Perspective Chapter: Musculoskeletal Ultrasound in Inflammatory Joint Diseases

Abstract

Musculoskeletal ultrasound is a very important and useful tool in daily activity as a rheumatologist. It is also called “the stethoscope of rheumatologists.” It enables the clinician to “see” into and around the joint, as ultrasound can penetrate any tissue except for bone. Even though ultrasound cannot penetrate bone, they are completely reflected by bony surfaces, which allows for the appreciation of bone integrity and the visualization of erosions. Another important aspect of using ultrasound for the evaluation of inflammatory joint diseases is the fact that it can depict inflammation within the musculoskeletal system (by depicting new vessel formation, using the Doppler effect), thus being able to contribute to the early and, even, very early diagnosis of inflammatory joint diseases and, conversely, to the early initiation of treatment that enables the prevention of irreversible disability.

1. Introduction

Ultrasonography (US) is a very important tool to be used in medicine. In rheumatology, its use is embedded in routine daily clinical practice and is called “the stethoscope of the rheumatologist.”

There are some situations in which the “standard” approach to joint disease (i.e., anamnesis, clinical examination, lab tests, and radiographic examination) does not allow making the distinction between inflammatory and degenerative joint diseases, let alone the exact diagnosis of the diseases itself [1]. In such instances, there is a need for additional investigations to make the diagnosis. That is when the US was very helpful.

There are many advantages to using the US in rheumatology, especially inflammatory joint diseases. It is easy to use, it may be used on the bedside, it can be repeated, and it is sensitive to change. Musculoskeletal ultrasound (MSK-US) is the only rheumatological imaging modality that offers a dynamic examination while being a real-time examination, acquiring information as it happens. It is safe, fast, and non-invasive, while allowing for diagnostic procedures (e.g., arthrocentesis and biopsy) and treatment procedures (e.g., injection of different substances into the targeted area). But probably the most important advantage of MSK-US over any other imaging modality is its ability to diagnose the presence of inflammation, via using the Doppler module, as soon as the pathogenic process begins. Last, but not least, MSK-US allows simultaneous examination of multiple anatomical structures and increases the sensitivity of the clinical examination (Table 1) [2].

Multiple advantages of using MSK-US
Reproducible	Very good acceptance
Good cost/effectiveness ratio	Easy doable
Improves sensitivity of clinical exam	Early detection of pathology
Real-time images	Very good acceptance
No radiation	Improved effectiveness of interventions

Table 1.

Advantages of MSK-US (modified from [2]).

MSK-US is validated as a diagnostic tool for rheumatoid arthritis, crystal-induced arthritis, and psoriatic arthritis. It has also been validated for use as a follow-up tool in rheumatoid arthritis and psoriatic arthritis. Very important, because of its sensitivity to change, MSK-US is useful in evaluating response to treatment as well, in rheumatoid arthritis [3, 4]. When evaluating the metacarpophalangeal (MCP) joint for erosions, the intraobserver kappa statistic quotient is 0.75, while the interobserver kappa statistic quotient (which interprets agreement among different observers) is 0.76 [5]. Those quotients imply a good reliability of the observations and are comparable to those of radiologists scoring lesions on mammograms [5]. These reliabilities are dependent on multiple factors, one being the joint that is examined. Therefore, the kappa statistical quotient is 0.76 for the shoulder but 0.28 for the ankle/toes [6]. Another factor is the lesion that is evaluated: the overall agreement for tendon lesions and joint effusions is 91%. It is 83.5% for bursitis, 84% for tenosynovitis, and 87% for erosions [7]. In detecting knee synovitis, MSK-US is more sensitive than clinical examination [8].

There are some downsides to the use of MSK-US, too. The most important one is that it is operator-dependent. As shown above, sometimes, the inter-operator reliability is not that good. As such, there is a need for long, thorough, specialized, and continuous, time-consuming training to achieve expert levels, as it is a very dynamic field. Apart from the specialized operator, expert use of MSK-US involves the use of high-end machines, which are still quite expensive in some parts of the world. Due to the physical properties of ultrasound, they cannot penetrate bone. Consequently, MSK-US cannot be used to describe intra-osseous lesions, only cortical ones. Moreover, some anatomical regions are very difficult to explore on ultrasound [2].

