[Recommendations for defining giant cell arteritis fast-track clinics]. / Empfehlungen zur Definition von Riesenzellarteriitis-Fast-Track-Kliniken.

An expert committee recommends defining fast-track clinics (FTC) for the acute diagnostics of giant cell arteritis (GCA) as follows: low-threshold, easy and prompt reachability at least on weekdays, scheduling appointments ideally within 24 h, examination by a specialist with GCA expertise, ≥ 2 experts per FTC, ≥ 50 patients with suspected GCA per year, sonologists with ≥ 300 (≥ 50) temporal and axillary artery examinations, adherence to standard operating procedures, availability of an ≥ 18 (≥ 15) MHz and a lower frequency linear ultrasound probe and collaboration with partners for fast performance of neurological and ophthalmological examinations, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT, possibly CT) and for temporal artery biopsy.

Association of Serum Soluble Transferrin Receptor Concentration With Markers of Inflammation: Analysis of 1001 Patients From a Tertiary Rheumatology Center.

OBJECTIVE: Soluble transferrin receptor (sTfR) is considered to be a useful biomarker for the diagnosis of iron deficiency, especially in the setting of inflammation, as it is thought to not be affected by inflammation. We analyzed the relationship between sTfR levels and inflammatory markers in patients with known or suspected inflammatory rheumatic disease (IRD). METHODS: Blood samples of 1001 patients with known or suspected IRD referred to a tertiary rheumatology center were analyzed. Study participants were classified as patients with active IRD and patients with inactive IRD or without IRD. Correlation analyses were used to explore the relationship between sTfR levels and inflammatory markers (ie, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]). We applied multiple linear regression analysis to evaluate the predictive value of CRP levels for sTfR concentrations after adjustment for potential confounding factors. RESULTS: There were positive correlations between inflammatory markers (CRP, ESR) and serum sTfR levels (ρ 0.44, ρ 0.43, respectively; P < 0.001), exceeding the strength of correlation between inflammatory markers and the acute phase reactant ferritin (ρ 0.30, ρ 0.23, respectively; P < 0.001). Patients with active IRD demonstrated higher serum sTfR levels compared to patients with inactive or without IRD (mean 3.99 [SD 1.69] mg/L vs 3.31 [SD 1.57] mg/L; P < 0.001). After adjustment for potential confounding factors, CRP levels are predictive for serum sTfR concentrations (P < 0.001). CONCLUSION: The study provides evidence against the concept that sTfR is a biomarker not affected by inflammation.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

[Ultrasound-targeted joint puncture in rheumatology]. / Ultraschallgezielte Gelenkpunktion in der Rheumatologie.

Joint punctures not only have a long tradition but are also an essential component in the diagnostic differentiation of various joint diseases. In addition, therapeutic injections are an essential component of an individual targeted treatment strategy in a disease-modifying antirheumatic drug (DMARD)-based treat-to-target concept. This article aims to convey to the reader the ultrasound-targeted joint puncture techniques in text and with many video clips that can be downloaded. This article therefore steps away from the conventional two-dimensional demonstration of anatomy-oriented puncture techniques and elucidates the diagnostic and therapeutic potency of ultrasound-targeted techniques in the daily routine. Furthermore, special importance is given to a sterile working technique, puncture material and synovial analysis.

Usefulness of Soluble Transferrin Receptor in the Diagnosis of Iron Deficiency Anemia in Rheumatoid Arthritis Patients in Clinical Practice.

