**2. Principles of ultrasound examination in rheumatology**

Ultrasonography enables detailed examination of anatomical structures, periarticular soft tissue and also blood flow using Doppler modalities**.** The 2017 EULAR standardized procedures for US [3] recommend the use of high-resolution linear transducers with a working frequency between 6 and 14 MHz for deeper structures and a frequency of ≥15 MHz for superficial areas. Probe compression can be used to distinguish compressible from non-compressible tissue, but should be avoided when examining blood flow. Images acquired in the long axis should be oriented with the proximal aspect to the left of the screen, while in the short axis, the structures of interest will be aligned just as the examiner is looking at the patient.

US evaluation can assess bone surface, cartilage, tendons, ligaments, synovial proliferation and bursal effusions. Additionally, soft tissue US will include examination of blood vessels, skin, adipose tissue, peripheral nerves for entrapment or tumors (**Figure 1**) and muscles that can be scanned for inflammation, lesions or fluid collections [8].

**Figure 1.**

*Ultrasound GS images of a median nerve neuroma (a – Longitudinal, b - transverse) and a peroneal schwannoma (c - longitudinal). Arrowhead – Median nerve, arrow – Neuroma, asterisk – Peroneal nerve, S – Schwannoma.*

### *Musculoskeletal and Nerve Ultrasonography DOI: http://dx.doi.org/10.5772/intechopen.102640*

The study of blood flow is important in detecting inflammatory activity and this can be performed using color Doppler or power Doppler modalities [9]. Because in the musculoskeletal US, the blood flow is very slow in the small new vessels formed by inflammatory angiogenesis, the pulse repetition frequency used is low, under 1KHz. Nevertheless, some small vessel blood flow is difficult to detect because the signal intensity can be lower than movement artifacts and will be filtered out [10].

Ultrasonography is examiner-dependent, thus a good clinical experience, knowledge of anatomy, good image acquisition and reading of the ultrasound images, together with pitfalls recognition are needed requirements for a quality examination. The OMERACT task-force group has developed standardized definitions to promote uniformity between US examiners' reports (see **Table 1**).

Additional information during US imaging can be obtained through sonoelastography and contrast-enhanced ultrasonography (CEUS) [11–15]. These two US techniques have been studied and proven their usefulness in certain rheumatic diseases, but nevertheless, they are not so widely used as conventional gray scale (GS) and Doppler modalities. Sonoelastography is used for measuring and quantifying tissue stiffness. This can be applied in various situations such as tendon lesions, myositis, and analysis of soft tissue formations such as gout tophi or rheumatoid nodules [16, 17]. Also, promising results are seen in studies of systemic scleroderma, where skin involvement is correlated with loss of dermal elasticity [5]. CEUS can assess joint inflammation and provides a view of the exact vascular patterns, which can also be visible in inflamed sacroiliac joints [10, 18]. Some studies report the superiority of CEUS compared to power Doppler US in detecting synovial hypervascularity [14, 15]. Compared to the known risks of using contrast agents in MRI and CT, contrast agents used in CEUS have no proof of significant side-effects.

Further use of ultrasonography in rheumatology practice resides in the ability to guide local procedures. These include synovial fluid aspiration, therapeutic injection, nerve blocks or soft tissue biopsy [19]. US guided infiltrations have proven to significantly increase the accuracy of medication placement when compared to infiltration guided by anatomical landmarks [20]. This is also the case in aspiration of small fluid effusions or fluid cavities which have multiple septa. Besides the accuracy of therapy injection, US-guided procedures have a reduced risk of damaging nearby nerves, tendons or blood vessels.


### **Table 1.** *OMERACT definitions of ultrasound lesions [4].*

Despite being highly sensitive to inflammatory features, sometimes US cannot discriminate between underlying diseases, especially when suspecting septic arthritis. Here, arthrocentesis can aid the diagnosis through fluid analysis in Gram stain, culture, as well as polarized microscopy.

