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Purpose: The primary objective of this prospective, longitudinal, observational, single-centre study was to evaluate the association between ultrasound-assessed lesions of dactylitis and the diagnosis of psoriatic arthritis (PsA) in patients with psoriasis (PsO) and hand arthralgia., Methods: We included adult patients diagnosed with PsO with hand arthralgia, with or without other musculoskeletal complaints. They were clinically assessed at baseline, 6 and 12 months by a rheumatologist blinded to the ultrasound findings. At baseline, patients underwent a B-mode (BM) and power Doppler (PD) ultrasound assessment by other rheumatologist blinded to clinical data. The ultrasound evaluation included bilateral detection and scoring of synovitis (3 joints, 0-3), tenosynovitis (flexor tendons, 0-3), enthesitis (9 sites, 0-1), peri‑extensor tendon inflammation (PETI) (0-3), and subcutaneous tissue inflammation (SCTI) (0-3) in the 2nd-5th fingers., Results: Seventy patients [44 women; mean (SD) age 51 (12.4) years] were included, of whom 64 completed the study. Of these, 15 (23.4 %) were diagnosed with PsA during the 12-month follow-up period. At finger level, the presence and amount of baseline BM and PD synovitis, BM tenosynovitis, BM and PD enthesitis, and BM and PD PETI were associated with PsA diagnosis (p < .05). A predictive model including two variables, presence of PD synovitis and BM enthesitis, was found to predict PsA diagnosis (χ2 = 35.38; p < .001) with an accuracy of 89.1 %, a sensitivity of 86.7 % and a specificity of 89.8 %., Conclusions: Ultrasound-assessed lesions of dactylitis were associated with a diagnosis of PsA and the short-term development of PsA in patients with PsO and hand arthralgia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Otto Olivas-Vergara: Speaker fees from UCB Pharma. Lina Martínez-Estupiñán: Currently is employee of Abbvie. Fredeswinda Romero-Bueno: None. Olga Sanchez-Pernaute: None. Javier R. Godo: None. Maria del Carmen Fariña Sabaris: Speaker fees from Almirall, Abbvie, Novartis, Janssen, UCB Pharma, Amgen, Lilly. Belen Ruffin Vicente: None. Agustina Criado Alcazar: None. Pablo E. Borges: None. Sheila Recuero-Díaz: None. Andrea Alvear-Torres: None. Amalia Gil: None. Antía García-Fernández: None. Ana Elena Hoyo Fernández: None. M. Belen Ortega Trompeta: None. M. Isabel Sanchez-Barba Izquierdo: None. Gabriel Herrero-Beaumont: None. Raquel Largo: None. Esperanza Naredo: Speaker fees from Novartis; Research grant from Lilly and Abbvie., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To compare synovial blood flow scoring between different technologies and ultrasound (US) systems in active and inactive rheumatoid arthritis (RA)., Material and Methods: Fifty-nine RA patients underwent B-mode, power Doppler (PD), colour Doppler (CD), B-Flow and High-Resolution (High-Res) PDI assessments of 6 joints with two US systems at two European centres. Each joint was semi-quantitatively scored for all ultrasound parameters. PD, CD and High-Res PDI synovial signal was also quantitatively scored., Results: Correlations between the total score of SH with system 1 and 2 were very high (≥ 0.90, p<0.0001). Baseline correlations between systems for PD and CD total scores were moderate to very high (0.44-0.96, p<0.05). At baseline, there were no significant differences between ultrasound systems for PD or CD semiquantitative-based total scores in active or inactive patients (p>0,05). B-Flow and High-Res total scores were significantly lower than PD or CD total scores (p<0.05)., Conclusion: A high-end and an entry-level US system were interchangeable for scoring SH and showed similar sensitivity and responsiveness in scoring synovial blood flow by PD and CD but not interchangeability. B-Flow and High-Res PDI were responsive, but they showed different sensitivity to detect synovial blood flow compared to conventional Doppler.

