Wolfgang A. Schmidt

Evaluation of a novel 7‐joint ultrasound score in daily rheumatologic practice: A pilot project

OBJECTIVE To introduce a new standardized ultrasound score based on 7 joints of the clinically dominant hand and foot (German US7 score) implemented in daily rheumatologic practice. METHODS The ultrasound score included the following joints of the clinically dominant hand and foot: wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints. Synovitis and synovial/tenosynovial vascularity were scored semiquantitatively (grade 0-3) by gray-scale (GS) and power Doppler (PD) ultrasound. Tenosynovitis and erosions were scored for presence. The scoring range was 0-27 for GS synovitis, 0-39 for PD synovitis, 0-7 for GS tenosynovitis, 0-21 for PD tenosynovitis, and 0-14 for erosions. Patients with arthritis were examined at baseline and after the start or change of disease-modifying antirheumatic drug (DMARD) and/or tumor necrosis factor alpha (TNFalpha) inhibitor therapy 3 and 6 months later. C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, anti-cyclic citrullinated peptide, Disease Activity Score in 28 joints (DAS28), and radiographs of the hands and feet were performed. RESULTS One hundred twenty patients (76% women) with rheumatoid arthritis (91%) and psoriatic arthritis (9%) were enrolled. In 52 cases (43%), erosions were seen in radiography at baseline. Patients received DMARDs (41%), DMARDs plus TNFalpha inhibitors (41%), or TNFalpha inhibitor monotherapy (18%). At baseline, the mean DAS28 was 5.0 and the synovitis scores were 8.1 in GS ultrasound and 3.3 in PD ultrasound. After 6 months of therapy, the DAS28 significantly decreased to 3.6 (Delta = 1.4), and the GS and PD ultrasound scores significantly decreased to 5.5 (-32%) and 2.0 (-39%), respectively. CONCLUSION The German US7 score is a viable tool for examining patients with arthritis in daily rheumatologic practice because it significantly reflects therapeutic response.

2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

The objective of this study was to develop EULAR/ACR classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of RF and/or ACPA (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness>45 minutes, elevated CRP and/or ESR and new hip pain. These criteria are not meant for diagnostic purposes.

EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis

Objective To develop evidence-based recommendations on the use of imaging of the joints in the clinical management of rheumatoid arthritis (RA). Methods The task force comprised an expert group of rheumatologists, radiologists, methodologists and experienced rheumatology practitioners from 13 countries. Thirteen key questions on the role of imaging in RA were generated using a process of discussion and consensus. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, dual-emission x-ray absorptiometry, digital x-ray radiogrammetry, scintigraphy and positron emission tomography. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. The experts used the evidence obtained from the relevant studies to develop a set of 10 recommendations. The strength of recommendation was assessed using a visual analogue scale. Results A total of 6888 references was identified from the search process, from which 199 studies were included in the systematic review. Ten recommendations were produced encompassing the role of imaging in making a diagnosis of RA, detecting inflammation and damage, predicting outcome and response to treatment, monitoring disease activity, progression and remission. The strength of recommendation for each proposition varied according to both the research evidence and expert opinion. Conclusions Ten key recommendations for the role of imaging in the management of RA were developed using research-based evidence and expert opinion.

Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR “Train the trainers” course

Objective: To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging “gold standard”. Methods: The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. Results: Taking an agreement in US examination of 10 out of 14 experts into account, the overall κ for all examined joints was 0.76. Calculations for each joint region showed high κ values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). κ Values for bone lesions, bursitis, and tendon tears were high (κ = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). Conclusion: Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US.

Interobserver reliability in musculoskeletal ultrasonography: results from a “Teach the Teachers” rheumatologist course

