MUSCULOSKELETAL IMAGING 1339 Differentiating Rheumatoid and Psoriatic Arthritis of the Hand: Mul- timodality Imaging Characteristics Accurate diagnosis and therapeutic intervention at an early stage is paramount for the management of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), which are the two major types of in- flammatory arthritis that involve the hand joints. As more disease- specific medications are developed, medication selection according to the correct diagnosis becomes more important. A delay in di- agnosis and inappropriate medication selection may result in poor functional prognosis. However, clinical differentiation between RA and PsA can be challenging and may become largely dependent on imaging interpretation results. Although there is substantial over- lap in the imaging findings of RA and PsA, there are differences in the affected primary target sites, reflected by the various patterns of joint involvement, and different microanatomic localization of abnormalities within a single joint in each disease. Therefore, ap- propriate use of various imaging modalities and accurate image interpretation add significant value to the diagnosis and treatment process. The synovio-entheseal complex is an important concept for understanding the imaging features of PsA. The authors review the different features of RA and PsA of the hands seen with various im- aging modalities, including radiography, US, MRI, and dual-energy CT, with updates on the contemporary role of imaging in diagnosis and treatment. The radiologist should have sufficient knowledge to interpret imaging findings and understand the strengths and weak- nesses of each modality to recommend the appropriate imaging method and differentiate both diseases accurately. © RSNA, 2020 • radiographics.rsna.org Megumi Shiraishi, MD Takeshi Fukuda, MD Takao Igarashi, MD, PhD Tadashi Tokashiki, MD Reina Kayama, MD Hiroya Ojiri, MD, PhD Abbreviations: DIP = distal interphalangeal, IL = interleukin, MCP = metacarpophalangeal, PA = posteroanterior, PIP = proximal interpha- langeal, PsA = psoriatic arthritis, RA = rheuma- toid arthritis, STIR = short τ inversion recovery, TNF-α = tumor necrosis factor-α, VNCa = vir- tual noncalcium RadioGraphics 2020; 40:1339–1354 https://doi.org/10.1148/rg.2020200029 Content Codes: From the Department of Radiology, The Jikei University School of Medicine, 3-25-8 Nishi- Shimbashi, Minato-ku, Tokyo 105-8461, Japan. Presented as an education exhibit at the 2019 RSNA Annual Meeting. Received March 9, 2020; revision requested April 21 and received May 11; accepted May 13. For this journal- based SA-CME activity, the authors, editor, and reviewers have disclosed no relevant rela- tionships. Address correspondence to T.F. (e-mail: [email protected]). © RSNA, 2020 After completing this journal-based SA-CME activity, participants will be able to: Identify the difference in distribution of lesions in RA and PsA. Describe the typical imaging findings of RA and PsA of the hands. Discuss the strengths and weaknesses of different imaging modalities for evalu- ating inflammatory arthritis. See rsna.org/learning-center-rg. SA-CME LEARNING OBJECTIVES Introduction Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are com- mon causes of chronic inflammatory diseases of the hand joints. It is known that bone erosion can be seen in early RA (1), and recent studies report that even a 6-month delay in treatment initiation af- fects functional prognosis in PsA (2). Therefore, accurate diagnosis at an early stage and early treatment intervention are paramount for both diseases (3). Recently, the development of biologic disease- modifying antirheumatic drugs revolutionized the management of inflammatory arthritis. However, the development of disease-specific drugs signifies the importance of selecting the most suitable medica- tion according to the correct diagnosis. For each disease, there are classification criteria that have been widely used for clinical trials. However, these are not always suit- able to use for clinical diagnosis because these classification criteria sacrifice sensitivity by setting high specificity to prevent patients with a false-positive diagnosis from participating in the study (4). In early stages, both diseases may not present with typical symptoms. Furthermore, up to 30% of patients with RA are reported to have negative test results for rheumatoid factor, and many test results are This copy is for personal use only. To order printed copies, contact [email protected]
Differentiating Rheumatoid and Psoriatic Arthritis of the Hand: Multimodality Imaging Characteristics
Jan 06, 2023
Accurate diagnosis and therapeutic intervention at an early stage
is paramount for the management of rheumatoid arthritis (RA)
and psoriatic arthritis (PsA), which are the two major types of inflammatory arthritis that involve the hand joints. As more diseasespecific medications are developed, medication selection according
to the correct diagnosis becomes more important. A delay in diagnosis and inappropriate medication selection may result in poor
functional prognosis.