Objectives: To assess performance of interstitial pneumonia (IP) with autoimmune features (IPAF) criteria in clinical practice and describe the utility of additional workup in identifying patients with underlying connective tissue diseases (CTD)., Methods: We set a retrospective study of our patients with autoimmune IP, who were allocated to CTD-IP, IPAF or undifferentiated autoimmune IP (uAIP) subgroups according to the updated classification criteria. Presence of the process-related variables comprising IPAF defining domains was scrutinized in all patients, and, when available, the results of nailfold videocapillaroscopy (NVC) were recorded., Results: Thirty nine out of 118 patients, accounting for 71% of former undifferentiated cases, fulfilled IPAF criteria. Arthritis and Raynaud's phenomenon were prevalent in this subgroup. While systemic sclerosis-specific autoantibodies were restricted to CTD-IP patients, anti-tRNA synthetase antibodies were also present in IPAF. In contrast, rheumatoid factor, anti-Ro antibodies and ANA nucleolar patterns could be found in all subgroups. Usual interstitial pneumonia (UIP) / possible UIP were the most frequently observed radiographic patterns Therefore, the presence of thoracic multicompartimental findings as also performance of open lung biopsies were useful in characterizing as IPAF those UIP cases lacking a clinical domain. Interestingly, we could observe NVC abnormalities in 54% of IPAF and 36% of uAIP tested patients, even though many of them did not report Raynaud's phenomenon., Conclusion: Besides application of IPAF criteria, distribution of IPAF defining variables along with NVC exams help identify more homogeneous phenotypic subgroups of autoimmune IP of potential relevance beyond clinical diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Romero-Bueno, Rodríguez-Nieto, Palacios Miras, Martínez Estupiñán, Martínez-Becerra, Vegas Sánchez, Cedeño Díaz, Sánchez-Pernaute and The NEREA Autoimmune ILD Study Group.)

Background:  Digital subcutaneous tissue (SCT) changes are involved in dactylitis, a hallmark feature of psoriatic arthritis (PsA). There are no studies on the ultrasound (US) characteristics of the digital SCT in the general population., Objectives:  To investigate the variability in US-measured thickness (TH) and color Doppler (CD)-detected blood flow of the SCT of the volar aspects of the fingers in a non-psoriatic population and to investigate the impact of the scanning method and demographics and clinical features on these measurements., Methods:  SCT TH and semiquantitative (SQD) and quantitative (QD) Doppler signals were measured in the bilateral second finger at the proximal and middle phalanges in 81 non-psoriatic volunteers [49 female, 32 men; 18-78 years]. Two scanning methods with and without (thick gel layer interposition) probe-skin contact were used. Demographics and clinical features were collected., Results:  There was high variability of SCT TH and Doppler measurements between individuals. All US measurements obtained without probe-skin contact were significantly greater than their corresponding measurements obtained with the probe contacting the skin (p < 0.001). SCT TH was positively related to dominant hand, age, masculine gender, weight, height, body mass index, and alcohol consumption while Doppler measurements were positively related to age and non-dominant hand., Conclusions:  US-measured SCT thickness and Doppler-detected SCT blood flow of the volar aspect of the fingers seem to be highly variable in the non-psoriatic population as well as highly dependent on the US scanning method. This variability is of utmost importance for assessing dactylitis in PsA., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This study aimed to determine by ultrasonography, and cadaveric dissection, whether the firm cords felt by palpation at the sides of the proximal phalanx (PP), actively flexing, and extending the proximal interphalangeal (PIP) joint while keeping the metacarpophalangeal (MCP) joint extended are the lateral bands (LBs) of the extensor apparatus. If so, palpation of the LBs could help evaluate hand conditions that impact the digits' intrinsic muscles. To this end, the PP of the middle and ring fingers of the dominant hand of seven subjects were studied by palpation on both sides. Ultrasonography (US) was performed with a hockey-stick transducer placed on the ulnar side. Five cadaveric hands were dissected, exposing the dorsal extensor apparatus. On palpation, a firm cord was consistently felt at the PP's sides in all subjects. These cords moved widely forward on PIP flexion and backward with PIP extension. By US scanning, the cords corresponded to the LBs. However, the forward movement had only a median of 1.8 mm (range 0.7-3 mm) in the middle finger and a median of 1.1 mm (range 0.3-2.7 mm) in the ring finger compared with an estimated 5-10 mm upon palpation. Cadaveric dissection confirmed the forward movement of the LBs in PIP flexion. We concluded that the firm cords felt at the PP sides are the LBs of the extensor apparatus. We confirmed their movement with the active flexion/extension of the PIP joint. Comparing the wide palpatory and the meager US motion, a haptic illusion of motion may be present., (© 2021 Anatomical Society.)

