This prospective study included cross-sectional data on consecutively enrolled patients with PsA, PsO with nail involvement and hand OA. Only DIP-joints 2-5 of the dominant hand were assessed. The study followed the STARD-guidelines (25) and a prespecified protocol, see Supplementary Data S1.
Between 1st of December 2017 and 1st of June 2020, patients with PsA according to the CASPAR criteria (8) and a Nail Psoriasis Severity Index (NAPSI) score ≥5 was enrolled from three rheumatology outpatient clinics located in the Capital Region of Denmark and the Zealand Region in Denmark. Patients with OA and PsO were recruited from the Osteoarthritis-, rheumatology- and dermatology outpatient clinics at Bispebjerg and Frederiksberg Hospital. The PsO patients were diagnosed by a dermatologist and the OA patients by a rheumatologist according to the ACR criteria for hand OA (26).
For eligibility criteria, see Supplementary Table S2. Signed informed consent was obtained from all participants, and the study was approved by the local Ethics Committee of the Capital Region in Denmark on 25-05-2018, Journal-no.: H-18006696 and the Danish Data Protection Agency on 04-06-2018 (VD-2018-149, med I-Suite no.: 6392).
Patient-reported outcome measures (PROM)
The physical function was addressed by the Health Assessment Questionnaire disability index (HAQ-DI) (27). The average joint-related pain, general fatigue and global assessment of disease impact within the last week were assessed by Visual Analog Scales 0-100 mm (VAS) with anchors: 0 = no pain/fatigue/impact and 100 = worst imaginable pain/fatigue/impact.
A trained rheumatologist (JG) with nine years of clinical experience conducted: 66/68 swollen/tender joint count, a Psoriatic Area Severity Index (PASI score), a full NAPSI score (score 0-8 on each nail), and Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index (score 0–16, based on 9 bilateral sites; the inferior patella and tibial tuberosity are considered 1 site) (28). The clinician was blinded to other examinations.
US assessment was performed by an experienced (15 years) and certified sonographer (KE) blinded to the clinical results.
US assessments were performed in the longitudinal plane for DIP-joint 2-5 using a General Electric Logiq E9 (Milwaukee, Wisconsin, USA) and a linear array matrix transducer (9-15 MHz frequency). The choice of the probe was based on the consensus of international experts in ultrasonography in an unpublished web-survey (Supplementary Data S3).
The dorsal and volar aspects of 2nd to 5th DIP-joint was semi-quantitatively scored 0-3 for the presence of Grey-scale SH Color Doppler, NBF and erosions according to the OMERACT standards (29). Flexor- and extensor tendon, nail matrix, nail bed and nail thickness were measured in mm. in the longitudinal plane. The ratio of colored/grey pixels in a predefined region of interest (ROI) was calculated (QAnalysis GE software ver. R6 2.0) and reported as Max-ratio and Min-ratio (30). All US images analysis was done blinded to diagnosis by JG. See Supplementary Data S4 for full US protocol.
Magnetic resonance imaging
The distal phalanges and DIP-joint from the 2nd to 5th fingers were examined in a 3T Siemens Verio® MRI scanner using a semi-flex 16 channel body coil. A modified PsAMRIS-score was used in this study encompassing the DIP-joint: D-PsAMRIS range 0-35.
DCE-MRI images were analysed using DYNAMIKA® software (Image analysis group (IAG), London UK). A 3-dimensional ROI was drawn around the distal phalanges and DIP-joint from 2nd to 5th fingers. The computed output data in the various ROIs comprise the mean of the initial rate of enhancement (IRE), maximum enhancement (ME), number of enhancing voxels (NVoxels) and composite scores: IRE*NVoxels and ME*Nvoxels.
The MRI analyses were performed by a radiologist (MB) with 15 years of experience blinded to diagnosis. For complete MRI protocol and DCE-MRI analysis method, see Supplementary Data S5.
Plain posterior-anterior radiographs of the 2nd to 5th DIP-joint was evaluated for entheseal bone-change and erosions and scored 0-3 (0: no changes and 3: large changes). The images were evaluated by a trained radiologist (AZ) with five years of experience blinded to diagnosis. For protocol, see Supplementary Data S6.
The number of PsA patients was predefined and based on power calculations in the protocol (Supplementary Data 1) to 50 participants, and OA and PsO to at least 10 and less than 20 subjects to detect changes that would be detectable but also occur at a meaningful clinical frequency.
The primary analyses focused on assessing differences between diagnoses (the reference standard) in US, MRI and X-ray assessments (index tests) of the SEC. We analysed all data, i.e. four fingers from each participant. The quantitative and semiquantitative US, MRI and X-ray outcomes were analysed using mixed linear models with diagnosis as a fixed factor (3 levels: PsA, PsO and OA) and participant as a random factor. The binominal outcomes were compared using Pearson Chi-square. Odds Ratio and Risk Ratio assessment were calculated using crosstabs, and differences odds ratios between groups were calculated by Mantel-Haenszel Common Odds Ratio Estimate. The diagnostic properties of the index tests: US, MRI and X-ray, was calculated using logistic regression analyses on the three groups pooled with diagnosis (PsA versus PsO and PsA versus OA) as a dependent variable and the quantitative US, MRI and X-ray outcomes as independent variables. The cut-off points to reliably diagnose PsA is determined using a receiver operating characteristic curve analysis estimating the area under the curve (AUC). No, imputation of missing data was performed.
Intra-observer reliability for the US scores was assessed on 100 randomly chosen DIP-joints scored twice by the same rater (JG) separated by 10 days. The intra-rater reliability was quantified using the intraclass correlation coefficient (ICC) (31,32) and weighted Kappa. The intra-rater reliability was good (lowest ICC: 0.64 and lowest Kappa: 0.73; see Supplementary Table S7).
The analyses were conducted using IBM SPSS Statistics ver. 25.