### **3. Pathology**

### **3.1 Rheumatoid arthritis**

Musculoskeletal ultrasound is frequently used in clinical practice when approaching a patient with joint pain or during the management of a patient with an established diagnosis of RA. US examination can provide valuable information and is often essential for differential diagnosis. Gutierez et al. established in a study on 204 patients with undifferentiated arthritis that US can help fulfill the ACR 2010 criteria and led to a modified diagnosis in 42.1% of cases [21]. This is very insightful because it points out to a significant proportion of patients, mainly seronegative cases with limited joint involvement that could be underdiagnosed within the first months from symptom onset. The 2013 EULAR recommendations for imaging in RA have taken this into account and highlighted the importance of early detection of inflammation and structural damage in patients with arthritis in at least one joint [1]. 9 out of 10 recommendations included the use of ultrasound. This stands for the potential benefit of US in the whole disease spectrum: detection of subclinical inflammation, prediction of progression, differential diagnosis and disease monitoring [22, 23].

The US features seen in RA include: synovial proliferation, joint effusion, cortical bone erosions (**Figure 2c** and **d**) and tenosynovitis. Among these, the presence of erosions and synovial proliferation are considered more specific (**Figure 2**). Moreover, synovial thickening with an increased power Doppler signal can differentiate between active and inactive inflammation [24]. The presence of active inflammation on US and bone marrow edema on MRI can predict risk for radiological progression even in asymptomatic joints. The potential for predicting erosive damage has also been proven for features of tenosynovitis [25].

There is significant evidence related to residual inflammation in clinical remission which in this case could be considered an unstable remission [26]. This can predict a disease flare or structural damage in asymptomatic cases within one year [27].

A more accurate evaluation of inflammatory features detected in RA patients will include a semi-quantified scoring system. This has proven to be correlated with disease activity and can aid the clinician in follow-up visits. The OMERACT study group provided grading systems for synovitis in both gray scale and Doppler mode [4] (see **Table 2**). In 2017, the EULAR-OMERACT study group integrated them into a combined scoring system for synovitis (see **Table 3**) [28].

For practical reasons, a physician should limit the number of joints included in one ultrasound examination. The exact number of joints that should be assessed will certainly depend on clinical presentation, but some studies have provided guidance for a more efficient imaging session. Naredo and colleagues proposed the examination of 12 joints using power Doppler which can provide an overall assessment of joint inflammation. The sites included bilateral wrists, second and third MCPs, and second and third PIPs of hands and knee joints [30]. In 2009, Backhaus and colleagues proposed a more limited number of joints which formed the German US7 score. This score included the wrists, II and III MCPs and PIPs, II and V MTPs joints of the clinically dominant hand and foot [31].

*Musculoskeletal and Nerve Ultrasonography DOI: http://dx.doi.org/10.5772/intechopen.102640*

### **Figure 2.**

*Synovitis in GS (left images) and with power Doppler (right images) at the level of the wrist (a) and metacarpophalangeal joints (c-f). e – Erosions, ext. – Extensor tendons, mcp - metacarpal bone, p – Phalanx, asterisk – Synovitis.*


### **Table 2.**

*OMERACT scoring system for synovitis [4].*

Musculoskeletal ultrasound has proved a strong correlation with other disease activity markers such as the DAS28 score, ESR or CRP levels [32]. Nevertheless, detection of US inflammation is still possible in the context of DAS28 remission and this could influence treatment decisions [12]. US features are sensible to RA-specific


*SH – synovial hypertrophy; PD – power Doppler.*

*In addition, erosive changes have also been integrated into a 0–3 scale for each individual erosion, based on the maximum length. The scoring ultrasound structural erosion (ScUSSe) system is used as follows: 0 = no erosion, 1 = <2 mm, 2 = 2–3 mm, 3 = >3 mm [29].*

### **Table 3.**

*EULAR-OMERACT combined scoring system for synovitis [28].*

therapies and this has also been proven for local intraarticular steroid injections [24]. Thus, ultrasound is a helpful tool for monitoring treatment response.

### **3.2 Spondyloarthritis**

Imaging tests commonly used in patients with axial spondyloarthritis are based mainly on the detection of sacroiliitis through conventional radiology or MRI. The use of ultrasound in SpA patients becomes relevant in peripheral involvement and especially in patients with psoriatic arthritis (PsA). US features seen in SpA patients include: arthritis, tenosynovitis, enthesitis and dactylitis. As in RA, Doppler mode is useful to confirm active inflammation in the articular and periarticular structures. Compared to RA, tenosynovitis (**Figure 3**) is more prevalent, while enthesitis and dactylitis are considered specific features of SpA.

