Rusmir Husic

Disparity between ultrasound and clinical findings in psoriatic arthritis

Objective To investigate the association between psoriatic arthritis (PsA)-specific clinical composite scores and ultrasound-verified pathology as well as comparison of clinical and ultrasound definitions of remission. Methods We performed a prospective study on 70 consecutive PsA patients. Clinical assessments included components of Disease Activity Index for Psoriatic Arthritis (DAPSA) and the Composite Psoriatic Disease Activity Index (CPDAI). Minimal disease activity (MDA) and the following remission criteria were applied: CPDAI joint, entheses and dactylitis domains (CPDAI-JED)=0, DAPSA≤3.3, Booleans remission definition and physician-judged remission (rem-phys). B-mode and power Doppler (PD-) ultrasound findings were semiquantitatively scored at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses. Ultrasound remission and minimal ultrasound disease activity (MUDA) were defined as PD-score=0 and PD-score ≤1, respectively, at joints, peritendinous tissue, tendons and entheses. Results DAPSA but not CPDAI correlated with B-mode and PD-synovitis. Ultrasound signs of enthesitis, dactylitis, tenosynovitis and perisynovitis were not linked with clinical composites. Clinical remission or MDA was observed in 15.7% to 47.1% of PsA patients. Ultrasound remission and MUDA were present in 4.3% and 20.0% of patients, respectively. Joint and tendon-related PD-scores were higher in patients with active versus inactive disease according to CPDAI-JED, DAPSA, Booleans and rem-phys, whereas no difference was observed regarding enthesitis and perisynovitis. DAPSA≤3.3 (OR 3.9, p=0.049) and Booleans definition (OR 4.6, p=0.03) were more useful to predict MUDA than other remission criteria. Conclusions PsA-specific composite scores partially reflect ultrasound findings. DAPSA and Booleans remission definitions better identify MUDA patients than other clinical criteria.

Ultrasound for diagnosis of carpal tunnel syndrome: comparison of different methods to determine median nerve volume and value of power Doppler sonography

Objective To compare ultrasound measurement of median nerve cross-sectional area (CSA) at different anatomical landmarks and to assess the value of power Doppler signals within the median nerve for diagnosis of carpal tunnel syndrome (CTS). Methods A prospective study of 135 consecutive patients with suspected CTS undergoing two visits within 3 months. A final diagnosis of CTS was established by clinical and electrophysiological findings. CSA was sonographically measured at five different levels at forearm and wrist; and CSA wrist to forearm ratios or differences were calculated. Intraneural power Doppler signals were semiquantitatively graded. Diagnostic values of different ultrasound methods were compared by receiver operating characteristic curves using SPSS. Results CTS was diagnosed in 111 (45.5%) wrists; 84 (34.4%) had no CTS and 49 (20.1%) were possible CTS cases. Diagnostic values were comparable for all sonographic methods to determine median nerve swelling, with area under the curves ranging from 0.75 to 0.85. Thresholds of 9.8 and 13.8 mm2 for the largest CSA of the median nerve yielded a sensitivity of 92% and a specificity of 92%. A power Doppler score of 2 or greater had a specificity of 90% for the diagnosis of CTS. Sonographic median nerve volumetry revealed a good reliability with an intraclass correlation coefficient of 0.90 (95% CI 0.79 to 0.95). Conclusions Sonographic assessment of median nerve swelling and vascularity allows for a reliable diagnosis of CTS. Determination of CSA at its maximal shape offers an easily reproducible tool for CTS classification in daily clinical practice.

Ultrasound composite scores for the assessment of inflammatory and structural pathologies in Psoriatic Arthritis (PsASon-Score)