Welcome message from author
However, clinical differentiation between RA and PsA can be challenging and may become largely dependent on imaging interpretation results. Although there is substantial overlap in the imaging findings of RA and PsA, there are differences in the affected primary target sites, reflected by the various patterns of joint involvement, and different microanatomic localization of
abnormalities within a single joint in each disease
Transcript
Differentiating Rheumatoid and Psoriatic Arthritis of the Hand: Mul- timodality Imaging Characteristics
Accurate diagnosis and therapeutic intervention at an early stage is paramount for the management of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), which are the two major types of in- flammatory arthritis that involve the hand joints. As more disease- specific medications are developed, medication selection according to the correct diagnosis becomes more important. A delay in di- agnosis and inappropriate medication selection may result in poor functional prognosis. However, clinical differentiation between RA and PsA can be challenging and may become largely dependent on imaging interpretation results. Although there is substantial over- lap in the imaging findings of RA and PsA, there are differences in the affected primary target sites, reflected by the various patterns of joint involvement, and different microanatomic localization of abnormalities within a single joint in each disease. Therefore, ap- propriate use of various imaging modalities and accurate image interpretation add significant value to the diagnosis and treatment process. The synovio-entheseal complex is an important concept for understanding the imaging features of PsA. The authors review the different features of RA and PsA of the hands seen with various im- aging modalities, including radiography, US, MRI, and dual-energy CT, with updates on the contemporary role of imaging in diagnosis and treatment. The radiologist should have sufficient knowledge to interpret imaging findings and understand the strengths and weak- nesses of each modality to recommend the appropriate imaging method and differentiate both diseases accurately.
©RSNA, 2020 • radiographics.rsna.org
Megumi Shiraishi, MD Takeshi Fukuda, MD Takao Igarashi, MD, PhD Tadashi Tokashiki, MD Reina Kayama, MD Hiroya Ojiri, MD, PhD
Abbreviations: DIP = distal interphalangeal, IL = interleukin, MCP = metacarpophalangeal, PA = posteroanterior, PIP = proximal interpha- langeal, PsA = psoriatic arthritis, RA = rheuma- toid arthritis, STIR = short τ inversion recovery, TNF-α = tumor necrosis factor-α, VNCa = vir- tual noncalcium
RadioGraphics 2020; 40:1339–1354
Content Codes:
From the Department of Radiology, The Jikei University School of Medicine, 3-25-8 Nishi- Shimbashi, Minato-ku, Tokyo 105-8461, Japan. Presented as an education exhibit at the 2019 RSNA Annual Meeting. Received March 9, 2020; revision requested April 21 and received May 11; accepted May 13. For this journal- based SA-CME activity, the authors, editor, and reviewers have disclosed no relevant rela- tionships. Address correspondence to T.F. (e-mail: [email protected]).
©RSNA, 2020
After completing this journal-based SA-CME activity, participants will be able to:
Identify the difference in distribution of lesions in RA and PsA.
Describe the typical imaging findings of RA and PsA of the hands.
Discuss the strengths and weaknesses of different imaging modalities for evalu- ating inflammatory arthritis.
See rsna.org/learning-center-rg.
SA-CME LEARNING OBJECTIVES
Introduction Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are com- mon causes of chronic inflammatory diseases of the hand joints. It is known that bone erosion can be seen in early RA (1), and recent studies report that even a 6-month delay in treatment initiation af- fects functional prognosis in PsA (2). Therefore, accurate diagnosis at an early stage and early treatment intervention are paramount for both diseases (3). Recently, the development of biologic disease- modifying antirheumatic drugs revolutionized the management of inflammatory arthritis. However, the development of disease-specific drugs signifies the importance of selecting the most suitable medica- tion according to the correct diagnosis.
For each disease, there are classification criteria that have been widely used for clinical trials. However, these are not always suit- able to use for clinical diagnosis because these classification criteria sacrifice sensitivity by setting high specificity to prevent patients with a false-positive diagnosis from participating in the study (4). In early stages, both diseases may not present with typical symptoms. Furthermore, up to 30% of patients with RA are reported to have negative test results for rheumatoid factor, and many test results are
This copy is for personal use only. To order printed copies, contact [email protected]
1340 September-October 2020 radiographics.rsna.org
spondyloarthropathies, PsA is associated with human leukocyte antigen B27 (HLA-B27) and is also related to development of enthesitis (14). Smoking is a well-known risk factor in sero- positive RA, but other factors such as obesity and low socioeconomic status are also reported as potential risk factors (15,16). On the other hand, mechanical stress is regarded as an impor- tant trigger of enthesitis in PsA (17).
T-cell activation is an important pathway in RA, and production of autoantibodies such as rheumatoid factor and ACPA through B-cell activation can be seen from the preclinical phase of RA (18). Activity of these immune cells is controlled by various cytokines and chemo- kines, of which tumor necrosis factor (TNF)-α and interleukin (IL)-6 are the most investi- gated cytokines in RA (18,19). It is known that they synergistically promote not only synovial inflammation but also bone resorption through osteoclast activity (20).
In PsA, overproduction of IL-23 is thought to occur through variable pathways, including the unfolding protein response induced by HLA- B27 misfolding (21). It activates resident T cells within the enthesis and releases cytokines such as IL-17, TNF-α, IL-6, and IL-22. IL-17 and TNF-α have important roles in inflammation, while IL-22 is associated with new bone for- mation in PsA. PsA is usually seronegative for rheumatoid factor and ACPA (22).
A combination of the previously described pathogenesis drives chronic synovitis in RA and enthesitis in PsA. This is reflected by the difference in primary manifesting lesions, such as patterns of joint involvement in each disease, and also by differences in the microanatomical localization of inflammation within a single joint (23–28).
