Ultrasound Assessment of Pathologies in Psoriatic Arthritis
Ultrasound Assessment of Pathologies in Psoriatic Arthritis
In the present study, we propose two new ultrasound composite scores for the assessment of PsA specific inflammatory and structural lesions. Both composite scores had adequate convergent construct validity, yielded reliable results and the inflammatory elements revealed sufficient sensitivity to change. We found the bilateral score (PsASon22) more sensitive than the unilateral composite score (PsASon13) to detect PsA-specific pathologies whereas the latter was faster to accomplish.
The major strengths of our composite scores are the inclusion of all currently defined Ps-related ultrasound pathologies into the scores, and the data driven identification of joints, peri-articular structures and entheses, except for a few manual selections aimed at the improvement of the feasibility of the scores. The German U7 and the Italian five-targets scores, the two other ultrasound composite scores previously applied in PsA, were developed on a basis of clinical experience and focus on fewer sites and less PsA-specific pathologies than our instruments.
Our data demonstrate that palmar scans of wrists and plantar scans of feet are dispensable for the ultrasound composite scores, whereas the investigation of palmar and dorsal sites of fingers is required to achieve sufficient sensitivity to identify PsA-specific pathologies. Similar data were reported for the assessment of the rheumatoid hand, whereas a comparison between plantar and dorsal scans of feet has not been performed in other cohorts so far.
We did not include dactylitis into the composite scores, because of the lack of an established ultrasound definition. Earlier studies suggested that the combination of arthritis and tenosynovitis is the underlying pathology of dactylitis, whereas recent ultrasound and magnetic resonance imaging data indicate that isolated tenosynovitis, soft tissue oedema and/or collateral tendon enthesitis are frequently observed in dactylitic fingers and toes. An outcome measures in rheumatology (OMERACT) project aimed at the agreement on a new ultrasound definition of dactylitis is currently underway, and a revision of our composite scores may be considered once such a definition has been validated.
MTP1 was included into the composite scores because we frequently found GSS and PD-j changes at this site. Earlier studies in PsA and RA also reported a high prevalence of inflammatory changes at MTPs; however, we recognize potential overestimation of PsA-related synovitis at that site as MTP1 is also frequently affected by osteoarthritis and because there were some cases of concomitant gout mimicking PsA flares. We did not systematically record ultrasound signs of crystal arthropathies in our patients, but emphasise that such a study should be performed in the future. Similarly, PIP and DIP joints may be inflamed either due to PsA or (secondary or concomitant) symptomatic osteoarthritis, and it is currently impossible to reliably identify the true driver of inflammation by means of imaging methods alone. This uncertainty also relates to RA-specific ultrasound scores, and we do currently not know whether ultrasound-verified synovitis caused by the primary disease or (secondary/concomitant) osteoarthritis has a different impact on clinical and structural outcomes in RA and PsA.
We observed a higher sensitivity of the bilateral versus the unilateral composite score for the detection of inflammatory and structural changes, but at the cost of time. In situations, where a high sensitivity is less relevant (for example, use of sonography to monitor treatment response) the unilateral score may be preferred, whereas for remission assessment the bilateral ultrasound score may produce more valuable results. In RA, subclinical arthritis was of high prognostic value regarding clinical relapses and progression of erosions, and we are currently investigating the relevance of ultrasound-verified inflammation for patients' related outcomes in PsA. A further refinement of the ultrasound scores based on the results of this study (for example, by inclusion of sites with a high significance for the prediction of structural progression) cannot be excluded at this stage.
To test convergent construct validity, we correlated the inflammatory and structural components of the ultrasound scores with clinical measures of disease activity and disability, respectively. We applied the PASDAS, CPDAI and DAPSA as markers of clinical activity recognizing that none of these instruments have yet been established as the gold standard. HAQ better correlated with erosions than with osteophytes, whereas in RA the loss of cartilage was the most important factor contributing to patients' disability.
