Ultrasound Composite Scores for the Assessment of Inflammatory and Structural Pathologies in Psoriatic Arthritis (PsASon-Score)

Anja Ficjan; Rusmir Husic; Judith Gretler; Angelika Lackner; Winfried B Graninger; Marwin Gutierrez; Christina Duftner; Josef Hermann; Christian Dejaco

Disclosures

Arthritis Res Ther. 2014;16(476) 

In This Article

Materials and Methods

Patients

We performed a prospective study on 83 consecutive PsA patients between July 2011 and May 2013. All patients fulfilled the classification for psoriatic arthritis (CASPAR) criteria and had peripheral articular manifestations.[8] The institutional review board of the Medical University Graz approved the study and written informed consent was obtained from each patient.

Two study visits were scheduled 6 months apart. At each visit, complete history and clinical assessments were performed by one of three rheumatologists (AF, JG and JH) unaware of the ultrasound results.[4] The following parameters were recorded: number of tender joints (TJ) and swollen joints (SJ) according to the 66/68 articular index, presence of enthesitis according to the Leeds enthesitis index (LEI) and a clinical counterpart of the Madrid sonographic enthesis index (MASEI) plus lateral epicondyle (cMASEI + E).[9,10] Patients' global assessment of disease activity (PGA), patients' pain assessment (Ptpain) and the evaluator's global assessment of disease activity (EGA) were determined on visual analogue scales (range 0 to 100 mm). We also recorded patients' questionnaires as previously described.[4] Blood samples were routinely tested for erythrocyte sedimentation rate (ESR, range 0 to 10 mm/first hour) and C-reactive protein (CRP) (range 0 to 5 mg/L).

We calculated the following clinical composite scores: the disease activity index for psoriatic arthritis (DAPSA), the composite psoriatic disease activity index (CPDAI) and a modified psoriatic arthritis disease activity score (PASDAS) omitting the short form health survey 36 (SF-36) component, which was not available in our patients.[1–13] In addition, we applied the minimal disease activity (MDA) criteria (5 of the 7 following items: TJ ≤1, SJ ≤1, Psoriasis activity and severity index (PASI) ≤1, Ptpain ≤15 mm, PGA ≤20 mm, health assessment questionnaire (HAQ) ≤0.5, tender enthesal points ≤1])[14] and asked the evaluating rheumatologist for an overall judgment of patients' clinical disease activity without using formal criteria or scores (two possible levels: active disease or remission).

Ultrasound Protocol

Sonographic evaluations were performed by one of two rheumatologists (CDe, RH) at the same day of clinical investigation as previously described in detail.[4] Briefly, grey scale (GS) and power Doppler (PD) sonography were performed at 68 joints and 14 entheses using a MyLab Twice ultrasound device (Esaote, Genova, Italy) with two multifrequence linear transducers (6 to 18 MHz and 4 to 13 MHz). GS synovitis (GSS) and PD-signals at joints (PD-j) were subjectively graded from 0 to 3.[15–17] Perisynovitis was investigated by dorsal scans of metacarpophalangeal joints (MCP) 2 to 5 and was graded in GS (GS-perisyn) and PD (PD-perisyn) with 0 = absent or 1 = present.[18] Tenosynovitis was identified in GS (GS-teno) and graded from 0 to 3 (wrists, ankles) or with 0 = absent or 1 = present at small joints. PD-signals related to tenosynovitis (PD-teno) were graded from 0 to 3. Erosions or osteophytes were also semiquantitatively graded from 0–3.[4]

Enthesitis was assessed according to the MASEI investigating the presence and/or extent of erosions, enthesophytes, PD-signals (PD-e) and GS-changes.[9] We considered GS-changes of enthesitis (GSE) as a combined feature including the loss of fibrillar pattern, hypoechoic aspect, bursitis (infrapatellar and/or retrocalcaneal bursa) and/or enthesal thickening. The following anatomical sites were scanned: the insertion of the common extensor tendon at the lateral epicondyle, the distal insertion of the triceps into the olecranon, the quadriceps insertion into the upper pole of the patella, the patellar tendon insertion into the lower pole of the patella and into the tibial anterior tuberosity, the insertion of the Achilles tendon as well as the insertion of plantar aponeurosis into the calcaneal bone.[4] GSS/GSE refers to GSS and GSE and PD-j/e combines PD-j and PD-e scores.

Construction of the Ultrasound Composite Scores

Our aim was to develop ultrasound composite scores (1) that corroborate all currently defined ultrasound pathologies in PsA including GSS, GSE, PD-j, PD-e, GS-perisyn, PD-perisyn, GS-teno, PD-teno, erosions and ostheophytes/enthesophytes at small, middle/large and DIP joints as well as entheses (as appropriate); (2) that have a high sensitivity to detect these PsA characteristic ultrasound features as compared to the comprehensive assessment of 68 joints and 14 entheses; and (3) whose completion is feasible in clinical practice.