The importance of MSK-US use in the context of inflammatory joint diseases is emphasized by its inclusion in EULAR’s (European Alliance of Associations for Rheumatology) recommendations for the use of imaging in some of the inflammatory diseases management [9, 10].

2. Performing ultrasound examination

2.1 General principles

The most important thing about inflammatory joint diseases is to make the correct diagnosis and treatment as early as possible to avoid irreversible structural damage to the joints. US can produce high-resolution images, distinguishing between different tissues and being able to assess bursae, tendons, ligaments, articular capsules, synovial proliferation, cartilage, and bone surface. Additionally, and of paramount importance, is the ability to assess inflammatory angiogenesis that characterizes inflammatory joint diseases.

EULAR’s standardized procedures for ultrasound imaging in rheumatology [11] provide the general frame for a standardized MSK-US examination. Additionally, OMERACT (Outcome Measures in Rheumatology, former Outcome Measures in Rheumatoid Arthritis Clinical Trials) provides definitions for pathologic US findings [12].

When performing MSK-US, it is recommended we use linear transducers with a frequency ranging between 6 and 14 MHz for deep and intermediate structures and above 15 MHz for superficial ones [10]. There are two main modes to be used when performing MSK-US: B-mode, also termed gray scale (GS) mode, can provide anatomical information of the targeted region, and the Doppler mode (color Doppler or power Doppler) that allows for assessment of inflammatory angiogenesis [13]. When using Doppler mode, as little compression as possible is mandatory to avoid compression of very small vessels newly formed. Because blood flow in these vessels is very slow, the pulse repetition frequency should be less than 1 kHz.

Scanning joints should be performed with the probe oriented parallel or perpendicular to the surface of the bone (bony acoustic landmark) so that the cortical bone appears hyperechoic, bright, and sharp [11]. To avoid anisotropy, the probe should be tilted, angulated, and continually adjusted to maintain the ultrasound beam as perpendicular to the structure (usually a tendon) as possible, especially when the structure changes direction (as happens at the insertion site of tendons).

The probe can be used for compressing the region of interest, distinguishing between a liquid (compressible, that is displaceable) and a solid structure (non-compressible, that is non-displaceable) [11].

When performing MSK-US, a fair amount of gel should be used, especially when scanning superficial structures (e.g., extensor tendons of the hand). The orientation of the transducer is of paramount importance. If the structure to examine has a long axis in the craniocaudal orientation, then its most proximal part is placed on the left side of the screen. When in short axis view, the targeted region should be oriented on the screen as if the sonographist is looking at the patient [11].

MSK-US is a dynamic technique in that it can assess the region of interest in movement (passive or active) but also in that the probe should be translated, rotated, angulated, and tilted to allow the best assessment of the targeted region [11].

2.2 Structure examination and normal appearance

2.2.1 Tendons

The US examination of tendons shall be performed using linear probes with a frequency higher than 10 MHz. Because tendons are prone to anisotropy, care should be taken to maintain a perpendicular position of the probe onto the region of interest. This is particularly true for the attachment of the tendon to the bone (enthesis), where some tendons slightly change their orientation and any change of course of the tendon. Like any other structure examined in MSK-US, tendons should be examined in both longitudinal and transverse planes. In the transverse plane, one should be aware of the small transonic image on the sides of the tendon, which is an artifact (tangential shadow) due to the curved shape of tendons in the transverse view. For tendons with synovial sheath, little probe pressure should be applied to avoid displacement (and missing) of small amounts of fluid in the sheath.

The normal appearance of a transverse scan of a tendon is that of a round/oval-shaped structure, resembling “salt and pepper” (hyper and hypoechoic) due to the fibrillar normal structure of a tendon. In longitudinal scans, they appear like fibrillar linear hyperechoic structures with a parallel disposition (Table 2).

Structure	US appearance
Tendon	Hyperechoic (to the subcutaneous surrounding tissue) fibrillar structure; L-parallel hyperechoic lines; T-hyper/hypoechoic dots (“salt and pepper”); No Doppler signal

Table 2.

US appearance of tendons. L, longitudinal view; T, transverse view (modified from [14, 15]).