Pathophysiologic difference needs to be con- sidered for appropriate drug selection in RA and PsA. In RA, both TNF-α inhibitors and IL-6 inhibitors showed successful results in inhibit- ing inflammation and structural damages (29). However, in PsA, although TNF-α inhibitors reduced synovitis and enthesitis, IL-6 inhibitors failed to show any dose response in a phase IIb study (30). In contrast, IL-17A inhibitors were effective in improving signs and symptoms of PsA (31), whereas IL-17A inhibitors and IL- 17A receptor inhibitors showed poor efficacy for RA when used as monotherapy (32). Therefore, although IL-17 is thought to play a role in the pathogenesis of RA, it may not play a substantial role in disease development.
Synovio-Entheseal Complex The synovium is thought to be the primary site of inflammation in RA and enthesis in PsA.
also negative for anticitrullinated protein anti- body (ACPA) (5). Other pathognomonic features such as rheumatoid nodules usually appear late in the disease course (5–8). In addition, 10%–15% of patients with PsA develop joint symptoms before psoriasis (9). Therefore, differentiating these pathologic conditions at early stages can be challenging. Imaging modalities such as US and MRI are valuable tools in these situations be- cause they have a higher sensitivity than clinical assessment for detecting inflammatory changes (10,11). The primary target of the initial inflam- mation is thought to be different in each type of arthritis. This difference may be reflected on images. Hence, using various imaging modalities and interpreting images accurately add a signifi- cant value to the diagnosis and treatment process.
With increasing recognition of the impor- tance of imaging in the evaluation of inflamma- tory arthritis, radiologists need to be more aware of the imaging characteristics and strengths of each modality. We review the different imaging features of PsA and RA of the hands seen with various imaging modalities, including radiogra- phy, US, MRI, and dual-energy CT, and provide updates on the contemporary role of imaging in diagnosis and treatment.
Pathophysiology The pathophysiology of RA and PsA is not completely understood, but genetic factors and environmental triggers are thought to have a critical role in the development of these diseases (12). As a genetic factor, HLA-DRB1 alleles are related to disease susceptibility and severity in seropositive RA (13). As with other forms of
TEACHING POINTS The concept of the synovio-entheseal complex helps explain why enthesitis can subsequently lead to adjacent joint capsule synovitis, tenosynovitis, and periarticular inflammation in PsA.
Iodine mapping and VNCa technique at dual-energy CT are the available image processing techniques used to depict in- flammatory lesions in inflammatory arthritis.
Erosion is one of the most important imaging findings in early RA. Erosions in RA typically occur in the bare areas of the joint. This is frequently seen in the MCP joints, where there is an increased likelihood of both synovitis and bone erosion forma- tion on the radial side in early RA.
New bone formation is a key bone change that can be seen in PsA but not in RA. In the joints, it occurs at the periarticular area owing to enthesitis. The surface of the bone erosion and bone proliferation in PsA may have a fluffy appearance.
The extensor tendon, which attaches to the dorsal base of the terminal phalanx after running over the DIP joint, has a small extension referred to as the superficial lamina that covers the nail root. This anatomic link is considered to be associated with inflammation of the nail and DIP joints in PsA.
RG • Volume 40 Number 5 Shiraishi et al 1341
Figure 2. Illustrations demonstrate the anatomic difference in the inflammation sites between RA (a) and PsA (b) at the interpha- langeal joint. In RA, inflammation is localized in the synovium (arrows in a). In PsA, inflammation begins at the enthesis (arrows in b) and may spread to the adjacent synovium (arrowhead in b). Inflammation also spreads outside of the joint more readily in PsA than in RA and causes periarticular inflammation, whereas inflammation in RA is usually localized in the synovium.
gan with the adjacent synovium, such as a joint capsule or bursa. This enthesis organ is called the synovio-entheseal complex (Fig 1). The concept of the synovio-entheseal complex helps explain why enthesitis can subsequently lead to adjacent joint capsule synovitis, tenosynovitis, and periarticular inflammation in PsA (Fig 2).
Imaging Modalities The characteristics of various imaging modali- ties used for the evaluation of inflammatory arthritis, including radiography, US, MRI, and dual-energy CT, are discussed in this section.
Radiography Radiography is a well-established examination for the evaluation of inflammatory arthritis and should be used as the primary tool owing to its accessibility and cost effectiveness. It has many advantages compared with other imaging modalities, such as the ability to image multiple joints simultaneously with minimum radiation exposure. Although detection and assessment of bone changes are the most important reasons for obtaining radiographs, bone changes only become apparent at a later stage in the disease
Enthesis is the attachment site of the ligament, tendon, or joint capsule to the bone. Fibrocar- tilaginous enthesis, which is an interface with a transitional zone of fibrocartilage, is known to be vulnerable in PsA.
The functional role of fibrocartilage is to endure load and sheering force at the enthesis (33). This protective tissue can be found at fric- tion sites where the tendon runs over the bone or at pulleys where the tendons are held in place as they thread through the fibrous tunnel on the volar surface of each finger. The peroneus lon- gus under the lateral malleolus and the extensor tendons of fingers over the phalanx are examples of tendons with fibrocartilage that form func- tional enthesis (34). Although tendons do not attach to the bone at these sites, the term func- tional enthesis was used because of the presence of fibrocartilage, which acts as a stress-absorbing material.