IntroductionThis study was performed to develop ultrasound composite scores for the assessment of inflammatory and structural lesions in Psoriatic Arthritis (PsA).MethodsWe performed a prospective study on 83 PsA patients undergoing two study visits scheduled 6 months apart. B-mode and Power Doppler (PD) findings were semi-quantitatively scored at 68 joints (evaluating synovia, perisynovial tissue, tendons and bone) and 14 entheses. We constructed bilateral and unilateral (focusing the dominant site) ultrasound composite scores selecting relevant sites by a hierarchical approach. We tested convergent construct validity, reliability and feasibility of inflammatory and structural elements of the scores as well as sensitivity to change for inflammatory items.ResultsThe bilateral score (termed PsASon22) included 22 joints (6 metacarpophalangeal joints (MCPs), 4 proximal interphalangeal joints (PIPs) of hands (H-PIPs), 2 metatarsophalangeal joints (MTPs), 4 distal interphalangeal joints (DIPs) of hands (H-DIPs), 2 DIPs of feet (F-DIPs), 4 large joints) and 4 entheses (bilateral assessment of lateral epicondyle and distal patellar tendon). The unilateral score (PsASon13) compromised 13 joints (2 MCPs, 3 H-PIPs, 1 PIP of feet (F-PIP), 2 MTPs, 1 H-DIP and 2 F-DIPs and 2 large joints) and 2 entheses (unilateral lateral epicondyle and distal patellar tendon). Both composite scores revealed a moderate to high sensitivity (bilateral composite score 43% to 100%, unilateral 36% to 100%) to detect inflammatory and structural lesions compared to the 68-joint/14-entheses score. The inflammatory and structural components of the composite scores correlated weakly with clinical markers of disease activity (corrcoeffs 0 to 0.40) and the health assessment questionnaire (HAQ, corrcoeffs 0 to 0.39), respectively. Patients with active disease achieving remission at follow-up yielded greater reductions of ultrasound inflammatory scores than those with stable clinical activity (Cohen’s d effect size ranging from 0 to 0.79). Inter-rater reliability of bi- and unilateral composite scores was moderate to good with ICCs ranging from 0.42 to 0.96 and from 0.36 to 0.71, respectively for inflammatory and structural sub-scores. The PsASon22 and PsASon13 required 16 to 26 and 9 to 13 minutes, respectively to be completed.ConclusionBoth new PsA ultrasound composite scores (PsASon22 and PsASon13) revealed sufficient convergent construct validity, sensitivity to change, reliability and feasibility.

Premature senescence of T-cell subsets in axial spondyloarthritis

Objective To investigate the possible occurrence of early thymic failure and premature senescence of naïve and memory T-cells in patients with axial spondyloarthritis (aSpA). Methods Prospective, cross-sectional study of consecutive patients with aSpA (n=51), rheumatoid arthritis (RA, n=51) and healthy controls (HCs, n=50). Demographic, clinical and laboratory parameters were collected in all patients and we isolated naïve (CD45RA+) and memory (CD45RO+) CD4+ and CD8+ T-cell subsets by MACS technology. T-cell receptor rearrangement excision circle (TREC) and telomere length were measured by real-time PCR. We used TRECs as a surrogate for thymus function and telomere length as an indicator of cellular senescence. Telomerase activity was analysed with the Telomeric Repeat Amplification Protocols. Results We observed a premature decline of thymic output in patients with aSpA and patients with RA compared with HCs as indicated by a reduction of TREC levels in naive T-cells (aSpA: age adjusted regression coefficient (regcoeff) for CD4+CD45RA+ T-cells −2.566, p=0.023; RA regcoeff=−2.844, p=0.008). Telomere length of all CD4+ and CD8+ T-cell subsets was reduced in young patients with aSpA compared with HCs, whereas data for patients with RA were comparable with HCs. Telomerase activity was inversely correlated with telomere length in HCs (correlation coefficient (corcoeff)=−0.532, p<0.001) but not in patients with aSpA (corcoeff=−0.056, p=0.697) and RA (corcoeff=−0.003, p=0.982). Conclusions Our data indicate an age-inappropriate shrinkage of thymic output, an inappropriate shortening of telomeres in young patients with aSpA and an impaired telomerase enzyme in patients with aSpA and RA.

Novel Senescent Regulatory T-Cell Subset with Impaired Suppressive Function in Rheumatoid Arthritis

Objective Premature senescence of lymphocytes is a hallmark of inflammatory rheumatic diseases such as rheumatoid arthritis (RA). Early T-cell aging affects conventional T-cells but is presumably not limited to this cell population; rather it might also occur in the regulatory T-cells (Tregs) compartment. In RA, Tregs fail to halt aberrant immune reactions and disease progression. Whether this is associated with early Treg senescence leading to phenotypic and functional changes of this subset is elusive so far. Methods Eighty-four RA patients and 75 healthy controls were prospectively enrolled into the study. Flow cytometry, magnetic-associated cell sorting, and cell culture experiments were performed for phenotypic and functional analyses of Treg subsets. T-cell receptor excision circle (TREC) levels and telomere lengths were determined using RT-PCR. Results In this paper, we describe the novel CD4+FoxP3+CD28− T-cell subset (CD28− Treg-like cells) in RA patients revealing features of both Tregs and senescent T-cells: Treg surface/intracellular markers such as CD25, CTLA-4, and PD-1 as well as FOXP3 were all expressed by CD28− Treg-like cells, and they yielded signs of premature senescence including reduced TREC levels and an accumulation of γH2AX. CD28− Treg-like could be generated in vitro by stimulation of (CD28+) Tregs with TNF-α. CD28− Treg-like cells insufficiently suppressed the proliferation of effector T-cells and yielded a pro-inflammatory cytokine profile. Conclusion In conclusion, we describe a novel T-cell subset with features of Tregs and senescent non-Tregs. These cells may be linked to an aberrant balance between regulatory and effector functions in RA.

