Ultrasonography, magnetic resonance imaging, radiography, and clinical assessment of inflammatory and destructive changes in fingers and toes of patients with psoriatic arthritis

Arthritis in small joints is common in psoriasis-associated arthritis (PsA), and the clinical distinction from rheumatoid arthritis (RA) can be difficult [1]. Improved therapy options and knowledge of the importance of early initiation of aggressive treatments to optimize long-term outcome in patients [2–5] have led to an increasing focus on developing new sensitive diagnostic and monitoring tools. Imaging modalities such as ultrasonography (US) and magnetic resonance imaging (MRI) appear promising. MRI can detect inflammation and bone destruction in joints earlier than projection radiography (x-ray) in PsA, RA, and spondyloarthritis can [6–8]. US is a tool increasingly used by clinicians, including rheumatologists, but the US data on small joints in PsA are very limited [8, 9]; in particular, the validation of the findings is minimal. The aim of the present study was to assess US for the detection of inflammatory and destructive changes in finger and toe joints, tendons, and entheses in patients with PsA by comparison with MRI, x-ray, and clinical findings.

A total of 845 joints were examined by US, 300 by MRI, and 795 by x-ray.

Ultrasonography observations in PsA and RA patients and CTRLs

The observations by US in PsA and RA patients and CTRLs are listed in Table 1. In particular, it was noted that the DIP joints of patients with PsA had more pathological findings than RA patients; especially, no bone changes (erosions and proliferations) were present in the RA patients. Bone changes found in the MTP joints were primarily at the medial side of the 1st MTP joint. In CTRLs, nine erosion-like changes were seen by US (Figure 3). All were located at the radial and ulnar side of the 2nd and 3rd PIP joints and the 5th MCP joints and at the medial side of 1st MTP joints. In the finger joints, the size of the bone cortex defect was below 12 mm; in the MTP joints, the size was below 20 mm. Bone proliferations were found in two CTRL DIP joints. Synovitis was common in both groups of patients, although we found a tendency toward more synovitis in the MCP and PIP joints in RA patients. A high frequency of synovitis was registered in MTP joints, including in CTRLs. The frequency of tenosynovitis was generally higher in RA than PsA patients, whereas insertional changes and capsular/extracapsular changes were found more frequently, but not exclusively, in PsA.

	All	Psoriasis-associated arthritis	Rheumatoid arthritis	Healthy control persons
Bone erosions
MCP joint	12%	13%	18%	3%
PIP joint	12%	14%	3%	13%
DIP joint	3%	4%	0%	0%
MTP joint	15%	15%	24%	6%
Bone proliferations
MCP joint	4%	6%	0%	0%
PIP joint	8%	12%	3%	0%
DIP joint	9%	13%	0%	5%
MTP joint	5%	5%	4%	6%
Synovitis
MCP joint	22%	19%	50%	3%
PIP joint	13%	13%	23%	3%
DIP joint	18%	22%	23%	3%
MTP joint	44%	43%	56%	34%
Tenosynovitis
MCP joint	7%	4%	23%	0%
PIP joint	18%	16%	40%	0%
DIP joint	6%	2%	20%	3%
Insertional changes
Extensor tendons	8%	12%	3%	3%
Flexor tendons	8%	7%	18%	0%
Capsular/extracapsular changes	9%	7%	25%	0%

Two hundred fingers (196 MCP, 199 PIP, and 200 DIP joints) and 250 MTP joints were examined. The distribution was as follows: psoriasis-associated arthritis = 60 fingers (56 MCP, 59 PIP, and 60 DIP joints) and 150 MTP joints; rheumatoid arthritis = 20 fingers (20 MCP, 20 PIP, and 20 DIP joints) and 50 MTP joints; and healthy control persons = 20 fingers (20 MCP, 20 PIP, and 20 DIP joints) and 50 MTP joints. DIP, distal interphalangeal; MCP, metacarpophalangeal; MTP, metatarsophalangeal; PIP, proximal interphalangeal.