Objective: To determine the effect of knee flexion and submaximal isometric quadriceps muscle (Q) contraction on the patellar tendon (PT), the infrapatellar fat pad (IPFP), and the deep infrapatellar bursa (IPB) from extension to full flexion., Methods: In Study 1, the dominant knee of seven healthy subjects was studied in full extension and at 60° flexion during relaxation and Q contraction. Each knee was inspected and palpated, the transverse infrapatellar diameter was measured by plicometry, and measurements of the anteroposterior (AP) thickness of the IPFP were made by ultrasound (US). In Study 2, the dominant knee of seven healthy subjects was studied by US in full flexion, and then, at 15° decrements, down to 60° flexion during relaxation and Q contraction. Both studies had IRB approval. Results were analyzed with the Wilcoxon test and descriptive statistics., Results: In Study 1, Q contraction caused straightening of the patellar tendon (PT), a statistically significant widening of the IPFP by plicometry, and an increased AP thickness of the IPFP by US, in both knee positions. In Study 2, in full knee flexion, the PT contacted the tibial cortex in all seven subjects. Upon increasing extension, the PT-tibial cortex contact was lost in all subjects nearing 90° flexion. The contraction of the Q made the concave PT straight, grew the width of the underlying IPFP, and the apron of the IPFP moved distally within the IPB in all knee positions. A small amount of bursal fluid was present in all seven subjects., Conclusion: Q contraction makes the IPFP bulge anteriorly, on both sides of the PT, and distally into the IPB, with possible biomechanical implications. In full knee flexion, the PT contacted the tibia, confirming a fulcrum at this site., (Copyright © 2020. Published by Elsevier GmbH.)

To identify features associated with long-term persistent remission in rheumatoid arthritis (RA) patients on tapered biological disease-modifying antirheumatic drugs (bDMARD) (tap-bDMARD) therapy. We carried out a 40-month (m) extension follow-up study of 77 RA patients from a previous 12 m tap-bDMARD study. Disease activity was assessed at baseline and every 3 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy (SH) and synovial power Doppler signal (i.e., Doppler synovitis) was performed before starting the tap-bDMARD strategy by a rheumatologist blinded to clinical and laboratory data. At the 40 m mark, 44 (57.1%) patients failed the tap-bDMARD strategy, while 33 (42.9%) succeeded. Patients who presented a failed tap-bDMARD had significantly longer disease duration, a longer time from symptom onset to synthetic (s) DMARD start, longer duration of sDMARD treatment, a greater number of sDMARDs, and a higher baseline DAS28 and SDAI than patients with successful tap-bDMARD at 40 months. In logistic regression analysis, the presence of baseline Doppler synovitis, a DAS28 ≥ 2.2, and the presence of rheumatoid factor were identified as predictors of tap-bDMARD failure at 40 m. In those patients who succeed tap-bDMARD at 12 m, a smoking habit was significantly more frequently found in tap-bDMARD failures at 40 m. Our results showed that DAS28 and the presence of Doppler synovitis, RF and a smoking habit predicted long-term tap-bDMARD failure.

Objectives: The aim of this study was to investigate the relationship between serum infliximab (IFX) levels and changes of RF and ACPA levels in patients with rheumatoid arthritis (RA)., Methods: Enzyme-linked immunosorbent assays (ELISA) [Promonitor® IFX R1 (version 2) (Progenika Biopharma, Spain)] were used to measure drug levels and antidrug-antibodies (ADAb) in IFX RA-treated patients (n=19). Disease activity was assessed using DAS28. IgM rheumatoid factor (RF) and IgM, IgA and IgG anti-cyclic citrullinated peptide (ACPA) were determined through ELISA., Results: A significant decrease in RF (p=0.01), ACPA IgG (p=0.007), IgM (p=0.01) and IgA (p=0.03) was observed in patients presenting adequate levels of serum IFX. No significant changes to RF or ACPA were observed in patients with undetectable IFX., Conclusions: Data from this study support the hypothesis that the anti-TNF antagonist IFX downregulates autoantibody levels in RA patients when IFX levels are detectable. Larger-scale studies need to be performed to establish RF and ACPA presence as therapeutic response predictive factors.