Previously, it had not been clearly addressed why synovitis is frequently found in PsA, when enthesis is supposed to be the primary inflam- matory site. However, McGonagle et al (35) reported that fibrocartilaginous enthesis is not a mere focal insertion but forms a functional or-
Figure 1. Synovio-entheseal complex. The interphalangeal joint has fibrocartilage (red areas) that can be found in the extensor ten- don not only at the tendon attachment site (arrow) but also at the friction site against the bone, which is known as functional enthesis (arrowhead). There is a close relationship between the fibrocarti- lage and the joint capsular synovium (green lines).
1342 September-October 2020 radiographics.rsna.org
course (Fig 3). However, owing to the delay in the patient’s first visit to the rheumatologist from the time of symptom onset, which could range from several months to more than a year (9,10), there is a possibility that minor bone changes on the radiograph can be detected. Radiography can also be used for evaluation of soft-tissue changes such as swelling and calcifi- cation. Furthermore, radiography, which is the easiest imaging modality to perform, should
be considered for joint assessment at regular follow-up for arthritis (36).
Ultrasonography US is the imaging modality of choice for evalu- ating arthritis, even if findings at radiography are unremarkable. For the detection of inflam- matory lesions, US has a higher sensitivity than clinical assessment (37). Doppler US can depict increased blood flow in the joints and can help
Figure 3. Typical imaging findings of RA (a, b) and PsA (c, d). (a) Posteroanterior (PA) radio- graph shows hitchhiker thumb (arrowhead) and subluxation of the second and third metacar- pophalangeal (MCP) joints. Severe joint space narrowing is depicted in the carpal bones. Bone erosion (arrow) is depicted in the bare area (where synovium is in direct contact with bone) of the third MCP joint. (b) Coronal CT image shows bone deformity and ankylosis of carpal bones more clearly than does the radiograph. (c) PA radiograph shows erosion and bone proliferation in multiple joints, with involvement of the distal interphalangeal (DIP) joints. Ray pattern distribu- tion involving whole joints is also depicted in the third finger. (d) Coronal CT image of the third DIP joints shows bone erosion and periarticular bone proliferation more precisely than does the radiograph.
RG • Volume 40 Number 5 Shiraishi et al 1343
grade disease activity (Fig 4) (38). As for bone erosion, several studies suggest that US could depict more erosions in RA when compared with radiography (36,39,40). However, previous stud- ies failed to confirm the increase in sensitivity of US in the detection of bone erosions compared with that of radiography (41,42). Because US is a noninvasive method of investigation and some imaging devices are portable, it can be performed in the outpatient clinic. US also has limitations, such as operator dependence and limited ac- cess to certain joints owing to acoustic shadows, as well as being a time-consuming method for evaluating multiple joints. Moreover, US cannot be used to depict bone marrow edema.
Magnetic Resonance Imaging MRI is also superior to clinical examination in the detection of inflammatory lesions (43) and has a higher sensitivity than radiography and US for detecting bone erosion (36). Coronal and axial T1-weighted images are preferred during the assessment of structural changes in peripheral joints. Water-sensitive sequences such as fat-sat- uration T2-weighted imaging or short τ inversion recovery (STIR) should be included in a stan- dard protocol for inflammatory arthritis, as these sequences are sensitive in detecting inflammatory lesions, including bone marrow edema. Use of contrast material is recommended in the assess- ment of inflammatory lesions such as synovitis and tenosynovitis (Fig 5) (25).
The ability to obtain standardized images and aid in objective assessments are the advantages of MRI compared with those of US. MRI could provide reliable results in clinical trials owing to these features. However, peripheral joints have complex structures that cause magnetic field inhomogeneity that may reduce image quality, such as insufficient fat suppression and image distortion (44).
CT and Dual-Energy CT CT is an effective tool to assess calcification, scle- rosis, and structural changes such as erosion and bone proliferation. CT has been regarded as the standard examination when evaluating structural changes. However, the utility of conventional CT in inflammatory arthritis is limited owing to the inability to delineate inflammatory lesions.
Recently, dual-energy CT has become available in clinical settings and has been applied to various clinical entities. By measuring the attenuation at different x-ray energy levels, dual-energy CT enables the identification of material composi- tion (45). Iodine mapping and virtual noncal- cium (VNCa) technique at dual-energy CT are the available image processing techniques used to depict inflammatory lesions in inflammatory arthritis. On an iodine map, the density of the iodine contrast material that accumulates at the inflammatory site can be emphasized (Fig 6c, 6d).
It has recently been reported that dual-energy CT with iodine mapping is a valid tool for quan- titative assessment of the therapeutic responses of PsA (46). Also, VNCa images can delineate bone marrow edema by subtracting trabecular bone (Fig 6). However, only relatively large bones have been used to investigate its utility, and technical difficulties remain when examining bone marrow edema in small bones, such as the distal phalan- ges. However, the ability to detect inflammatory lesions in addition to the original advantages of CT in assessing structural changes is beneficial.
Figure 4. Longitudinal Doppler US image of the wrist joint in a 63-year-old man with RA shows bone erosion (arrow) and synovial proliferation with Doppler signals. Note the joint effu- sion (arrowhead).
Figure 5. Axial contrast material–enhanced fat-suppressed T1-weighted MR images in a 73-year-old man with RA show synovitis around the carpal bones as an enhancing lesion (ar- rows in a) and flexor tenosynovitis at the carpal tunnel as an enhancing lesion (arrows in b).