Aim: We analyzed the added value of sTfR measurement in routine clinical practice to standard parameters (SP) of iron deficiency in the detection of iron deficiency anemia (IDA) in patients with rheumatoid arthritis (RA). Methods: Blood samples from 116 patients with RA were analyzed in a prospective study. Based on biochemical parameters, patients were classified as having IDA, anemia of chronic disease (ACD), IDA with concomitant ACD (ACD/IDA), or "other anemia." Sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of sTfR and SP of iron status alone and in combination were calculated for the diagnosis of IDA in general, i.e., IDA or ACD/IDA. Results: In the whole sample, with regard to the diagnosis of iron deficiency (IDA or ACD/IDA), sTfR had a higher sensitivity compared both to the combined use of SP and to the combination of SP with sTfR (80.9% versus 66.7/54.8%). Specificity, PPV and NPV did not differ substantially. When patients were stratified in groups with high (CRP levels above the median, i.e., 24.1 mg/l) and low (CRP levels less or equal to the median) inflammation, the diagnostic superiority of sTfR was restricted to patients with high inflammation. In this group, the diagnostic performance of sTfR was superior both to the combined use of SP and the combination of SP with sTfR with higher sensitivity (100% versus 52.4%) and NPV (100% versus 77.7/76.7%) and comparable specificity and PPV. Conclusion: For the detection of iron depletion (IDA or ACD/IDA) in anemic RA patients, sTfR is superior to SP of iron deficiency only in highly inflammatory states.

The EFSUMB Guidelines and Recommendations for Musculoskeletal Ultrasound - Part II: Joint Pathologies, Pediatric Applications, and Guided Procedures.

The second part of the Guidelines and Recommendations for Musculoskeletal Ultrasound (MSUS), produced under the auspices of EFSUMB, following the same methodology as for Part 1, provides information and recommendations on the use of this imaging modality for joint pathology, pediatric applications, and musculoskeletal ultrasound-guided procedures. Clinical application, practical points, limitations, and artifacts are described and discussed for every joint or procedure. The document is intended to guide clinical users in their daily practice.

EULAR points to consider for the use of imaging to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs).

OBJECTIVES: To develop evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: European Alliance of Associations for Rheumatology (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound (US), fluoroscopy, MRI, CT and fusion imaging to guide interventional procedures. Based on evidence and expert opinion, the task force (25 participants consisting of physicians, healthcare professionals and patients from 11 countries) developed PtC, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: A total of three overarching principles and six specific PtC were formulated. The task force recommends preference of imaging over palpation to guide targeted interventional procedures at peripheral joints, periarticular musculoskeletal structures, nerves and the spine. While US is the favoured imaging technique for peripheral joints and nerves, the choice of the imaging method for the spine and sacroiliac joints has to be individualised according to the target, procedure, expertise, availability and radiation exposure. All imaging guided interventions should be performed by a trained specialist using appropriate operational procedures, settings and assistance by technical personnel. CONCLUSION: These are the first EULAR PtC to provide guidance on the role of imaging to guide interventional procedures in patients with RMDs.

The EFSUMB Guidelines and Recommendations for Musculoskeletal Ultrasound - Part I: Extraarticular Pathologies.

The first part of the guidelines and recommendations for musculoskeletal ultrasound, produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), provides information about the use of musculoskeletal ultrasound for assessing extraarticular structures (muscles, tendons, entheses, ligaments, bones, bursae, fasciae, nerves, skin, subcutaneous tissues, and nails) and their pathologies. Clinical applications, practical points, limitations, and artifacts are described and discussed for every structure. After an extensive literature review, the recommendations have been developed according to the Oxford Centre for Evidence-based Medicine and GRADE criteria and the consensus level was established through a Delphi process. The document is intended to guide clinical users in their daily practice.

Etablierung und Validierung eines didaktischen muskuloskelettalen Ultraschallkurses für Dermatologen unter Verwendung eines innovativen Hand-Ultraschallsystems - die MUDE-Studie (Muskuloskelettaler Ultraschall für Dermatologen).