The presence of the lesions on US can help differentiate PsA from early RA. Moreover, psoriatic arthritis patients have proven some other discriminative

### **Figure 3.**

*Ultrasonography of the tibialis posterior (Tp) tenosynovitis (a-c, asterisk) and at the level of extensor carpi radialis brevis (ECRB) and extensor pollicis longus (EPL). mm – Medial malleolus.*

*Musculoskeletal and Nerve Ultrasonography DOI: http://dx.doi.org/10.5772/intechopen.102640*

### **Figure 4.**

*Ultrasonography of the metacarpophalangeal joints in GS mode (left) and power Doppler (right), with periextensor tendon inflammation (PTI pattern - asterisk). mcp – Metacarpal bone, p – Phalanx, ext. – Extensor tendon.*

features such as peritendon extensor digitorum tendon inflammation (**Figure 4**) and central slip enthesitis at the PIP joints [33].

The 2015 EULAR recommendations for the use of imaging in the diagnosis and management of SpA [2] have included ultrasound in three recommendations for peripheral SpA regarding diagnosis, monitoring activity and monitoring structural changes, as follows:

• *Recommendation 2 for peripheral SpA*

Peripheral arthritis, tenosynovitis and bursitis may be **detected** by **US** or MRI. Furthermore, those imaging techniques may be used to detect peripheral enthesitis, which might support the **diagnosis** of SpA.

• *Recommendation 5 for peripheral SpA*

**US** with high-frequency color or power Doppler and MRI may be used to **monitor disease activity** in peripheral SpA, the decision on when to repeat US/MRI depending on the clinical circumstances.

• *Recommendation 6 for peripheral SpA*

When the clinical scenario requires monitoring of structural damage in peripheral SpA, MRI and/or **US might provide additional information**, besides conventional radiography.

The OMERACT Ultrasound Task Force published in 2013 a consensus regarding ultrasound score for tenosynovitis (see **Table 4**). A four grade-semiquantitative scoring system is proposed for both gray-scale (grade 0, normal; grade 1, minimal;


**Table 4.**

*OMERACT ultrasound task force scoring system for tenosynovitis using Doppler mode [30].*

grade 2, moderate; grade 3, severe) and Doppler mode (grade 0, no Doppler signal; grade 1, minimal; grade 2, moderate; grade 3, severe) [30].

Enthesitis is broadly defined as inflammation of the fibrocartilaginous tissue located at the insertion points of tendons (**Figure 5**), ligaments and the joint capsule on bone surface. US features related to enthesitis that have met the 2018 OMERACT consensus [34] include: hypoechogenicity, increased thickness of enthesis, erosions and calcifications/enthesophytes and Doppler signal at insertion. Increased tendon thickness, hypoechogenicity and shadowing of the fibrillar pattern are seen in earlier phases of enthesitis, while cortical bone changes, in the form of erosions and enthesophytes, are related to later stages [35]. Moreover, lesions should be restricted to <2 mm from cortical bone [34]. Nevertheless, distinguishing physiologic entheseal changes in active adults from disease-related lesions may be difficult. Also, lower extremity entheses are prone to mechanical loading, especially in obese patients [36].

When examining enthesis sites for inflammation, a selective approach is required. This will take into account the more accessible areas, present symptoms and potential confounding factors. Various research groups have proposed different sets of enthesis scoring systems. These include the: GUESS - Glasgow Ultrasound Enthesitis Score [37], MASEI - Madrid Sonography Enthesitis Index [38], GRAPPA US - proposed entheseal sites by the GRAPPA Ultrasound Working Group [39] and OMERACT US - proposed entheseal sites by the OMERACT Ultrasound Enthesitis Working Group [34].

New research revealed other areas in which we can find structures that can be assimilated to enthesis. Thus, we can consider as functional enthesis the areas of tendons or ligaments that are wrapped around by pulleys, without being attached to them and as articular fibrocartilaginous entheses, the synovial joints lined with fibrocartilage [40]. Inflammation of those entheses can be identified by US and can explain pain in specific areas.