We used the 68-joints/14-entheses ultrasound score as a reference for the development of the new composite scores acknowledging that this instrument has not been validated for monitoring PsA patients yet. We constructed a bilateral and a unilateral composite score (focusing on the dominant site) using the Spanish 12-joint and the German 7-joint scores, respectively, as examples.[6,19] For the inclusion of relevant joints and entheses, we applied a hierarchical approach as exemplarily depicted in Additional file 1 http://arthritis-research.com/content/16/5/476/additional and described in the following paragraph.

We conducted separate cycles of the procedure for each of the following anatomical regions and ultrasound pathologies: (1) small joints (defined as MCPs, metatarsophalangeal joints (MTP) as well as proximal interphalangeal joints (PIP) of hands (H-PIP) and feet (F-PIP)): GSS, PD-j, GS-perisyn (MCPs only), PD-perisyn (MCPs only), GS-teno, PD-teno, erosions and osteophytes; (2) DIP joints of the hand (H-DIP) and feet (F-DIP): GSS, PD-j, GS-teno, PD-teno, erosions and osteophytes; (3) large joints (defined as wrists, elbows, shoulders, hips, knees and ankles): GSS, PD-j, GS-teno (wrists and ankles only) and PD-teno (wrists and ankles only); and (4) entheses: GSE, PD-e, erosions and enthesophytes.

Each cycle started with the identification of the joint/enthesis most commonly revealing the ultrasound lesion of interest (for example, the joint that most frequently showed PD-positivity among small joints - MTP1). For the subsequent procedure, we excluded patients with a positive result at this step (in the example: patients with PD signals at MTP1). Among remaining cases, we identified the most frequently affected joint/enthesis again (in the example: cases with a positive PD result at MCP2). The rationale for excluding patients (and not simply searching for the second most commonly affected site among all cases) was to eliminate strong correlations between joint/enthesis, thus, maximizing the gain of sensitivity by any new site. We repeated this procedure n-times until a combination of sites reached ≥90% sensitivity to detect the corresponding ultrasound abnormality as compared to the 68-joint/14-entheses score. In case the gain of sensitivity by the inclusion of a new item was <20% or <10% for the bilateral or unilateral composite scores, respectively, or the overall prevalence of the finding at a given site was <5%, the selection process was terminated earlier. The rationale for premature termination was the prevention of mechanistic inclusion of sites with a negligible contribution to the overall performance of the composite scores potentially limiting the feasibility of the scores.

Next, we tested whether dorsal or palmar/plantar scans at H-PIPs, H-DIPs, MTPs, F-PIPs, F-DIPs and wrists, as well as medial/lateral or suprapatellar scans at knees, were dispensable for the composite scores. For this purpose, we analysed the proportion of ultrasound abnormalities exclusively detected by dorsal or palmar/plantar scans as well as by medial/lateral or suprapatellar scans of knees. Scans with a yield of <20% were omitted. MCPs were not subject to this analysis, because both palmar and dorsal scans are required to investigate the composite core elements peri- and tenosynovitis, respectively.

Statistical Analysis and validation of the Ultrasound Composite Scores

Statistical analysis was performed using SPSS (version 20.0). Descriptive statistics were used to summarize the data. For continuous non-parametric data, we show the median and range whereas for parametric data, the mean and standard deviation are depicted. Comparisons between independent groups were conducted using the Mann-Whitney U-test and paired data were analysed with the Wilcoxon test (non-parametric data) or Student's t-test (parametric data). Paired categorical data were analysed with the McNemar test.

For validation, we tested inflammatory (that is, GSS/GSE, PD-j/e, GS-Peri, PD-Peri, GS-Teno, PD-Teno) and structural elements (erosions, osteophytes/enthesophytes) of the new ultrasound scores separately. In addition, we constructed a global ultrasound inflammation subscore (GUIS) adding the results of GSS/GSE, PD-j/e, GS-perisyn, PD-perisyn, B-teno and PD-teno.

Convergent construct validity was investigated by the correlation (using Spearman's rank correlation test) of inflammatory items (including GUIS) with clinical parameters of disease activity, and by correlating structural components with the HAQ (analysing the total cohort as well as patients in clinical remission separately in order to adjust for the activity related component of disability[20]).

Sensitivity to change was determined for the inflammatory components (including GUIS) only, as for structural elements the 6-months follow-up period was considered to be too short for the detection of any alterations. We compared the changes of the inflammatory subscore from baseline to the 6-months follow-up visit between patients with stable clinical disease activity (that is, active or inactive disease at both visits) and those being active at baseline and achieving remission (as determined by the evaluating physician) or MDA at follow up. We also calculated Cohen's d effect-size statistic and the standardized response means (SRMs) of the total cohort versus patients in whom clinical disease activity improved.[21] Changes of the inflammatory elements were additionally correlated with alterations of clinical composite scores and its components. Inter-rater reliability of the ultrasound composite scores was determined by serial assessments of 10% of patients by two investigators (CDe, RH) and using the intraclass correlation coefficient (ICC).

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