Among individual components of the GUIS, the GSS/GSE correlated best with clinical activity and revealed the highest sensitivity to change during follow up. This observation may be related to the facts that peripheral arthritis was present in the majority of patients (74.7% had active joint disease according to CPDAI at baseline), that joint disease highly impacts clinical composite scores and global measures of disease activity and that GSS/GEE had the largest variability among the GUIS components. Also, we observed that both ultrasound scores were generally more sensitive to detect GS than PD changes at joints and entheses, possibly explained by a high prevalence of GS-abnormalities even in PsA patients with low or no clinical activity.
The major limitation of our study is the relatively low clinical disease activity of the cohort leading to a possible underestimation of the sensitivity to change of the inflammatory elements. Previously proposed ultrasound scores in PsA and RA were validated in patients with high disease activity at baseline and subsequent treatment with biological agents. Consequently, dramatic changes in disease scores were observed resulting in better sensitivity to change in the ultrasound composite scores by statistical means. The low disease activity in our cohort may also explain the relatively weak association between inflammatory items of the ultrasound composite scores and clinical factors. We previously concluded from an RA study that the strength of association between clinical and ultrasound measures diminishes as patients are in or close to remission. Nevertheless, our ultrasound scores resulted in sufficient sensitivity to change and convergent construct validity, given that the comprehensive assessment of 68-joint/14-entheses did not produce better results than the reduced scores.
Other limitations of this study are the moderate size of the cohort, the relatively long disease duration, the single-centre design and the use of the as yet unvalidated 68-joint/14-entheses score as a reference for the development of the composite scores. Also, we did not test the responsiveness of structural components of the scores because of the short follow-up period and the absence of paired results from other imaging methods. Future studies with a long-term (preferentially multicentre) design, the inclusion of various patients' subgroups (early disease, different clinical manifestations and new treatment with biologics) and the possibility to compare ultrasound data with other imaging methods are needed for external validation of our data.
Another interesting finding of this study is the better reliability of bilateral versus unilateral composite scores. This observation can be explained by the fact that scores with high variability of results (resulting from a larger number of sites included in the bilateral score) yield better statistical associations than scores with a narrow range. The overall reproducibility of our composite scores, however, was comparable to that of previous RA- and PsA-specific scores.
Discussion
In the present study, we propose two new ultrasound composite scores for the assessment of PsA specific inflammatory and structural lesions. Both composite scores had adequate convergent construct validity, yielded reliable results and the inflammatory elements revealed sufficient sensitivity to change. We found the bilateral score (PsASon22) more sensitive than the unilateral composite score (PsASon13) to detect PsA-specific pathologies whereas the latter was faster to accomplish.
The major strengths of our composite scores are the inclusion of all currently defined Ps-related ultrasound pathologies into the scores, and the data driven identification of joints, peri-articular structures and entheses, except for a few manual selections aimed at the improvement of the feasibility of the scores. The German U7 and the Italian five-targets scores, the two other ultrasound composite scores previously applied in PsA, were developed on a basis of clinical experience and focus on fewer sites and less PsA-specific pathologies than our instruments.
Our data demonstrate that palmar scans of wrists and plantar scans of feet are dispensable for the ultrasound composite scores, whereas the investigation of palmar and dorsal sites of fingers is required to achieve sufficient sensitivity to identify PsA-specific pathologies. Similar data were reported for the assessment of the rheumatoid hand, whereas a comparison between plantar and dorsal scans of feet has not been performed in other cohorts so far.
We did not include dactylitis into the composite scores, because of the lack of an established ultrasound definition. Earlier studies suggested that the combination of arthritis and tenosynovitis is the underlying pathology of dactylitis, whereas recent ultrasound and magnetic resonance imaging data indicate that isolated tenosynovitis, soft tissue oedema and/or collateral tendon enthesitis are frequently observed in dactylitic fingers and toes. An outcome measures in rheumatology (OMERACT) project aimed at the agreement on a new ultrasound definition of dactylitis is currently underway, and a revision of our composite scores may be considered once such a definition has been validated.