Dactylitis, one of the more complex inflammatory lesions seen in SpA, is a pandigital disease that involves joint arthritis, tenosynovitis of the flexors, enthesitis of the

### **Figure 5.**

*Ultrasonography of the tibialis posterior (a, b – Longitudinal aspect) (Tp) enthesitis (arrow) at the level of the navicular tuberosity (N) in GS (left) and power Doppler modes (right) and enthesitis of the patellar tendon (c – longitudinal, d – transverse). PT – Patellar tendon, T – tibia.*

### *Musculoskeletal and Nerve Ultrasonography DOI: http://dx.doi.org/10.5772/intechopen.102640*

superficial flexor of the finger, functional enthesitis, proximal to metacarpophalangeal joint (periextensor tendon inflammation) and soft tissue edema (**Figure 6**) [36, 41]. Of this spectrum of lesions, tenosynovitis (**Figure 5**) is considered the primary cause for the characteristic dactylitis or sausage-like appearance of the fingers. Flexor tenosynovitis and joint synovitis are the most frequent features seen in 90% of cases [11]. US lesions related to dactylitis evolve over time. Earlier phases are marked by tenosynovitis and lack of joint inflammation, while in later stages, joint synovitis is more prevalent in comparison to an absent or minimal tenosynovitis [42].

Dactylitis has a relevant role in the early diagnosis of PsA and has also been used as an outcome measure in clinical trials. This has prompted the development of sonographic scores for dactylitis, such as the DACTOS score. It is a composite score which includes the following: peritendinous inflammation of the extensors (PTI), evaluated in GS and PD at the MCP and PIP joints levels (with the maximum score of 4); soft tissue oedema; flexor tenosynovitis evaluated in GS and PD noted in the most severely affected area of the digit (with the maximum score of 6 for each); the combined score for synovitis (evaluated according to EULAR-OMERACT definitions) at the MCP, PIP, and DIP joints (maximum score of 9) [41]. DACTOS score is sensitive to treatment and correlates well with Leeds Dactylitis Index basic, as well as VAS for pain and functional impairment [43].

### **3.3 Crystal deposition disease**

Gout and chondrocalcinosis are the two main forms of crystal deposition disease in which crystals of different compositions accumulate in the intraarticular space and periarticular soft tissue. In gout, raised uric acid levels in the serum to lead to deposition of monosodium urate (MSU) crystals. Chondrocalciosis, also called pseudogout, is characterized by the deposition of calcium pyrophosphate dihydrate (CPPD) crystals. Apart from the different chemical compositions, the both disorders have specific imaging features on ultrasound [17]. MSU crystals in gout generate a characteristic hyperechoic band on the cartilage surface [44], known as the "double contour sign" (**Figure 7**). The dynamic evaluation of the joint reveals the urate hyperechoic band moving together with the bone, thus confirming the belonging to the bone cartilage. This is observed in the majority of gout patients and is reversible with treatment.

MSU deposits can precipitate in the synovial membrane, in the joint cavity within synovial effusion (**Figure 8a**–**c**), in tendons, bursae and soft tissues. Gout tophi appear as a heterogeneous mass with intermittent hyperechoic foci and can

### **Figure 6.**

*Ultrasound image of a volar aspect of the finger, showing changes specific to dactylitis. pp – Proximal phalanx, mp – Medial phalanx, flt – Flexor tendon, asterisk – Synovitis, e - soft tissue oedema, arrow - enthesitis of the superficial flexor tendon, arrowheads – Flexor tenosynovitis.*

### **Figure 7.**

*"Double contour sign" (arrow head) in US of the metacarpophalangeal (a, b) and knee joints (c, d), in longitudinal (a, b, d) and transverse section (c). mcp – metacarpal bone, p – phalanx, f – femur, pat – patella, asterisk – hyalin cartilage.*