1344 September-October 2020 radiographics.rsna.org
Figure 6. MR (a, b) and dual-energy CT (c, d) images of the thumb in a 46-year-old woman with PsA. (a) Coronal STIR MR im- age shows bone marrow edema (arrow) at the metacarpal head of the thumb. Joint effusion, which is suggestive of synovitis, is also depicted in the MCP joint. (b) Coronal contrast-enhanced fat-suppressed T1-weighted MR image shows synovitis (arrow) as an en- hancing lesion. Note that bone marrow edema is also enhancing. (c) Coronal VNCa CT image shows bone marrow edema (arrow) in the corresponding area of the metacarpal head of the thumb. With reference to the MR images, the small bones adjacent to the interphalangeal joint are colored incorrectly on the VNCa CT image owing to technical limitations. (d) Sagittal CT iodine map shows synovitis (arrow) as an enhancing area in the MCP joint.
Major disadvantages of dual-energy CT are ra- diation exposure and limited available facilities.
Systematic Approach to Differentiate RA and PsA of the Hand: Multimodality
Imaging Characteristics The various multimodality imaging character- istics of RA and PsA are discussed in this sec- tion. An “ABCDE” mnemonic (alignment, bone change and bone marrow edema, cartilage dam- age, distribution, and effusion with synovitis or enthesitis) is used to aid in the structural inter- pretation of images.
Alignment Ulnar deviation of the second to fifth MCP joints, including boutonnière deformity (button- hole deformity) and swan neck deformity, is the most frequent type of deformity in RA and may manifest at early stages. A boutonnière defor- mity is characterized by flexion of the proximal interphalangeal (PIP) joint and hyperextension of the DIP joint (47). A boutonnière deformity involves disruption of the central band of the extensor tendon, which normally inserts to the dorsal base of the middle phalanx. The disrup- tion of the central band causes the lateral bands to slide volar to the PIP joint, causing flexion of the PIP joint. The imbalance of force results in hyperextension of the DIP joint. A swan neck deformity is characterized by flexion of the DIP joint and hyperextension of the PIP joint owing to the imbalance of muscle forces. Other defor- mities such as mallet finger and hitchhiker de- formity are more likely to be found in advanced stages of RA (24,48) (Fig 7).
On the other hand, ulnar deviation is rarely seen in PsA. However, severe deformity of the hand such as arthritis mutilans can be seen at the end stage of PsA, as well as in RA (Fig 8). Arthritis…
Accurate diagnosis and therapeutic intervention at an early stage is paramount for the management of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), which are the two major types of in- flammatory arthritis that involve the hand joints. As more disease- specific medications are developed, medication selection according to the correct diagnosis becomes more important. A delay in di- agnosis and inappropriate medication selection may result in poor functional prognosis. However, clinical differentiation between RA and PsA can be challenging and may become largely dependent on imaging interpretation results. Although there is substantial over- lap in the imaging findings of RA and PsA, there are differences in the affected primary target sites, reflected by the various patterns of joint involvement, and different microanatomic localization of abnormalities within a single joint in each disease. Therefore, ap- propriate use of various imaging modalities and accurate image interpretation add significant value to the diagnosis and treatment process. The synovio-entheseal complex is an important concept for understanding the imaging features of PsA. The authors review the different features of RA and PsA of the hands seen with various im- aging modalities, including radiography, US, MRI, and dual-energy CT, with updates on the contemporary role of imaging in diagnosis and treatment. The radiologist should have sufficient knowledge to interpret imaging findings and understand the strengths and weak- nesses of each modality to recommend the appropriate imaging method and differentiate both diseases accurately.
©RSNA, 2020 • radiographics.rsna.org
Megumi Shiraishi, MD Takeshi Fukuda, MD Takao Igarashi, MD, PhD Tadashi Tokashiki, MD Reina Kayama, MD Hiroya Ojiri, MD, PhD
Abbreviations: DIP = distal interphalangeal, IL = interleukin, MCP = metacarpophalangeal, PA = posteroanterior, PIP = proximal interpha- langeal, PsA = psoriatic arthritis, RA = rheuma- toid arthritis, STIR = short τ inversion recovery, TNF-α = tumor necrosis factor-α, VNCa = vir- tual noncalcium
RadioGraphics 2020; 40:1339–1354
Content Codes:
From the Department of Radiology, The Jikei University School of Medicine, 3-25-8 Nishi- Shimbashi, Minato-ku, Tokyo 105-8461, Japan. Presented as an education exhibit at the 2019 RSNA Annual Meeting. Received March 9, 2020; revision requested April 21 and received May 11; accepted May 13. For this journal- based SA-CME activity, the authors, editor, and reviewers have disclosed no relevant rela- tionships. Address correspondence to T.F. (e-mail: [email protected]).
©RSNA, 2020
After completing this journal-based SA-CME activity, participants will be able to:
Identify the difference in distribution of lesions in RA and PsA.
Describe the typical imaging findings of RA and PsA of the hands.
Discuss the strengths and weaknesses of different imaging modalities for evalu- ating inflammatory arthritis.
See rsna.org/learning-center-rg.