Tendons must be examined on a gray scale (B-mode) and in Doppler mode to check for abnormal vascularization. Normal tendons do not have visible vessels. The examiner should pay attention to the Doppler settings for superficial or intermediate/profound tendons.

2.2.2 Enthesis

Enthesis is the complex region where a tendon, ligament, joint capsule, fascia, or muscle attaches to the bone [2]. Enthesis of interest in MSK-US are the fibrocartilaginous ones as they represent the target organ in spondylarthritis where the pathogenic process originates. Fibrocartilaginous entheses are a histologically complex structure of attachment to bone, so complex that the term “entheseal body” was coined at the beginning of the century [16, 17]. By the ultrasonographic definition, enthesis is the region where tendon, ligament, and joint capsule insert over the bone with regular edges and the same appearance and width as the rest of the tendon/ligament/capsule, having a fibrillar linear homogenous echogenicity [18]. The probe used for assessing enthesis is one with high frequency (>10 MHz). The normal US aspect of an enthesis in longitudinal view was aforementioned. In the transverse view, it is similar to the tendon/ligament/capsule it inserts. Nevertheless, when assessing an enthesis using US, one must assess all the components of the “entheseal body”: the tendon, the bone underneath, the bursa (that frequently exists to lower friction between the tendon and the bone), and periarticular tissue [19]. For example, in the case of tendons, the US examination of the enthesis must consider the curvature enthesis usually taken when inserted into the bone. This can translate into malalignment of the transducer with the fibers of the enthesis, thus producing anisotropy. Therefore, whenever examining an enthesis, the probe must be slightly and continuously adjusted in its position over the enthesis. Doppler mode is mandatory, especially if spondyloarthritis is suspected (pay attention to the settings of the Doppler mode). Normal enthesis does not have visible vessels. The enthesis of interest in the evaluation of spondyloarthropathies is the insertion of the tricipital tendon on the olecranon, the insertion of the common extensor of the fingers tendon of the lateral humeral epicondyle, the insertion of the quadricipital tendon on the patella, the superior and inferior insertions of the patellar tendon on the patella and the tibial tuberosity, respectively, the insertion of the Achilles tendon on the calcaneus, and the insertion of the plantar fascia on the inferior aspect of the calcaneus.

2.2.3 Cartilage

As normal cartilage is mainly made of water and has no intrinsic vasculature, the US beam will pass through it without almost any reflection; its normal appearance is, consequently, an intense hypoechoic structure. There are two types of cartilage that are of interest in MSK-US: hyaline cartilage and fibrocartilage. As hyaline cartilage lies over bones, which are totally impenetrable to US (thus constituting bony acoustic landmarks), it can be easily recognized because the profound interface between two structures with highly different acoustic impedance (bone and cartilage) produces an intense echo. Because of the very same physical reasons, the superficial border of the cartilage is more difficult to recognize since the difference in acoustic impedance between the cartilage and the surrounding intraarticular space is less [20]. Depicting the fibrocartilage is even more complicated (e.g., triangular fibrocartilage complex (TFFC) of the wrist). When assessing the cartilage, the choice of the probe’s frequency depends on the depth of the region of interest: the deeper the region, the lower the frequency. The most frequently assessed hyaline cartilages in rheumatic inflammatory diseases are the femoral condyles cartilage and the cartilage of the head of the metacarpal bones. For both, the best position to assess them is in maximum flexion of the knee and of the metacarpophalangeal joints, respectively, because in this position they are best exposed from within other bony structures. As usual, they are examined in longitudinal and transverse view. The US examination must describe its transparency, homogeneity, thickness, the continuity of the interfaces (cartilage/adjacent soft tissue and cartilage/bone), and the subjacent bone profile. The most frequently assessed fibrocartilage is the triangular fibrocartilage complex of the wrist and the menisci of the knees. For the TFFC examination, the hand should be pronated and slightly deviated to the radial side, thus exposing the complex. It is examined only in the longitudinal view because the transverse approach does not bring much supplementary information [21]. As the TFFC is deep, the acoustic window is represented by the tendon of the sixth compartment of the extensor tendons of the hand, the extensor carpi ulnaris tendon, viewed in the longitudinal axis as well. The TFFC is viewed as a triangular, homogenous, hypoechoic (compared to the tendon above) structure lying between the distal head of the ulna and the triquetrum. Because the menisci are between the femur and the tibia, they are not completely depictable in any position. To view the external portion, the knee must be in a neutral position (extension) or slightly flexed (around 30 degrees), with the patient lying in dorsal decubitus [20]. They normally appear triangular shaped (basis—superficial, peak—deep), hypoechoic, homogenous structures. Normally, Doppler mode examination reveals no vessels in the cartilage.