MTP1 was included into the composite scores because we frequently found GSS and PD-j changes at this site. Earlier studies in PsA and RA also reported a high prevalence of inflammatory changes at MTPs; however, we recognize potential overestimation of PsA-related synovitis at that site as MTP1 is also frequently affected by osteoarthritis and because there were some cases of concomitant gout mimicking PsA flares. We did not systematically record ultrasound signs of crystal arthropathies in our patients, but emphasise that such a study should be performed in the future. Similarly, PIP and DIP joints may be inflamed either due to PsA or (secondary or concomitant) symptomatic osteoarthritis, and it is currently impossible to reliably identify the true driver of inflammation by means of imaging methods alone. This uncertainty also relates to RA-specific ultrasound scores, and we do currently not know whether ultrasound-verified synovitis caused by the primary disease or (secondary/concomitant) osteoarthritis has a different impact on clinical and structural outcomes in RA and PsA.
We observed a higher sensitivity of the bilateral versus the unilateral composite score for the detection of inflammatory and structural changes, but at the cost of time. In situations, where a high sensitivity is less relevant (for example, use of sonography to monitor treatment response) the unilateral score may be preferred, whereas for remission assessment the bilateral ultrasound score may produce more valuable results. In RA, subclinical arthritis was of high prognostic value regarding clinical relapses and progression of erosions, and we are currently investigating the relevance of ultrasound-verified inflammation for patients' related outcomes in PsA. A further refinement of the ultrasound scores based on the results of this study (for example, by inclusion of sites with a high significance for the prediction of structural progression) cannot be excluded at this stage.
To test convergent construct validity, we correlated the inflammatory and structural components of the ultrasound scores with clinical measures of disease activity and disability, respectively. We applied the PASDAS, CPDAI and DAPSA as markers of clinical activity recognizing that none of these instruments have yet been established as the gold standard. HAQ better correlated with erosions than with osteophytes, whereas in RA the loss of cartilage was the most important factor contributing to patients' disability.
Among individual components of the GUIS, the GSS/GSE correlated best with clinical activity and revealed the highest sensitivity to change during follow up. This observation may be related to the facts that peripheral arthritis was present in the majority of patients (74.7% had active joint disease according to CPDAI at baseline), that joint disease highly impacts clinical composite scores and global measures of disease activity and that GSS/GEE had the largest variability among the GUIS components. Also, we observed that both ultrasound scores were generally more sensitive to detect GS than PD changes at joints and entheses, possibly explained by a high prevalence of GS-abnormalities even in PsA patients with low or no clinical activity.
The major limitation of our study is the relatively low clinical disease activity of the cohort leading to a possible underestimation of the sensitivity to change of the inflammatory elements. Previously proposed ultrasound scores in PsA and RA were validated in patients with high disease activity at baseline and subsequent treatment with biological agents. Consequently, dramatic changes in disease scores were observed resulting in better sensitivity to change in the ultrasound composite scores by statistical means. The low disease activity in our cohort may also explain the relatively weak association between inflammatory items of the ultrasound composite scores and clinical factors. We previously concluded from an RA study that the strength of association between clinical and ultrasound measures diminishes as patients are in or close to remission. Nevertheless, our ultrasound scores resulted in sufficient sensitivity to change and convergent construct validity, given that the comprehensive assessment of 68-joint/14-entheses did not produce better results than the reduced scores.
Other limitations of this study are the moderate size of the cohort, the relatively long disease duration, the single-centre design and the use of the as yet unvalidated 68-joint/14-entheses score as a reference for the development of the composite scores. Also, we did not test the responsiveness of structural components of the scores because of the short follow-up period and the absence of paired results from other imaging methods. Future studies with a long-term (preferentially multicentre) design, the inclusion of various patients' subgroups (early disease, different clinical manifestations and new treatment with biologics) and the possibility to compare ultrasound data with other imaging methods are needed for external validation of our data.
Another interesting finding of this study is the better reliability of bilateral versus unilateral composite scores. This observation can be explained by the fact that scores with high variability of results (resulting from a larger number of sites included in the bilateral score) yield better statistical associations than scores with a narrow range. The overall reproducibility of our composite scores, however, was comparable to that of previous RA- and PsA-specific scores.