SA-CME LEARNING OBJECTIVES
Introduction Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are com- mon causes of chronic inflammatory diseases of the hand joints. It is known that bone erosion can be seen in early RA (1), and recent studies report that even a 6-month delay in treatment initiation af- fects functional prognosis in PsA (2). Therefore, accurate diagnosis at an early stage and early treatment intervention are paramount for both diseases (3). Recently, the development of biologic disease- modifying antirheumatic drugs revolutionized the management of inflammatory arthritis. However, the development of disease-specific drugs signifies the importance of selecting the most suitable medica- tion according to the correct diagnosis.
For each disease, there are classification criteria that have been widely used for clinical trials. However, these are not always suit- able to use for clinical diagnosis because these classification criteria sacrifice sensitivity by setting high specificity to prevent patients with a false-positive diagnosis from participating in the study (4). In early stages, both diseases may not present with typical symptoms. Furthermore, up to 30% of patients with RA are reported to have negative test results for rheumatoid factor, and many test results are
This copy is for personal use only. To order printed copies, contact [email protected]
1340 September-October 2020 radiographics.rsna.org
spondyloarthropathies, PsA is associated with human leukocyte antigen B27 (HLA-B27) and is also related to development of enthesitis (14). Smoking is a well-known risk factor in sero- positive RA, but other factors such as obesity and low socioeconomic status are also reported as potential risk factors (15,16). On the other hand, mechanical stress is regarded as an impor- tant trigger of enthesitis in PsA (17).
T-cell activation is an important pathway in RA, and production of autoantibodies such as rheumatoid factor and ACPA through B-cell activation can be seen from the preclinical phase of RA (18). Activity of these immune cells is controlled by various cytokines and chemo- kines, of which tumor necrosis factor (TNF)-α and interleukin (IL)-6 are the most investi- gated cytokines in RA (18,19). It is known that they synergistically promote not only synovial inflammation but also bone resorption through osteoclast activity (20).
In PsA, overproduction of IL-23 is thought to occur through variable pathways, including the unfolding protein response induced by HLA- B27 misfolding (21). It activates resident T cells within the enthesis and releases cytokines such as IL-17, TNF-α, IL-6, and IL-22. IL-17 and TNF-α have important roles in inflammation, while IL-22 is associated with new bone for- mation in PsA. PsA is usually seronegative for rheumatoid factor and ACPA (22).
A combination of the previously described pathogenesis drives chronic synovitis in RA and enthesitis in PsA. This is reflected by the difference in primary manifesting lesions, such as patterns of joint involvement in each disease, and also by differences in the microanatomical localization of inflammation within a single joint (23–28).
Pathophysiologic difference needs to be con- sidered for appropriate drug selection in RA and PsA. In RA, both TNF-α inhibitors and IL-6 inhibitors showed successful results in inhibit- ing inflammation and structural damages (29). However, in PsA, although TNF-α inhibitors reduced synovitis and enthesitis, IL-6 inhibitors failed to show any dose response in a phase IIb study (30). In contrast, IL-17A inhibitors were effective in improving signs and symptoms of PsA (31), whereas IL-17A inhibitors and IL- 17A receptor inhibitors showed poor efficacy for RA when used as monotherapy (32). Therefore, although IL-17 is thought to play a role in the pathogenesis of RA, it may not play a substantial role in disease development.
Synovio-Entheseal Complex The synovium is thought to be the primary site of inflammation in RA and enthesis in PsA.
also negative for anticitrullinated protein anti- body (ACPA) (5). Other pathognomonic features such as rheumatoid nodules usually appear late in the disease course (5–8). In addition, 10%–15% of patients with PsA develop joint symptoms before psoriasis (9). Therefore, differentiating these pathologic conditions at early stages can be challenging. Imaging modalities such as US and MRI are valuable tools in these situations be- cause they have a higher sensitivity than clinical assessment for detecting inflammatory changes (10,11). The primary target of the initial inflam- mation is thought to be different in each type of arthritis. This difference may be reflected on images. Hence, using various imaging modalities and interpreting images accurately add a signifi- cant value to the diagnosis and treatment process.
With increasing recognition of the impor- tance of imaging in the evaluation of inflamma- tory arthritis, radiologists need to be more aware of the imaging characteristics and strengths of each modality. We review the different imaging features of PsA and RA of the hands seen with various imaging modalities, including radiogra- phy, US, MRI, and dual-energy CT, and provide updates on the contemporary role of imaging in diagnosis and treatment.
Pathophysiology The pathophysiology of RA and PsA is not completely understood, but genetic factors and environmental triggers are thought to have a critical role in the development of these diseases (12). As a genetic factor, HLA-DRB1 alleles are related to disease susceptibility and severity in seropositive RA (13). As with other forms of
TEACHING POINTS The concept of the synovio-entheseal complex helps explain why enthesitis can subsequently lead to adjacent joint capsule synovitis, tenosynovitis, and periarticular inflammation in PsA.
Iodine mapping and VNCa technique at dual-energy CT are the available image processing techniques used to depict in- flammatory lesions in inflammatory arthritis.