2.2.4 Bone

Due to its abundance in calcium, bones cannot be assessed by US. Nevertheless, MSK-US is very accurate in assessing bone surface [22]. The frequency of the probe depends on the depth at which the bone is localized. The normal appearance of the cortical bone is as a hyperechoic continuous line that generates posterior acoustic shadowing and, sometimes, reverberation artifacts. Bones are examined on a gray scale for the continuity and sharpness of their surface. Special attention must be given to the normal irregularities produced by the foramen nutritive, grooves for tendons or nerves, and sesamoid bones. Usually, most of these structures can be easily recognized, and the foramen nutritive is smooth and oblique to the diaphysis. Doppler mode is helpful in differentiating between nutritive vessels and inflammatory neoangiogenic vessels [23].

2.2.5 Joint capsule, synovial membrane, and joints

The joint capsule, which attaches to the bone at the end of the cartilage and is usually strengthened by ligaments, appears on MSK-US examination as a hypo/hyperechoic curved line above the joint visible in longitudinal view in B-mode examination. Its insertions (enthesis) are better seen than the mid portion.

Under normal conditions, the synovial membrane is extremely thin, so it cannot be visualized by US. It is visible only when it becomes thicker, as in chronic inflammatory joint disease. It is then when Doppler mode is most needed.

Examining a joint with US means examining the profile of the two bones that compose the articulation, the cartilage in between, the capsule, and the synovial membrane. In 2017, EULAR standardized procedures for ultrasound imaging [11]. As per these, the best way to perform wrist joint examination, bearing in mind that we are assessing two joints (radio-carpal and inter-carpal), is placing the transducer longitudinally, on the dorsal aspect, at the level of the radio-lunate and luno-capitate joints (corresponding to the third finger). For the metacarpophalangeal joint, the transducer is placed longitudinally over the midline of the joint and for the elbow joint the transducer is placed longitudinally on the anterior aspect over the coronoid fossa. All these techniques will allow for all or most of the above-mentioned structures to be visualized. The capsule of the glenohumeral joint is merely visible over the posterior recess of the joint. At the level of the ankle, the transducer should be placed over the anterior tibiotalar joint recess, while at the knee, the capsule is visible at the lateral and medial aspect of the tibiofemoral joint [11]. For the hip joint, the transducers should have low frequency and should be large enough to visualize the joint as much as possible. One should be aware that low-frequency transducers are not very reliable for Doppler mode use [24].

2.3 Pathological US findings

To understand and practice MSK-US in inflammatory joint diseases, it is mandatory to know the pathological findings that must be searched for.

Since MSK-US is operator-dependent, it should be as standardized as possible. In this respect, OMERACT has developed standardized definitions to be used when assessing and reporting an MSK-US examination to ensure maximum uniformity of reports [11]. Additionally, in 2005, the OMERACT Ultrasound Working Group (WG) initiated research on definitions and scoring of elementary lesions and US-detected pathologies [12] that have been updated along with the combined EULAR-OMERACT scoring system [25]. The result is a series of definitions and scoring systems for some of the inflammatory joint diseases and other rheumatic inflammatory or degenerative diseases that serve as a basis for diagnosing inflammatory joint diseases using MSK-US in clinical daily practice (Tables 3 and 4) [25].