Agreement between ultrasonography, MRI, x-ray, and clinical examination

The agreements between US, MRI, and x-ray for bone changes are listed in Table 3, and the agreements between US, MRI, and clinical examination for inflammatory changes are listed in Table 4. The absolute agreement between the imaging modalities was generally high for bone changes (median 95%; range 78% to 100%) and was lowest for erosions in MTP joints. The absolute agreements between US and MRI for inflammatory changes were slightly lower (median 91%; range 73% to 100%) and were lowest for synovitis and tenosynovitis in the PIP joints. In contrast, the kappa values were higher for inflammatory changes (median 0.51; range 0.04 to 1.00) than for bone changes (median 0.40; range -0.08 to 0.66). X-ray findings that were not revealed by US included erosions in 3 MCP joints (PsA), 13 PIP joints (10 PsA and 3 RA), and 8 DIP joints (PsA) and proliferations in 3 DIP joints (PsA). In the 2nd–4th MTP joints, x-ray detected 6 erosions that were not found by US (4 PsA and 2 RA). Most of the erosions visible by x-ray and not by US were in the non-MRI-examined hand. However, 3 x-ray erosions (all in PsA: 1 MCP and 2 DIP joints) and 2 proliferations (both PsA: 2 DIP joints) were located in the MRI-examined hand and were not registered by MRI (Figure 4). In 2 of the erosions, the anatomy was not fully covered. US versus clinical examination agreements and MRI versus clinical examination agreements were generally low (median 65%; range 38% to 100%) and were lowest for MTP joints. Generally, agreements on the absence of findings were more frequent than agreements on the presence of findings.

To our knowledge, this is the first study to examine small joints in PsA using high-end US and comparing it with contrast-enhanced MRI, x-ray, and clinical examination. A higher frequency of DIP joint changes was found by US in the PsA patients compared with RA patients. In particular, DIP joint bone changes were found exclusively in PsA. Furthermore, bone proliferations were more common and tenosynovitis was less frequent in PsA than RA. For other pathologies, no disease-specific pattern was observed. US and MRI were more sensitive to inflammatory and destructive changes than x-ray and clinical examination, and US showed a high interobserver agreement for bone changes and a lower interobserver agreement for inflammatory changes (Figure 1). A high absolute agreement (85% to 100%) for all destructive changes and a more moderate absolute agreement (73% to 100%) for the inflammatory pathologies were found between US and MRI.

In this study, US revealed synovitis more frequently in MCP and PIP joints and bone erosions less frequently in PIP joints in the RA group than in the PsA group, whereas Fournié and colleagues [13] reported minimal differences in the amount of erosion and synovitis in MCP and PIP joints of PsA and RA patients. Fournié and colleagues [13], as in our study, reported more tenosynovitis and a few osteoarthritic changes (2 of 21 patients) in the RA group and only erosive DIP joint changes in the PsA group. However, they exclusively found extrasynovial changes in PsA patients, which we also detected in 3 of the 5 RA patients (60% confirmed by MRI). Larger studies are required to provide final conclusions. Erosion-like changes were detected by US in 5% of the CTRL joints (6 in fingers and 3 in MTP joints) in our study (Figure 3). Szkudlarek and colleagues found erosion-like changes in 1% of the MTP joints [14] and 0% of the finger joints (MCP and PIP) [15], whereas Døhn and colleagues [7] found erosion-like changes in 38% (6 of 16) and Wakefield and colleagues [16] in 1% (1 of 100) of the examined MCP joints. Five of the 6 erosion-like changes found in our study were located at the radial or ulnar side of the 2nd and 3rd PIP joints and were all very small. Schmidt and colleagues [17] did a circumferential scan of the 2nd PIP joints on 102 CTRLs and reported no erosive changes. Døhn and colleagues [7] suggested that US may be too sensitive, as MRI and computed tomography (CT) could not confirm any of the erosion-like changes found by US. Similarly, none of the US erosion-like changes in our study was confirmed by MRI. The changes may be explained by a high US sensitivity, but some may be physiologic bone notches mistaken for erosions. Future studies with CT as the standard reference method or longitudinal prognostic US studies can provide stronger evidence on bone changes. Both synovitis, especially in MTP joints [14, 15], and tenosynovitis [17, 18] have been reported in CTRLs. Szkudlarek and colleagues [14, 15] reported synovitis in 8% of MTP joints compared with 34% in our study and 2.5% in MCP and PIP joints compared with our 6%. Schmidt and colleagues [17] found signs of tenosynovitis, defined as a hypoechoic rim around 97% of the 2nd flexor tendons, whereas we detected this in only 3%. However, in advance, we excluded minimal changes in our calculations (Materials and methods). The fact that both US1 and US2 found a high frequency of MTP joint synovitis indicates that this observation was truly frequent in our control population. Our high frequency of MTP synovitis in CTRLs may be partly caused by asymptomatic osteoarthritis (OA), as one third are found in the 1st MTP joint, which is often involved in OA. Another contributing cause may be that the applied definitions of synovitis were too sensitive. However, the definitions of MTP synovitis suggested by Koski and colleagues [19] and Schmidt and colleagues [17] also included some of the cases of MTP synovitis in CTRLs, which were found using our definitions. Our results were obtained using US from dorsal, palmar/plantar, and lateral projections. Further studies are needed to determine whether examination from one or more planes can be omitted without marked loss of sensitivity.