Objective: To assess the interobserver reliability of the main periarticular and intra-articular ultrasonographic pathologies and to establish the principal disagreements on scanning technique and diagnostic criteria between a group of experts in musculoskeletal ultrasonography. Methods: The shoulder, wrist/hand, ankle/foot, or knee of 24 patients with rheumatic diseases were evaluated by 23 musculoskeletal ultrasound experts from different European countries randomly assigned to six groups. The participants did not reach consensus on scanning method or diagnostic criteria before the investigation. They were unaware of the patients’ clinical and imaging data. The experts from each group undertook a blinded ultrasound examination of the four anatomical regions. The ultrasound investigation included the presence/absence of joint effusion/synovitis, bony cortex abnormalities, tenosynovitis, tendon lesions, bursitis, and power Doppler signal. Afterwards they compared the ultrasound findings and re-examined the patients together while discussing their results. Results: Overall agreements were 91% for joint effusion/synovitis and tendon lesions, 87% for cortical abnormalities, 84% for tenosynovitis, 83.5% for bursitis, and 83% for power Doppler signal; κ values were good for the wrist/hand and knee (0.61 and 0.60) and fair for the shoulder and ankle/foot (0.50 and 0.54). The principal differences in scanning method and diagnostic criteria between experts were related to dynamic examination, definition of tendon lesions, and pathological v physiological fluid within joints, tendon sheaths, and bursae. Conclusions: Musculoskeletal ultrasound has a moderate to good interobserver reliability. Further consensus on standardisation of scanning technique and diagnostic criteria is necessary to improve musculoskeletal ultrasonography reproducibility.

Imaging for large-vessel vasculitis

Purpose of reviewUltrasonography, MRI, and PET are increasingly studied in large-vessel vasculitis. They have broadened our knowledge on these disorders and have a place in the diagnostic approach of these patients. Recent findingsTemporal artery ultrasonography can be used to guide the surgeon to that artery segment with the clearest ‘halo’ sign to perform a biopsy, or in experienced hands can even replace biopsy. The distal subclavian, axillary, and brachial arteries can also be examined. High-resolution MRI depicts superficial cranial and extracranial involvement patterns in giant cell arteritis (GCA). Contrast enhancement is prominent in active inflammation and decreases under successful steroid therapy. Presence of aortic complications such as aneurysm or dissection can be ruled out within the same investigation. Large thoracic vessel FDG-uptake is seen in the majority of patients with GCA, especially at the subclavian arteries and the aorta. FDG-PET cannot predict which patients are bound to relapse, and once steroids are started, interpretation is hazardous, which makes its role in follow-up uncertain. Increased thoracic aortic FDG-uptake at diagnosis of GCA may be a bad prognostic factor for later aortic dilatation. In patients with isolated polymyalgia rheumatica – who have less intense vascular FDG uptake – symptoms are caused by inflammation around the shoulders, hips, and spine. SummaryUltrasonography, MRI, and PET remain promising techniques in the scientific and clinical approach of large-vessel vasculitis.

Use of ultrasonography and positron emission tomography in the diagnosis and assessment of large-vessel vasculitis.

Purpose of reviewUltrasonography and positron emission tomography have been increasingly studied and, in part, introduced in clinical practice to diagnose large-vessel vasculitides, such as temporal arteritis, Takayasu arteritis, large-vessel giant cell arteritis, and isolated aortitis. Recent findingsUltrasonography reveals characteristic homogenous, concentric wall thickening in vasculitis, often combined with stenoses and, less frequently, with acute occlusions. Thirteen studies describe sensitivities of 40 to 100% (median, 86%) for temporal artery vessel wall edema compared with histology, and of 35 to 86% (median, 70%) compared with clinical diagnosis. If wall edema, stenoses, and occlusions are included, sensitivities increase to 91 to 100% (median, 95%) compared with histology, and to 83 to 100% (median, 88%) compared with clinical diagnosis. Specificities for wall edema are 68 to 100% (median, 93%) compared with histology, and 78 to 100% (median, 97%) compared with clinical diagnosis. One should be aware of large-vessel giant cell arteritis in all patients with temporal arteritis and polymyalgia rheumatica. Ultrasonography reveals characteristic wall thickening, particularly of the distal subclavian, axillary, and proximal brachial arteries. Findings in Takayasu arteritis are similar, but the vessel wall swelling is usually brighter. Positron emission tomography reveals vasculitis in arteries with a diameter of more than 4 mm. Ultrasonography and positron emission tomography agreed completely in the anatomic distribution of changes in patients with large-vessel giant cell arteritis. It reveals asymptomatic large-vessel vasculitis in giant cell arteritis and Takayasu arteritis. Positron emission tomography is not suitable for the assessment of temporal arteries. SummaryUltrasonography and positron emission tomography are new, promising techniques to assess large-vessel vasculitides.