This cross-sectional observational study aimed to explore the relationship between B cell count and ultrasound (US)-detected synovitis, in patients with rheumatoid arthritis treated with rituximab. Thirty-seven consecutive RA patients treated with RTX were recruited for the study. The patients underwent clinical [i.e., Disease Activity Score 28 joints (DAS28)], laboratory, and US assessment of 12 joints. Each joint was semiquantitatively (0-3) scored on B-mode and power Doppler mode. The scores were summed, and a global index was created for BM (BMS) and PD scores (PDI) synovitis. BM subclinical synovitis was evident in all patients, with PD synovial signal detected in 16 patients (43.2 %). No correlation was found between DAS28 and US scores. B cells were detected in 27 (72.9 %) patients, but there was no association in the mean B cell count and disease activity as measured by DAS28 (DAS28 < 2.6 = 34.53, DAS28 > 2.6 = 49.45, p = 0.52) and PDI score (PDI < 1 = 49.48, PDI > 1 = 35.44, p = 0.54). There was no correlation between the B cell count and DAS28, BMS, and PDI (r = 0.020, p = 0.907; r = -0.151, p = 0.371; r = -0.099, p = 0.558, respectively). In RTX-treated RA patients, no relationship could be established between US-detected synovitis and peripheral blood B cell count.

The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0-3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist-MCP-ankle-MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist-hand-ankle-MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.

Objective: To investigate the predictive value of synovitis detected by Doppler US in relation to failed tapering of biologic therapy (BT) in RA patients in sustained clinical remission., Methods: A total of 77 RA patients (52 women, 25 men) in sustained clinical remission, treated with a stable dosage of BT were prospectively recruited. BT was tapered according to an agreed strategy implemented in clinical practice (i.e. increasing the interval between doses for s.c. BT and reducing the dose for i.v. BT). BT tapering failure was assessed at 6 and 12 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy and synovial power Doppler signal (i.e. Doppler synovitis) was performed at baseline by a rheumatologist blinded to clinical and laboratory data. Hand and foot radiographs were obtained at baseline and at 12-month follow-up., Results: Of the 77 patients, 46 (59.7%) were on s.c. BT and 31 (40.3%) on i.v. BT. At 12 months, 35 patients (45.5%) presented BT tapering failure, 23 of them (29.9% of all patients) in the first 6 months of BT tapering. In logistic regression analysis, the baseline DAS28 and the global score of Doppler synovitis were identified as independent predictors of BT tapering failure at 12 and 6 months. The presence of Doppler synovitis was the strongest predictor for BT tapering failure. No patient showed radiographic progression., Conclusion: Our results suggest that the presence of Doppler-detected synovitis may predict BT tapering failure in RA patients in sustained clinical remission., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

There are various immunosorbent assays which can be used to determine infliximab (IFX) levels. Results vary between assays complicating reliability in everyday clinical practice. The aim of this study was to determine whether quantitative or qualitative assay data prove more accurate in the assessment of infliximab levels in AS patients. We analyzed 40 serum samples, taken prior to infusion, from AS patients who had been undergoing IFX therapy as a first-line of biological treatment for more than a year. IFX levels and IFX-anti-drug antibodies (ADA) were measured using two different ELISA assays [Promonitor IFX R1 and R2 (version 1), Promonitor IFX and anti-IFX (version 2) (Progenika Biopharma, Spain)] strictly following the manufacturer's guidelines. Cohen's unweighted kappa and the intraclass correlation coefficient determined qualitative and quantitative agreement for serum levels in version 1 and version 2. Bland-Altman plots were drawn to compare both assays. The comparison of data measuring IFX levels for version 1 and version 2 resulted in questionable quantitative agreement (ICC 0.659; 95% CI 0.317-0.830) and moderate qualitative agreement (κ 0.607; 95% CI 0.387-0.879) owing to systematically higher values in version 2 than version 1. Version 2 consistently detected higher levels of infliximab, particularly when analyzed in a quantitative context. Further research is needed to synchronize cutoff levels between essays and diseases so therapeutic drug ranges can be established.