Type of pathology	Description of US findings
Synovitis	Presence of hypoechoic synovial hypertrophy (SH) (regardless of presence of effusion or Doppler signal)
Tenosynovitis	Abnormal anechoic and/or hypoechoic (relative to the tendon) tendon sheath widening, related to tenosynovial abnormal fluid/hypertrophy. Doppler mode should be used only if there is peritendinous synovial sheath widening on B-mode; Doppler signal can be considered if in two perpendicular planes, within the peritendinous synovial sheath, excluding normal feeding vessel
Enthesitis	Hypoechoic and/or thickened insertion of the enthesis close to the bone (<2 mm from bony cortex) with Doppler signal (if active) and possible structural lesions
Erosion	Intra- and/or extra-articular discontinuity of bone cortex visible in two perpendicular planes (step-down discontinuity in [19])

Table 3.

OMERACT definitions for US-detected pathologies (modified after [25]).

US pathology	Elementary lesion
Synovitis	SH is defined as the presence of abnormal hypoechoic synovial tissue within the capsule that is not displaceable and poorly compressible and that may exhibit Doppler signals
Enthesitis	Hypoechoic increased thickness of enthesis (i.e., tendon insertion <2 mm from bony cortex) that exhibits Doppler signal
Tenosynovitis	Tenosynovial hypertrophy is the presence, in two perpendicular planes, within the synovial sheath, of abnormal hypoechoic (relative to tendon) tissue, not displaceable and poorly compressible, that may exhibit Doppler signal

Table 4.

OMERACT definitions of inflammatory elementary lesions composing the inflammatory US pathologies (modified from [25]).

There are inflammatory joint diseases in which some of the elementary US lesions are useful for diagnosis and/or treatment and are not inflammatory in nature but structural. Since they are used in daily clinical practice, their OMERACT definitions follow (Table 5).

Pathology	Structural elementary lesion
Enthesitis	Erosions, calcifications, enthesophytes at the level of the enthesis
Gout double contour	Abnormal hyperechoic band over the superficial margin of the hyaline cartilage, independent of the angle of insonation, regular/irregular, continuous/intermittent, that can be distinguished from the cartilage interface sign
Gout aggregate	Heterogenous hyperechoic foci maintain their high degree of reflectivity when the gain is minimized or the insonation angle is changed, which occasionally can generate posterior acoustic shadow
Gout tophus	Circumscribed, inhomogeneous, hyperechoic and/or hypoechoic aggregation, with/without posterior shadowing, which may be surrounded by a small anechoic rim
CPPD fibrocartilage	Hyperechoic deposits of variable shape, within the cartilage, fixed or moving along with the fibrocartilage during dynamic assessment
CPPD hyaline cartilage	Hyperechoic deposits of variable size and shape, without posterior shadowing, within the cartilage, fixed or moving along with the hyaline cartilage during dynamic assessment
CPPD tendon	Hyperechoic linear structures, generally without posterior shadowing, within the tendon, fixed or moving along with the tendon during dynamic assessment
CPPD synovial fluid	Hyperechoic deposits of variable size, without posterior shadowing, within the synovial fluid, mobile with joint movement and probe compression

Table 5.

Definitions of structural elementary lesions composing the inflammatory US pathologies (modified from [25]).

Based on those definitions, as previously mentioned, there is a EULAR-OMERACT combined scoring system [25], considering together gray scale appearance and Doppler signal, for synovitis (Tables 6 and 7), tenosynovitis (Table 8), and enthesitis (Tables 9 and 10), separately.

Gray scale (SH) appearance	Grade 0 (normal)	No SH (irrespective of effusion)
	Grade 1 (minimal)	Minimal hypoechoic SH, up to the joint line
	Grade 2 (moderate)	Moderate hypoechoic SH protruding beyond the joint line with concave surface
	Grade 3 (severe)	Severe hypoechoic SH protruding beyond the joint line with convex surface
Doppler (PD) appearance	Grade 0 (normal)	No signals
	Grade 1 (minimal)	<3 single signals OR 1 confluent +2 single OR 2 confluent
	Grade 2 (moderate)	>grade1 BUT <50% of SH area covered by signals
	Grade 3 (severe)	>50% of SH area covered by signals

Table 6.

OMERACT scoring system for synovitis. SH, synovial hypertrophy; PD, power Doppler (modified from [25]).