Erosion is one of the most important imaging findings in early RA. Erosions in RA typically occur in the bare areas of the joint. This is frequently seen in the MCP joints, where there is an increased likelihood of both synovitis and bone erosion forma- tion on the radial side in early RA.
New bone formation is a key bone change that can be seen in PsA but not in RA. In the joints, it occurs at the periarticular area owing to enthesitis. The surface of the bone erosion and bone proliferation in PsA may have a fluffy appearance.
The extensor tendon, which attaches to the dorsal base of the terminal phalanx after running over the DIP joint, has a small extension referred to as the superficial lamina that covers the nail root. This anatomic link is considered to be associated with inflammation of the nail and DIP joints in PsA.
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Figure 2. Illustrations demonstrate the anatomic difference in the inflammation sites between RA (a) and PsA (b) at the interpha- langeal joint. In RA, inflammation is localized in the synovium (arrows in a). In PsA, inflammation begins at the enthesis (arrows in b) and may spread to the adjacent synovium (arrowhead in b). Inflammation also spreads outside of the joint more readily in PsA than in RA and causes periarticular inflammation, whereas inflammation in RA is usually localized in the synovium.
gan with the adjacent synovium, such as a joint capsule or bursa. This enthesis organ is called the synovio-entheseal complex (Fig 1). The concept of the synovio-entheseal complex helps explain why enthesitis can subsequently lead to adjacent joint capsule synovitis, tenosynovitis, and periarticular inflammation in PsA (Fig 2).
Imaging Modalities The characteristics of various imaging modali- ties used for the evaluation of inflammatory arthritis, including radiography, US, MRI, and dual-energy CT, are discussed in this section.
Radiography Radiography is a well-established examination for the evaluation of inflammatory arthritis and should be used as the primary tool owing to its accessibility and cost effectiveness. It has many advantages compared with other imaging modalities, such as the ability to image multiple joints simultaneously with minimum radiation exposure. Although detection and assessment of bone changes are the most important reasons for obtaining radiographs, bone changes only become apparent at a later stage in the disease
Enthesis is the attachment site of the ligament, tendon, or joint capsule to the bone. Fibrocar- tilaginous enthesis, which is an interface with a transitional zone of fibrocartilage, is known to be vulnerable in PsA.
The functional role of fibrocartilage is to endure load and sheering force at the enthesis (33). This protective tissue can be found at fric- tion sites where the tendon runs over the bone or at pulleys where the tendons are held in place as they thread through the fibrous tunnel on the volar surface of each finger. The peroneus lon- gus under the lateral malleolus and the extensor tendons of fingers over the phalanx are examples of tendons with fibrocartilage that form func- tional enthesis (34). Although tendons do not attach to the bone at these sites, the term func- tional enthesis was used because of the presence of fibrocartilage, which acts as a stress-absorbing material.
Previously, it had not been clearly addressed why synovitis is frequently found in PsA, when enthesis is supposed to be the primary inflam- matory site. However, McGonagle et al (35) reported that fibrocartilaginous enthesis is not a mere focal insertion but forms a functional or-
Figure 1. Synovio-entheseal complex. The interphalangeal joint has fibrocartilage (red areas) that can be found in the extensor ten- don not only at the tendon attachment site (arrow) but also at the friction site against the bone, which is known as functional enthesis (arrowhead). There is a close relationship between the fibrocarti- lage and the joint capsular synovium (green lines).
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course (Fig 3). However, owing to the delay in the patient’s first visit to the rheumatologist from the time of symptom onset, which could range from several months to more than a year (9,10), there is a possibility that minor bone changes on the radiograph can be detected. Radiography can also be used for evaluation of soft-tissue changes such as swelling and calcifi- cation. Furthermore, radiography, which is the easiest imaging modality to perform, should
be considered for joint assessment at regular follow-up for arthritis (36).
Ultrasonography US is the imaging modality of choice for evalu- ating arthritis, even if findings at radiography are unremarkable. For the detection of inflam- matory lesions, US has a higher sensitivity than clinical assessment (37). Doppler US can depict increased blood flow in the joints and can help
Figure 3. Typical imaging findings of RA (a, b) and PsA (c, d). (a) Posteroanterior (PA) radio- graph shows hitchhiker thumb (arrowhead) and subluxation of the second and third metacar- pophalangeal (MCP) joints. Severe joint space narrowing is depicted in the carpal bones. Bone erosion (arrow) is depicted in the bare area (where synovium is in direct contact with bone) of the third MCP joint. (b) Coronal CT image shows bone deformity and ankylosis of carpal bones more clearly than does the radiograph. (c) PA radiograph shows erosion and bone proliferation in multiple joints, with involvement of the distal interphalangeal (DIP) joints. Ray pattern distribu- tion involving whole joints is also depicted in the third finger. (d) Coronal CT image of the third DIP joints shows bone erosion and periarticular bone proliferation more precisely than does the radiograph.
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grade disease activity (Fig 4) (38). As for bone erosion, several studies suggest that US could depict more erosions in RA when compared with radiography (36,39,40). However, previous stud- ies failed to confirm the increase in sensitivity of US in the detection of bone erosions compared with that of radiography (41,42). Because US is a noninvasive method of investigation and some imaging devices are portable, it can be performed in the outpatient clinic. US also has limitations, such as operator dependence and limited ac- cess to certain joints owing to acoustic shadows, as well as being a time-consuming method for evaluating multiple joints. Moreover, US cannot be used to depict bone marrow edema.