In the present study, US and MRI were more sensitive than x-ray and clinical examination in both PsA and RA, which is in agreement with previous findings in RA [7–9, 14–16, 18, 20, 21]. It is of major interest whether bone changes, especially proliferations, found in DIP joints in PsA can be distinguished from bone changes found in OA. This has been addressed by Tan and colleagues [22], who reported that DIP joints on MRI more frequently showed enthesitis enhancement, entheseal erosion, extracapsular changes, and diffuse bone edema in PsA than in OA. We did not examine an OA group, but bone proliferations and insertional changes found in DIP joints of two 63-year-old CTRLs were probably caused by asymptomatic OA. Furthermore, all bone proliferations found in CTRL MTP joints were located on the medial side of the 1st MTP joint, which is a frequent location of OA. The same was the case in the RA group, suggesting concomitant OA as the cause, whereas only three of the seven proliferations found in the PsA group were located there.

US is often criticized for being operator-dependent. Our analysis of interobserver agreement showed a higher agreement for both inflammatory and destructive changes (median 96%) than seen in a European League Against Rheumatism (EULAR) interobserver study [23] in which 14 experienced ultrasonographers examined fingers and wrist (median 73%). The pattern of higher kappa values for bone changes than for inflammatory changes found in our study is concordant with other studies [10, 23].

US and MRI showed high concordance (85% to 100%) for all destructive changes and a more moderate concordance (73% to 100%) for the inflammatory pathologies. This lower agreement for inflammatory changes has also been reported by others [8, 14, 15]. Szkudlarek and colleagues [15] found an overall agreement for synovitis of 76% (versus 82% in our study). In the EULAR study, the overall agreement between US and MRI for fingers and wrist was 73% [23]. The agreement between US and MRI for tenosynovitis was low. Contributing causes may be that US can detect small tendon sheath effusions (especially at the PIP joints) that may not show post-contrast enhancement on MRI [24] and that it can be difficult to distinguish synovitis from tenosynovitis by US. The latter very probably also contributes to the rather low US interobserver reproducibility for synovitis and tenosynovitis.

X-ray is the routine imaging modality for following the destructive changes in clinical practice in patients with arthritis. Many RA studies have shown higher sensitivity of US than x-ray for detecting erosions in RA patients [15, 16, 21, 24], without loss of specificity [15]. Our US sensitivities for erosions, when MRI was considered the standard reference method, showed the same tendency, although not as clearly as in RA [15]. A contributing cause to the lower sensitivity in our study could be that we examined smaller anatomical structures (DIP joints and entheses included). Also, on MRI, detecting such changes may be difficult. This explains why x-ray found some bone changes that were not revealed by US and MRI and why US detected some pathologies (small bone proliferations, DIP synovitis, and insertional changes) more frequently than MRI. In particular, the distinction of capsular enhancement from extracapsular enhancement was difficult by MRI. However, this was met by scoring the two together. The present results were obtained with a 0.6-tesla magnet, and MRI data that are even more detailed may be obtained with higher field strengths (1.5-tesla or 3.0-tesla MRI). As findings by MRI are minimally validated, it can be debated whether MRI is the ideal standard reference. CT, though not better validated than MRI, is a potentially superior option as a reference method for bone changes. Clinical examination showed lower sensitivity (median 0.25) than US (median 0.50) for the detection of inflammatory changes (synovitis). This is in agreement with several previous reports [8, 14, 15, 18].

The present study has demonstrated that both US and MRI are more sensitive for visualization of inflammatory and destructive changes in fingers and toes of patients with PsA. The US interobserver agreement was high for bone changes but was lower for inflammatory changes, whereas the intermodality (US versus MRI) agreement was moderate to high. In comparison with RA patients, PsA patients showed more DIP joint changes. Furthermore, bone proliferations were more common and tenosynovitis was less frequent in PsA than RA. Even though further studies are needed (for example, on definitions of pathologies, standardization of methods, sensitivity to change, and prognostic value), it seems evident that both US and MRI have major potential for improved examination of joints, tendons, and entheses in fingers and toes of patients with PsA.