Grade 0: normal	No SH + no PD
Grade 1: minimal synovitis	Grade 1 SH and/or ≤ grade 1PD
Grade 2: moderate synovitis	Grade 2 SH and/or ≤ grade 2 PD or; Grade 1 SH + grade 2 PD
Grade 3: severe synovitis	Grade 3 SH and/or ≤ grade 3 PD or; Grade 1 or 2 SH + grade 3 PD

Table 7.

EULAR-OMERACT combined scoring system for synovitis. EULAR, European Alliance of Associations for Rheumatology; OMERACT, Outcome Measures in Rheumatology; SH, synovial hypertrophy; PD, power Doppler (modified from [25]).

Grade	B-mode (GS)	Doppler mode
Grade 0	No tenosynovial widening	No Doppler signal
Grade 1	Minimal amount of an−/hypoechoic material within the tenosynovial sheath, in two perpendicular planes, localized or displaceable	Signals in one area of the widened sheath, in two perpendicular planes, excluding normal feeding vessel
Grade 2	Moderate amount of an−/hypoechoic material within the tenosynovial sheath	Signals in >1 area of the widened sheath, in two perpendicular planes, excluding normal feeding vessel
Grade 3	Severe amount of an−/hypoechoic material within the tenosynovial sheath	Signals filling most of the widened sheath in two perpendicular planes, excluding normal feeding vessel

Table 8.

OMERACT combined scoring system for tenosynovitis. GS, gray scale (modified from [25]).

Doppler	0–3
Hypoechogenicity	0/1
Thickened enthesis	0/1
Bone erosion	0/1
Enthesophyte or calcification	0/1

Table 9.

OMERACT combined scoring system for enthesitis with semiquantitative Doppler grading—part 1 (modified from [25]).

Grade 0	0 Doppler signal
Grade 1	< 2 punctiform Doppler signals with no confluent Doppler signal
Grade 2	2–4 punctiform Doppler signal OR 1 confluent Doppler signal
Grade 3	>4 punctiform Doppler signal OR > 1 confluent Doppler signal

Table 10.

OMERACT combined scoring system for enthesitis with semiquantitative Doppler grading—part 2 (modified from [25]).

All this data is mandatory for performing high-quality MSK-US. On one hand, they guide on “speaking the same language,” and on the other hand, they allow appreciation of the efficacy of management of the disease, as they allow comparisons in the same patient between different points in time.

3. Ultrasound examination in rheumatic inflammatory joint diseases

3.1 Rheumatoid arthritis (RA)

The use of MSK-US in rheumatoid arthritis is frequent because it can provide valuable information on diagnosis, differential, disease severity, and monitoring disease course on treatment [26].

As a diagnostic tool, MSK-US can be used in undifferentiated arthritis to help a positive or a differential diagnosis [27]. This is especially important in seronegative patients whose disease could thus remain undiagnosed for a long time.

The features that US can depict in RA are synovial hypertrophy, cortical bone erosions, tenosynovitis and effusion. Padovano et al. showed that effusion without synovial hypertrophy should not be considered inflammatory in nature [28]. The presence of a Doppler signal within the thickened synovium is indicative of active inflammatory disease [29]; it, as well as features of tenosynovitis, predicts the risk of imaging progression of RA [30]. MSK-US is a more sensitive imaging modality for detecting erosions than X-ray examination [31]. MSK-US is very useful in depicting erosion on the fifth MTP joint and the second and fifth MCP joints. Even though the clinical relevance of a discovered erosion is variable (depending on its dimension and location), erosion at the fifth MTP increases the probability of RA diagnosis in arthritic patients [26].

MSK-US can also be used to evaluate disease progression in RA. It has been proven that a high baseline power Doppler US signal at the MCP level is predictive of the development of radiographic erosions over the next year [32].

It is well known that some patients, despite being in clinical remission, continue to progress radiologically [26]. Studies have shown that MSK-US is a very good imaging modality in assessing residual activity in RA patients: patients in clinical remission with residual power Doppler active synovitis are at high risk of progressive joint disease [33]. Moreover, these patients are at increased risk of relapse as compared to those power Doppler negative [34].