The primary objective of this study was to describe and compare clinical and musculoskeletal (MS) ultrasound (US) features between psoriatic arthritis (PsA) patients treated with full and tapered dosage of biologic (b) disease-modified antirheumatic drugs (DMARDs). The secondary objective was to compare clinical and MSUS features between PsA patients treated with bDMARDs with and without concomitant synthetic (s) DMARDs. We evaluated 102 patients with PsA treated with bDMARDs. The bDMARD dosage tapering had been made in patients with a maintained remission or minimal disease activity (MDA) according to their attending rheumatologist and with the patient acceptance. The bDMARD tapering consisted of the following: increase the interval between doses for subcutaneous bDMARDs or reduction of the dose for intravenous bDMARDs. The clinical evaluation consisted of a dermatologic and rheumatologic assessment of disease activity. The presence of B-mode and Doppler synovitis, tenosynovitis, enthesopathy, and paratenonitis was investigated by a rheumatologist blinded to drug dosage, clinical assessments, and laboratory results. Seventy-four (72.5 %) patients received full dosage of bDMARDs and 28 (27.5 %) received tapered dosage. The duration with biologic therapy and with current biologic therapy was significantly higher in patients with tapered dosages (p = 0.008 and p = 0.001, respectively). We found no significant differences between clinical, laboratory, and US variables, both for BM and CD between patients with full and tapered dosage and between patients with and without concomitant sDMARD. Clinical assessment, MSUS variables, and MDA status are similar in patients receiving full and tapered dosage of bDMARDs.

Objective: The objective of this study was to compare disease activity assessed by the patient, the physician and musculoskeletal US in patients with RA in clinical remission., Methods: We evaluated 69 patients with RA in clinical remission according to their attending rheumatologist. Tenderness and swelling in 28 joints were blindly assessed by patients and physicians. The presence of B-mode and Doppler synovitis was blindly investigated in the above joints. The DAS28 and Simplified Disease Activity Index (SDAI) were calculated., Results: The percentage of patients in remission according to the self-derived DAS28 (26.1%) was significantly less than that according to the physician-derived DAS28 (52.2%) (P < 0.0005). There was no significant difference in the percentage of patients in remission according to the self-derived SDAI (14.5%) and the physician-derived SDAI (11.6%) (P = 0.172). We found moderate agreement between the patient-derived and physician-derived DAS28 and SDAI [intraclass correlation coefficient (ICC) = 0.620 and ICC = 0.678, respectively]. Agreement between patient and physician was better for the tender joint count (TJC; ICC = 0.509) than for the swollen joint count (SJC; ICC = 0.279). The mean (S.D.) count for B-mode synovitis [4.09 (3.25)] was significantly greater than the SJC assessed by both the patient and physician [2 (3.71) and 1.42 (2.03), respectively] (P < 0.0005 and P = 0.033, respectively). We found moderate agreement between the physician-assessed SJC and the joint count for Doppler synovitis (ICC = 0.528)., Conclusion: Patient-assessed and physician-assessed overall RA activity showed acceptable agreement. Patient self-assessment overestimated disease activity determined by the DAS28. At the patient level, physician-assessed joint swelling showed an acceptable concordance with Doppler US synovitis.

Objective: Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are related chronic autoimmune diseases of complex aetiology in which the interferon (IFN) pathway plays a key role. Recent studies have reported an association between IRF7 and SLE which confers a risk to autoantibody production. A study was undertaken to investigate whether the IRF7 genomic region is also involved in susceptibility to SSc and the main clinical features., Methods: Two case-control sets of Caucasian origin from the USA and Spain, comprising a total of 2316 cases of SSc and 2347 healthy controls, were included in the study. Five single nucleotide polymorphisms (SNPs) in the PHRF1-IRF7-CDHR5 locus were genotyped using TaqMan allelic discrimination technology. A meta-analysis was performed to test the overall effect of these genetic variants on SSc., Results: Four out of five analysed SNPs were significantly associated with the presence of anticentromere autoantibodies (ACA) in the patients with SSc in the combined analysis (rs1131665: p(FDR)=6.14 × 10(-4), OR=0.78; rs4963128: p(FDR)=6.14 × 10(-4), OR=0.79; rs702966: p(FDR)=3.83 × 10(-3), OR=0.82; and rs2246614: p(FDR)=3.83 × 10(-3), OR=0.83). Significant p values were also obtained when the disease was tested globally; however, the statistical significance was lost when the ACA-positive patients were excluded from the study, suggesting that these associations rely on ACA positivity. Conditional logistic regression and allelic combination analyses suggested that the functional IRF7 SNP rs1131665 is the most likely causal variant., Conclusions: The results show that variation in the IRF7 genomic region is associated with the presence of ACA in patients with SSc, supporting other evidence that this locus represents a common risk factor for autoantibody production in autoimmune diseases.