### **Figure 8.**

*a–c. Ultrasound images of gouty synovial effusion at the level of the posterior knee – Popliteal cyst (a - transverse, b - longitudinal) and of the olecranon bursa, with the aspect of the "snowstorm" (anechoic area with hyperechoic spots). d. Gouty tophus (arrowhead), with posterior acoustic shadowing (asterisk).*

be distinguished from lipoma or rheumatoid nodules which are more hypoechoic and homogenous. Features of MSU crystal deposition inside tendons and joints and even tophi (**Figure 8d**) can be detected in the setting of asymptomatic

*Musculoskeletal and Nerve Ultrasonography DOI: http://dx.doi.org/10.5772/intechopen.102640*

### **Figure 9.**

*Ultrasound images of calcium pyrophosphate deposits (arrowheads) in CPPD, inside the knee hyaline cartilage (a, c) and in the triangular fibrocartilage complex (b). F – Femur, TFCC - triangular fibrocartilage complex, asterisk – Hyaline cartilage.*

hyperuricemia. EULAR and ACR recommendations support the use of ultrasound in gout and CPPD due to its high sensitivity and specificity [45–47]. The 2015 EULAR/ACR gout classification criteria recognize ultrasound and dual-energy computed tomography as the main imaging modalities used to accurately identify urate deposition [46].

The 2011 EULAR recommendations for calcium pyrophosphate deposition disease (CPPD) highlight the diagnostic potential of ultrasound with a high diagnosis likelihood ratio and possibly even better sensitivity than those of conventional x-rays [47]. The paper of Filippou demonstrated US to be an accurate tool for discriminating CPPD [48]. The OMERACT US group for CPPD has defined in 2017, the ultrasonographic characteristics of CPPD, in both joints and periarticular tissues [49, 50]. In contrast to gouty deposits appearance, at the surface of the cartilage, in CPPD the deposits are present inside the hyaline cartilage. The most important joints in which we can find CPPD deposits are the wrist (at the level of the triangular fibrocartilage), the knee (meniscus and hyaline cartilage) (**Figure 9**), acromioclavicular and hip joint [50].

### **3.4 Osteoarthritis**

Features of degenerative joint disease are easily recognizable by ultrasound examination. Lesions related to osteoarthritis include varying degrees of cartilage damage and osteophyte formation. Although, conventional x-ray is also commonly used in osteoarthritis diagnosis, it can be fairly limited in earlier phases and lacks the capacity to directly visualize the articular hyaline cartilage. One of

**Figure 10.**

*Ultrasound images of step-up bony prominences, at the level of the interphalangeal (a) and femurotibial (b) joints, suggestive for osteophytes. pp – proximal phalanx, dp – distal phalanx, F – femur, T – tibia, m – meniscus, arrow - osteophyte.*

the hallmarks of osteoarthritis US features is the diminished cartilage thickness. Normally, the hyaline cartilage appears as a well-defined anechoic band, due to increased water content, which lacks internal echoes [17]. US has proven to have higher sensitivity compared to conventional x-ray in the assessment of osteophytes and space narrowing. Early features of OA visible through US include: loss of the sharp contour, asymmetric thinning and changes in echogenicity of the cartilage matrix. Additionally, some forms of OA can display erosive and inflammatory changes [51]. Osteophytes are defined as step-up bony prominence seen in two perpendicular planes (**Figure 10**).

The presence of cortical bone irregularities and bony erosions can lead to difficulties in distinguishing osteophyte formations. Upon detection of osteophytes various scoring systems can be applied. This can be a simple semi-quantitative grading scale, as follows: 0 = No osteophyte, 1 = Marginal osteophyte, 2 = Medium osteophyte, 3 = Large osteophyte. Mortada and colleagues proposed a more detailed scoring system for the severity of knee osteoarthritis (see **Table 5**) [52].

The musculoskeletal US can also be applied for therapeutic purposes in degenerative diseases. Patients with OA can benefit from intra-articular infiltration with hyaluronic acid or glucocorticoid and this can be more accurately performed through ultrasound-guided injections. Besides the immediate release of synovial fluid visible during joint aspiration, inflammatory features have also proven to decrease posttreatment. Hence, ultrasound has become a useful tool in both local treatment and monitoring disease activity.


### **Table 5.**

*Ultrasonographic grading scale for severity of primary knee osteoarthritis by Mortada et al. [52].*