Magnetic Resonance Imaging MRI is also superior to clinical examination in the detection of inflammatory lesions (43) and has a higher sensitivity than radiography and US for detecting bone erosion (36). Coronal and axial T1-weighted images are preferred during the assessment of structural changes in peripheral joints. Water-sensitive sequences such as fat-sat- uration T2-weighted imaging or short τ inversion recovery (STIR) should be included in a stan- dard protocol for inflammatory arthritis, as these sequences are sensitive in detecting inflammatory lesions, including bone marrow edema. Use of contrast material is recommended in the assess- ment of inflammatory lesions such as synovitis and tenosynovitis (Fig 5) (25).
The ability to obtain standardized images and aid in objective assessments are the advantages of MRI compared with those of US. MRI could provide reliable results in clinical trials owing to these features. However, peripheral joints have complex structures that cause magnetic field inhomogeneity that may reduce image quality, such as insufficient fat suppression and image distortion (44).
CT and Dual-Energy CT CT is an effective tool to assess calcification, scle- rosis, and structural changes such as erosion and bone proliferation. CT has been regarded as the standard examination when evaluating structural changes. However, the utility of conventional CT in inflammatory arthritis is limited owing to the inability to delineate inflammatory lesions.
Recently, dual-energy CT has become available in clinical settings and has been applied to various clinical entities. By measuring the attenuation at different x-ray energy levels, dual-energy CT enables the identification of material composi- tion (45). Iodine mapping and virtual noncal- cium (VNCa) technique at dual-energy CT are the available image processing techniques used to depict inflammatory lesions in inflammatory arthritis. On an iodine map, the density of the iodine contrast material that accumulates at the inflammatory site can be emphasized (Fig 6c, 6d).
It has recently been reported that dual-energy CT with iodine mapping is a valid tool for quan- titative assessment of the therapeutic responses of PsA (46). Also, VNCa images can delineate bone marrow edema by subtracting trabecular bone (Fig 6). However, only relatively large bones have been used to investigate its utility, and technical difficulties remain when examining bone marrow edema in small bones, such as the distal phalan- ges. However, the ability to detect inflammatory lesions in addition to the original advantages of CT in assessing structural changes is beneficial.
Figure 4. Longitudinal Doppler US image of the wrist joint in a 63-year-old man with RA shows bone erosion (arrow) and synovial proliferation with Doppler signals. Note the joint effu- sion (arrowhead).
Figure 5. Axial contrast material–enhanced fat-suppressed T1-weighted MR images in a 73-year-old man with RA show synovitis around the carpal bones as an enhancing lesion (ar- rows in a) and flexor tenosynovitis at the carpal tunnel as an enhancing lesion (arrows in b).
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Figure 6. MR (a, b) and dual-energy CT (c, d) images of the thumb in a 46-year-old woman with PsA. (a) Coronal STIR MR im- age shows bone marrow edema (arrow) at the metacarpal head of the thumb. Joint effusion, which is suggestive of synovitis, is also depicted in the MCP joint. (b) Coronal contrast-enhanced fat-suppressed T1-weighted MR image shows synovitis (arrow) as an en- hancing lesion. Note that bone marrow edema is also enhancing. (c) Coronal VNCa CT image shows bone marrow edema (arrow) in the corresponding area of the metacarpal head of the thumb. With reference to the MR images, the small bones adjacent to the interphalangeal joint are colored incorrectly on the VNCa CT image owing to technical limitations. (d) Sagittal CT iodine map shows synovitis (arrow) as an enhancing area in the MCP joint.
Major disadvantages of dual-energy CT are ra- diation exposure and limited available facilities.
Systematic Approach to Differentiate RA and PsA of the Hand: Multimodality
Imaging Characteristics The various multimodality imaging character- istics of RA and PsA are discussed in this sec- tion. An “ABCDE” mnemonic (alignment, bone change and bone marrow edema, cartilage dam- age, distribution, and effusion with synovitis or enthesitis) is used to aid in the structural inter- pretation of images.
Alignment Ulnar deviation of the second to fifth MCP joints, including boutonnière deformity (button- hole deformity) and swan neck deformity, is the most frequent type of deformity in RA and may manifest at early stages. A boutonnière defor- mity is characterized by flexion of the proximal interphalangeal (PIP) joint and hyperextension of the DIP joint (47). A boutonnière deformity involves disruption of the central band of the extensor tendon, which normally inserts to the dorsal base of the middle phalanx. The disrup- tion of the central band causes the lateral bands to slide volar to the PIP joint, causing flexion of the PIP joint. The imbalance of force results in hyperextension of the DIP joint. A swan neck deformity is characterized by flexion of the DIP joint and hyperextension of the PIP joint owing to the imbalance of muscle forces. Other defor- mities such as mallet finger and hitchhiker de- formity are more likely to be found in advanced stages of RA (24,48) (Fig 7).
On the other hand, ulnar deviation is rarely seen in PsA. However, severe deformity of the hand such as arthritis mutilans can be seen at the end stage of PsA, as well as in RA (Fig 8). Arthritis…
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