MSK-US scanning can be quite a time-consuming approach; that is why the number of joints to scan is always a question. This number depends on the clinical presentation, but there are studies pertaining to the choice and number of joints to be scanned in RA. Naredo et al. suggest the assessment of 12 joints (bilateral wrists, metacarpophalangeal, and proximal interphalangeal II and III of hands and knees) using power Doppler US, as it provides an overall assessment of joints’ inflammation [35].

US has been proven to be useful in monitoring disease activity and response to treatment. It correlates strongly with disease activity score 28 joints (DAS28) and inflammatory serum markers (C-reactive protein and erythrocyte sedimentation rate) [36], and it is also sensible to therapy-induced change, thus being able to influence treatment decisions [37].

Combining clinical examination and MSK-US improves the diagnosis of RA patients, especially when radiology assessment is not conclusive. This allows for an early diagnosis, which is the key to avoiding permanent structural joint damage. It is useful in monitoring disease and appreciating the risk of disease flare (in patients in clinical remission) as well as in guiding treatment decisions.

3.2 Spondylarthritis (SpA)

US use in SpA is merely confined to peripheral SpA since in axial SpA, the US examination of the sacroiliac joints is limited to the posterior part of the joints, thus making magnetic resonance imaging the preferred modality to assess these joints [26]. In fact, US imaging has a greater sensitivity than other imaging modalities and clinical examination to detect peripheral involvement in SpA [33].

Using MSK-US in SpA is peripheral SpA is endorsed by EULAR in its recommendations for the use of imaging modalities in the diagnosis and management of SpA [9]. Published in 2015, these recommendations state that, in peripheral SpA, US can and should be used in diagnosing, monitoring disease activity, and evaluating structural damage.

The features associated with peripheral SpA that are assessable using MSK-US are arthritis, enthesitis, tenosynovitis, and dactylitis.

The US appearance of SpA arthritis is no different than RA’s (Table 3). Using Doppler mode can confirm the intense inflammatory vascularization of the hypertrophied synovium, confirming active disease. This is also true for the US aspect of SpA tenosynovitis, with the additional comment that, in SpA, tenosynovitis is more frequent than in RA.

Enthesitis is considered the hallmark of SpA, since the pathogenic process of the disease appears to start at the level of the enthesis [38]. The definition, the US aspect, and the combined scoring system of enthesis have been described previously (see Tables 3, 9, and 10). Assessing entheseal inflammation has been long shown to have a very good diagnostic value in peripheral SpA [39]. It is noteworthy that, to define it as inflammatory, the lesion should be confined to less than 2 mm from the bone cortex [40], and that structural bone lesions (enthesophytes and erosions) are seen in later stages, while the earlier lesions are those related to the tendon [41]. It should be emphasized that some structures are considered as “functional enthesis,” even though they do not respect the “anatomical” definition in that we cannot find a fibrocartilaginous structure (e.g., the tendon areas around the pulleys) [10]. It is also noteworthy that peritendon inflammation of the extensor digitorum tendon (PTI pattern) and central slip tendon enthesitis at the level of the proximal interphalangeal joint are features specific for psoriatic arthritis (as a form of peripheral SpA) [38]. There are multiple US scores that can be used in assessing enthesitis as per the selection of sites to be assessed: MASEI (Madrid Sonography Enthesitis Index) [42], OMERACT US [40], and GUESS (Glasgow Ultrasound Enthesitis Score) [43].

Dactylitis is a very complex US inflammatory lesion, as it involves many structures; it consists of soft tissue edema, enthesitis of the superficial flexor of the finger tendon, peritendinous inflammation (PTI pattern of the extensor tendon), tenosynovitis of the flexor tendon and arthritis, all located in the same finger or toe, making it a pandigital involvement [44]. There is also a scoring system for dactylitis [45].

3.3 Crystal-induced arthritis

The use of MSK-US in crystal-related joint diseases is supported by its high sensitivity and specificity [46]. Both types of crystal deposits generate reflectivity, thus forming the US image.

