year versus an individual without evidence of such hyperaemia.²⁸ In fact, longitudinal use of power Doppler has been shown to demonstrate a stronger correlation with radiographic progression than either clinical or laboratory parameters (rheumatoid factor or anti-citrullinated protein antibody) and has a predictive value for radiographic outcome.^29,30

Contrast-enhanced US has provided an even more intimate picture of the inflamed joint and is exquisitely accurate in differentiating acute synovitis from inactive articular thickening. It is also effective in delineating increased vascular proliferation in the inflamed joint.³¹ Scoring systems have been developed by individual researchers in order to try to quantify greyscale synovial hypertrophy as well as Doppler joint hyperaemia.^32,33 However, the current semiquantitative scoring systems can be quite time-consuming (depending on the number of joints which need to be evaluated) and significant inter- and intra-operator variability can exist in the interpretation of images. An atlas has been published which gives recommendations and examples of scores for a large number of joints³⁴ and OMERACT/EULAR are currently working in tandem to try to develop a common consensus on a practical scoring system for synovitis.

Bone erosion

Bone erosions are one of the key pathological hallmarks of RA and evaluation of their presence and progression is a key component in the management of the disease. While plain radiography has long been considered the gold standard evaluation for erosions, US can also play a role in detection and, in fact, delivers results that are more accurate in early disease. 

In early RA, US has been shown to detect 6.5-fold more erosions than that shown by plain radiography.³⁵ US has the advantage of being able to visualise damage in multiple different planes and shows greater sensitivity for cortical erosions.³⁶ The accuracy of US in predicting these erosions has, again, been shown to have an excellent correlation with the results provided by both MRI and CT.³⁷

OMERACT have developed US definitions of bone erosion, although this definition is weakened by a failure to define a size limit. As technology has advanced the ability to delineate the difference between small bone erosions and physiological joint abnormalities has been possible. However, the utility of US in following these erosions longitudinally has yet to be validated.³⁹

Tenosynovitis

Musculoskeletal US has even been shown to have a utility in the assessment of tenosynovitis which can be visualised as an anechoic signal from within the tendon sheath and surrounding hypoechoic synovial tissue.⁴⁰ It has been suggested that US is the gold standard investigation for inflammation within a tendon,⁴¹ providing comparable accuracy versus MRI in early disease and can be used to assess the response of tenosynovitis to treatment.⁴²

The future for ultrasonography in RA

The role of US in the management of RA has still to achieve definitive consensus among physicians. Current discussions around the area of US in the diagnosis of RA have concentrated on the joints which should be assessed when utilising US. Clinically, the ACR recommend that the 66/68 clinical joint count or the reduced 28-joint count be used for evaluating clinical activity of disease. The value of utilising US to assess different joint combinations in RA has garnered significant research interest. Separate groups have investigated the utility of assessing seven,⁴³ 12,⁴⁴ 38,⁴⁵ 44,⁴⁶ and 78⁴⁷ different joint combinations, respectively. 

Each group differed in terms of the joints, bursae and tendons which they assessed. A systematic review on the topic evaluated the difference between using a low number of joints versus a more extensive, time-consuming screen (of up to 78 joints) and found that “reduced joint combinations were highly associated to the 78-joint score”.⁴⁸

In fact, a study by Ellegard et al found that the examination of only one joint (the most affected wrist) represented a valid measure of disease activity in RA patients.⁴⁹ However, dispute still remains as to the optimal number and location of the joints to include in a global US score for RA and the latest OMERACT guidelines on the topic acknowledge that further validation studies are still required.⁵⁰

The potential introduction of three-dimensional (3D) and four-dimensional (4D) imaging in US has some exciting applications in the field of rheumatology. 3D imaging, in particular, is considered an interesting prospect with regards to improving inter-operator reliability. The modality has already been shown to provide excellent correlation in relation to its two-dimensional (2D) alternative⁵¹ with respect to joint inflammation and bone erosion. Inter-operator reliability when interpreting images is also higher using the 3D modality versus 2D.⁵² Fusion imaging, where US images are overlaid on pre-acquired MRI images (or vice-versa) has been suggested as a means to accurately identify consistent bony landmarks which can then be assessed longitudinally.⁵³

US in RA is a cheaper alternative to CT or MRI and also avoids the ionising radiation associated with the former. It has been demonstrated to add valuable information in detecting early joint inflammation, monitoring of therapeutic response and confirmation of clinical remission. The application of this imaging modality will likely become routine in all rheumatology departments with time. 

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