Joint positions matter for ultrasound examination of RA patients-increased power Doppler signal in neutral versus flat position of hands.

Objective Position of joints might influence the result of US examination in patients with RA. The purpose of this work was to compare grey-scale (GS) and power Doppler (PWD) findings obtained in neutral vs flat position of hands. Methods A cross-sectional study of 42 RA patients with active disease. Two dimensional and 3D sonography of wrists and MCP joints were conducted in two different joint positions: neutral position, which is a slight flexion of the fingers with relaxed extensor muscles; and flat position, where all palm and volar sides of fingers touch the Table. Two dimensional GS synovitis (GSS) and PWD signals were scored semi-quantitatively (0-3). For 3D sonography, the percentage of PWD voxels within a region of interest was calculated. GSS was not quantified using 3D sonography. Results Compared with neutral position, 2D PWD signals disappeared in 28.3% of joints upon flattening. The median global 2D PWD score (sum of all PWD scores of an individual patient) decreased from 8 to 3 ( P < 0.001), and the global 3D PWD voxel score from 3.8 to 0.9 ( P < 0.001). The reduction of PWD scores was similar in all joints (2D: minus 50%, 3D: minus 66.4-80.1%). Inter- and intrareader agreement of PWD results was good (intraclass correlation coefficient: 0.75-0.82). Conclusion In RA, a neutral position of the hands is linked to a higher sensitivity of 2D and 3D sonography in detecting PWD signals at wrists and MCP joints, compared with a flat position. Standardization of the scanning procedure is essential for obtaining comparable US results in RA patients in trials and clinical routines.

The Value of Median Nerve Sonography as a Predictor for Short- and Long-Term Clinical Outcomes in Patients with Carpal Tunnel Syndrome: A Prospective Long-Term Follow-Up Study

Objectives To investigate the prognostic value of B-mode and Power Doppler (PD) ultrasound of the median nerve for the short- and long-term clinical outcomes of patients with carpal tunnel syndrome (CTS). Methods Prospective study of 135 patients with suspected CTS seen 3 times: at baseline, then at short-term (3 months) and long-term (15–36 months) follow-up. At baseline, the cross-sectional area (CSA) of the median nerve was measured with ultrasound at 4 levels on the forearm and wrist. PD signals were graded semi-quantitatively (0–3). Clinical outcomes were evaluated at each visit with the Boston Questionnaire (BQ) and the DASH Questionnaire, as well as visual analogue scales for the patient’s assessment of pain (painVAS) and physician’s global assessment (physVAS). The predictive values of baseline CSA and PD for clinical outcomes were determined with multivariate logistic regression models. Results Short-term and long-term follow-up data were available for 111 (82.2%) and 105 (77.8%) patients, respectively. There was a final diagnosis of CTS in 84 patients (125 wrists). Regression analysis revealed that the CSA, measured at the carpal tunnel inlet, predicted short-term clinical improvement according to BQ in CTS patients undergoing carpal tunnel surgery (OR 1.8, p = 0.05), but not in patients treated conservatively. Neither CSA nor PD assessments predicted short-term improvement of painVAS, physVAS or DASH, nor was any of the ultrasound parameters useful for the prediction of long-term clinical outcomes. Conclusions Ultrasound assessment of the median nerve at the carpal tunnel inlet may predict short-term clinical improvement in CTS patients undergoing carpal tunnel release, but long-term outcomes are unrelated to ultrasound findings.

Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis

Objective T-cells are critical players in the pathogenesis of osteoporosis in patients with rheumatoid arthritis (RA). Premature senescence of lymphocytes including the accumulation of senescent CD4+ T-cells is a hallmark feature of RA. Whether T-cell senescence is associated with bone loss in RA patients is elusive so far. Methods This includes a prospective study of consecutive patients with RA (n = 107), patients with primary osteopenia/-porosis (n = 75), and healthy individuals (n = 38). Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry scan. Flow cytometry, magnetic-associated cell sorting, and cell culture experiments were performed to analyze the pro-osteoclastic phenotype and the function of senescent CD4+CD28− T-cells. Results Patients with osteopenia/-porosis yielded a higher prevalence of senescent CD4+CD28− T-cells than individuals with normal BMD, in the RA, as well as in the non-RA cohort. Receptor activator of nuclear factor kappa-B ligand (RANKL) was expressed at higher levels on CD4+CD28− T-cells as compared to CD28+ T-cells. Stimulation with interleukin-15 led to an up-regulation of RANKL expression, particularly on CD28− T-cells. CD4+CD28− T-cells induced osteoclastogenesis more efficiently than CD28+ T-cells. Conclusion Our data indicate that senescent T-cells promote osteoclastogenesis more efficiently than conventional CD28+ T-cells, which might contribute to the pathogenesis of systemic bone loss in RA and primary osteoporosis.