Detection of Chlamydia pneumoniae in giant cell vasculitis and correlation with the topographic arrangement of tissue-infiltrating dendritic cells

OBJECTIVE Recent studies suggest that giant cell arteritis (GCA) may be an antigen-driven disease. Since Chlamydia pneumoniae has been identified in arterial vessel walls, it was hypothesized that this organism might be associated with GCA. METHODS Fourteen paraffin-embedded temporal artery biopsy specimens from 9 patients with GCA were examined by immunohistochemistry and by polymerase chain reaction (PCR) for the presence of C pneumoniae; for 5 patients, specimens were available from both the left and right arteries. Four temporal artery specimens from 3 patients with polymyalgia rheumatica (PMR) and 9 temporal artery specimens from 5 patients without GCA or PMR served as controls. RESULTS C pneumoniae was detected by both immunohistochemistry and PCR in 6 GCA patient samples. One GCA patient sample was immunopositive only; another was PCR positive only. Thus, C pneumoniae was found in 8 of 9 GCA patients. One of 4 control samples from the PMR patients was immunopositive, but PCR negative, for C pneumoniae. The C pneumoniae-positive PMR patient also had respiratory symptoms. The remaining 9 control samples were negative for C pneumoniae by both immunohistochemistry and PCR. Immunohistochemistry showed that bacteria predominate in the adventitial layer of temporal arteries, in granulomatous infiltrates. Dendritic cells were examined by immunohistochemistry for their presence and localization in consecutive temporal artery specimens, and showed a strong topographic relationship with C pneumoniae. Like the bacterium, dendritic cells predominate in the adventitial layer of the arteries. CONCLUSION C pneumoniae was found in temporal artery specimens from most GCA patients, in 1 specimen from a PMR patient, and in no other control specimens; thus, it may play a role in the pathogenesis of the disease. Dendritic cells may represent the antigen-presenting cells in this situation.

Validation of a predictive model for identifying an increased risk for thromboembolism in children with acute lymphoblastic leukemia: results of a multicenter cohort study

Among risk factors for developing thromboembolism (VTE) in children with acute lymphoblastic leukemia were Escherichia coli asparaginase, concomitant steroid use, presence of central venous lines, and thrombophilic abnormalities. Developing a predictive model for determining children at increased risk would be beneficial in targeting interventional studies to high-risk groups (HRGs). Predictive variables were incorporated into a risk assessment model, which was evaluated in 456 children and then validated in 339 patients. VTE risk by score was no greater than 2.5 for low-risk group (LRG) and greater than 2.5 for HRG. VTE rates at 3.5 months (validation cohorts) were 2.5% in LRG and 64.7% in HRG. In multivariate analysis adjusted for age, duration of asparaginase administration, enoxaparin prophylaxis, and T-immunophenotype, the HRG was significantly associated with VTE compared with the LRG (hazard/95% confidence interval [CI], 8.22/1.85-36.53). Model specificity was 96.2% and sensitivity was 63.2%. As secondary objective we investigated the use of enoxaparin for VTE prophylaxis in the HRG. HRG patients without enoxaparin prophylaxis showed a significantly reduced thrombosis-free survival compared with children on low-molecular-weight heparin (LMWH). On the basis of the high specificity, the model may identify children with leukemia at risk of VTE. LMWH may help prevent VTE in the HRG; this warrants assessment in larger cooperative clinical trials.

The OMERACT ultrasound task force - Status and perspectives

This article reports the most recent work of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Task Force, and highlights the future research priorities discussed at the OMERACT 10 meeting. Results of the following studies were presented: (1) intra- and interobserver reliability of ultrasound detecting and scoring synovitis in different joints of patients with rheumatoid arthritis (RA); (2) systematic review of previous ultrasound scoring systems of synovitis in RA; (3) enthesitis systematic review and Delphi definition exercise in spondyloarthritis enthesitis; (4) enthesitis intra- and interobserver reliability exercise; and (5) Delphi definition exercise in hand osteoarthritis, and reliability exercises. Study conclusions were discussed, and a future research agenda was approved, notably further validation of an OMERACT ultrasound global synovitis score (GLOSS) in RA, emphasizing the importance of testing feasibility, predictive value, and added value over standard clinical variables. Future research areas will include validating scoring systems for enthesitis and osteoarthritis, and testing the metric qualities of ultrasound for evaluating tenosynovitis and structural damage in RA.