Monosodium urate crystal deposits on the surface of the articular cartilage [47]. Because of that, they generate a hyperechoic band on that surface parallel to the contour of the head of the bone and move along with the bone, confirming it belongs to the cartilage. This is the “double contour” sign. The band is visible, irrespective of the angle of insonation (see also Table 5). Also, it is visible along the contours of the cartilage. The double contour sign is visible in most long-standing gouty patients; it is also reversible with treatment. Another US appearance of monosodium urate is the so-called “snowstorm appearance,” which is the presence of numerous hyperechoic spots within an area of echogenicity. This is usually depicted when monosodium urate crystals are present within a synovial effusion. Another possible US finding that may be depicted in chronic gout is gout tophus, which appears as a heterogeneous mass containing hyperechoic foci. Sometimes, they must be differentiated from rheumatoid nodules. Tophi may be found inside tendons, joints, and bursae [46, 48].

In diagnosing calcium pyrophosphate deposits, MSK-US is an accurate tool with a high likelihood ratio and better sensitivity than X-rays [49, 50]. Calcium pyrophosphate crystals deposit inside the hyaline cartilage of the joints (intraarticular), in contrast to monosodium urate crystals (which, as previously noted, are located on the surface of the cartilage). Their appearance is classical at the wrist level, where they can be depicted inside the triangular cartilage and at the knee level (inside the cartilage and the menisci). They can also be viewed inside the hip and the acromioclavicular joints [49, 50].

As with all other MSK-US examinations, the evaluation of deposits must be done both in B-mode and in Doppler mode to assess the presence of inflammation associated with the deposit itself. Also, the evaluation must be performed in 2 perpendicular planes, especially when it is referring to the consequences of the presence of crystal deposits, that is, erosion; as well as with other MSK pathologies potentially producing erosions, lesions produce by crystal deposits must be confirmed in both perpendicular planes.

4. Discussion

Having such a versatile imaging tool in rheumatology as MSK-US represents a very good advantage for clinician rheumatologists. Knowing how to use it is mandatory nowadays. As it is validated for diagnosis in its early stages of inflammatory joint diseases, as well as for follow-up and evaluation of treatment efficacy, MSK-US has to be and is incorporated into daily routine practice.

On the other hand, one must not over-emphasize the role of MSK-US in inflammatory joint diseases since there are some downsides to it. Probably the most important problem with this imaging technique is the need for good training, especially long training. Moreover, no matter the quality of the training, any US image is clearly operator-dependent. This is illustrated by the differences in agreement that arise when several experimented experts examine the same joint in the same patient. It is noteworthy, though, that these “disagreements” also depend on other factors, such as the joint examined.

One of the important advantages of MSK-US is the possibility of exploring joints dynamically. The possibility of examining joint movement while it happens allows for viewing details that can provide diagnostic clues. Moreover, MSK-US is the only at-hand imaging method that permits interventional maneuvers, whether diagnostic or therapeutic.

Of course, MSK-US cannot examine every joint in the body, even in the context of inflammatory joint diseases. That is because of the anatomical situation of some joints, as is the case of the sacroiliac joint, whose inflammatory state in the context of spondyloarthritis is US accessible with great difficulty, even though they are superficially located under the skin. This brings us to the fact that MSK-US, like any other investigation, should be carefully chosen, in the appropriate context, of an inflammatory joint disease. The previous example, pertaining to the sacroiliac joints, is conclusive: in case of suspicion of involvement of those joints, as part of a axial spondyloarthritis, one should prefer magnetic resonance imaging over any other imaging technique, including MSK-US, for diagnostic purposes. On the other hand, if there is a suspicion of enthesitis also in the context of spondyloarthritis, one should choose US over any other imaging method for confirming the peripheral involvement.

5. Conclusions

Ultrasound is a very useful tool for the practicing rheumatologist. It is at hand, rapid, non-invasive, cost-effective, repeatable and allows for dynamic evaluation. It can be used for diagnosis, monitoring and treatment decision making. Its use has opened a new window to the diagnosis and also to a more profound understanding of pathogenetic mechanisms of inflammatory joint diseases, thus allowing for an early diagnosis, followed by an early treatment and, hence, avoidance of irreversible joint damage and disability. It has become an extension of the clinical examination (“rheumatologist’s extended finger” [51]) enabling the treating physician with a more profound view of processes to be influenced by the various and effective treatments of inflammatory joint diseases. Thus, performing musculoskeletal ultrasound is mandatory for any clinician working in the field of rheumatology.

Conflict of interest

The authors declare no conflict of interest.