Ultrasound verified inflammation and structural damage in patients with hereditary haemochromatosis-related arthropathy

BackgroundChronic arthropathy occurs in approximately two thirds of patients with hereditary haemochromatosis (HH). The aim was to study inflammatory and structural lesions in patients with HH with (HH-A) and without arthropathy (HH-WA) using ultrasonography.MethodsThis was a cross-sectional study of 26 patients with HH-A, 24 with HH-WA and 37 with hand osteoarthritis (HOA). Clinical examination was performed in 68 joints, and we retrieved data on hand function, pain and global disease activity (all using a visual analogue scale (VAS)), morning stiffness and ferritin levels. Standard x-ray and ultrasound were conducted in 36 joints (hands, hips, knees and ankles), and we graded grey scale synovitis (GSS), power Doppler ultrasound (PD), osteophytes, erosions, tenosynovitis and cartilage damage semi-quantitatively in accordance with prior publications.ResultsUltrasound revealed a high proportion of inflammatory changes in HH-A; GSS was found in 96.2% and PD signals in 80.8% of patients (median GSS score 9, PD score 2.5). The frequency of these findings was similar in HOA. Inflammation was also common in HH-WA, yielding GSS in 83.3% and PD signals in 50.0% of patients. Cartilage damage was most prominent in HH-A as compared to HH-WA and HOA (median scores 11.0, 2.5 and 2.0, respectively). The prevalence and extent of erosions and osteophytes were similar in all groups. None of the ultrasound scores was associated with pain or function; GSS, PD, osteophyte and cartilage scores correlated with x-ray-verified structural damage.ConclusionA high prevalence of ultrasound-verified inflammation and cartilage damage was found in HH-A, and to a lesser extent in HH-WA. These findings were associated with x-ray-verified damage but not with clinical scores of pain and function.

Empfehlungen der Österreichische Gesellschaft für Rheumatologie und Rehabilitation/Austrian Radiology-Rheumatology Initiative for Musculoskeletal Ultrasound zur Anwendung des Ultraschalls bei rheumatischen Erkrankungen in der klinischen Praxis

It is the current goal in rheumatology to diagnose and treat inflammatory rheumatic diseases early in order to avoid structural damage. Functional imaging methods such as musculoskeletal sonography are increasingly used to support the clinical diagnosis. To ascertain the quality of ultrasound assessments performed by rheumatologists in Austria, the Austrian Radiology-Rheumatology Initiative for Musculoskeletal Ultrasound (ARRIMUS) proposed recommendations for a training curriculum, technical standards for ultrasound equipment, minimum requirements for documentation, indications for sonography and the use of ultrasound for interventions. These recommendations have been endorsed by the Austrian Society of Rheumatology and should aid rheumatologists to perform high quality ultrasound assessment in clinical practice.ZusammenfassungDie Frühdiagnostik gewinnt in der Rheumatologie zunehmend an Bedeutung. Chronisch entzündliche Erkrankungen sollten möglichst vor dem Auftreten radiologisch sichtbarer Schäden diagnostiziert werden und so ist der Einsatz funktioneller bildgebender Methoden wie des Ultraschalls oftmals unverzichtbar.Zur Qualitätssicherung und -verbesserung der von Rheumatologen durchgeführten Ultraschalluntersuchungen wurden von der Austrian Radiology-Rheumatology Initiative for Musculoskeletal Ultrasound (ARRIMUS) Empfehlungen für die technische Ausstattung, Indikationen und Dokumentation der Ultraschall-Untersuchung, Zuhilfenahme des Ultraschalls bei Gelenkspunktion und -infiltration sowie ein Ausbildungscurriculum formuliert.Diese Empfehlungen wurden von der Österreichischen Gesellschaft für Rheumatologie und Rehabilitation (ÖGR) befürwortet und sollen als Grundlage zur Etablierung und Qualitätssicherung der Sonographie bei rheumatischen Erkrankungen in der klinischen Praxis dienen.SummaryIt is the current goal in rheumatology to diagnose and treat inflammatory rheumatic diseases early in order to avoid structural damage. Functional imaging methods such as musculoskeletal sonography are increasingly used to support the clinical diagnosis. To ascertain the quality of ultrasound assessments performed by rheumatologists in Austria, the Austrian Radiology-Rheumatology Initiative for Musculoskeletal Ultrasound (ARRIMUS) proposed recommendations for a training curriculum, technical standards for ultrasound equipment, minimum requirements for documentation, indications for sonography and the use of ultrasound for interventions. These recommendations have been endorsed by the Austrian Society of Rheumatology and should aid rheumatologists to perform high quality ultrasound assessment in clinical practice.