HINTERGRUND: Der muskuloskelettale Ultraschall (MSUS) schmerzhafter Gelenke spielt bei der Früherkennung der Arthritis, wie zum Beispiel der Psoriasisarthritis, eine wichtige Rolle. Pathologische Befunde können bei der klinischen Untersuchung übersehen werden, insbesondere wenn sie von Ärzten durchgeführt werden, die nicht in der Durchführung geschult sind. Das Ziel dieser Studie war die Untersuchung eines Pilot-MSUS-Kurses anhand des MUDE-Protokolls, welches speziell für Dermatologen entwickelt wurde. METHODIK: Um den Grad der MSUS-Expertise der Teilnehmer zu ermitteln, wurde vor dem Kurs eine Umfrage mittels SurveyMonkey® durchgeführt. Das Kurskonzept umfasste nur die wichtigsten Ultraschallschnitte aller Gelenke und konzentrierte sich auf die Erkennung von Gelenkergüssen und Hyperperfusion der Synovia. Der Kurs bestand aus drei Modulen und wurde über sechs Monate durchgeführt. Das tragbare Butterfly IQ® System in Kombination mit einem Apple iPad wurde allen Teilnehmern zur Verfügung gestellt, um das Üben zwischen den Kursen zu ermöglichen. Die abschließende Lehrevaluation wurde als objective structured clinical examination (OSCE) durchgeführt. ERGEBNISSE: Zwölf Dermatologen nahmen teil. Die Umfrage ergab keine Vorkenntnisse des MSUS. Die Gesamtpunktzahl aller Teilnehmer in der OSCE betrug 21,86 (87,44 %) von insgesamt 25 Punkten, was der Schulnote "gut" entsprach. SCHLUSSFOLGERUNG: Das innovative Lehrkonzept MUDE eignet sich somit, unabhängig von Vorkenntnissen, in besonderer Weise für die Ausbildung von Dermatologen im MSUS.

Establishment and validation of a didactic musculoskeletal ultrasound course for dermatologists using an innovative handheld ultrasound system - the MUDE study (Musculoskeletal Ultrasound in Dermatology).

BACKGROUND: In the early detection of arthritis, such as psoriatic arthritis, musculoskeletal ultrasound (MSUS) of painful joints plays an important role in diagnosis. Pathological findings can be missed during clinical examination, especially if conducted by physicians who are not trained. The objective of this study was to examine a pilot MSUS course designed specifically for dermatologists, the MUDE protocol. METHODS: To assess the degree of MSUS expertise of the participants, a questionnaire using SurveyMonkey® was completed before the course. The course concept covered only the most important ultrasound sections of all joints and focused on the detection of joint effusion and hyperperfusion. The course consisted of three modules and was carried out over six months. The portable Butterfly IQ® system in combination with an Apple iPad was provided to enable practice between the courses. The final teaching evaluation was carried out as an objective structured clinical examination (OSCE). RESULTS: Twelve dermatologists participated. The survey revealed no prior knowledge of MSUS. The overall score of all participants in the OSCE was 21.86 (87.44 %) out of a total of 25 points, which corresponded to the school grade good. CONCLUSION: The innovative MUDE protocol is thus particularly suitable for the training of dermatologists in MSUS, irrespective of prior knowledge.

OMERACT definition and reliability assessment of chronic ultrasound lesions of the axillary artery in giant cell arteritis.

OBJECTIVES: To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. METHODS: A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. RESULTS: The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. CONCLUSION: The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.

[Sports and exercise therapy in inflammatory rheumatic diseases]. / Sport und Bewegungstherapie bei entzündlich rheumatischen Erkrankungen.

Physical therapy has always been a pillar of the treatment of inflammatory rheumatic diseases in addition to targeted drug treatment; nevertheless, it is only established in the treatment guidelines for a few diseases. Within the last two decades the discovery of myokines has uncovered the physiological correlations of the anti-inflammatory effect of physical activity. For rheumatoid arthritis and spondylarthritis, several randomized controlled trials provide sufficient evidence to make well-founded recommendations. For connective tissue diseases (CTD) the data situation is clearly sparser but nevertheless shows that the positive effects of physical activity prevail. In the following article the authors present the most important clinical studies on sport and inflammatory rheumatic diseases and from these derive possible therapeutic recommendations.

Prevalence of Elbow Joint Arthritis and Enthesitis in Rheumatoid Arthritis.

OBJECTIVES: The prevalence of elbow joint arthritis in rheumatoid arthritis (RA) assessed by ultrasound has not yet been investigated. METHODS: We investigated 102 patients with RA and 50 patients without rheumatological disease. Both elbow joints were examined by ultrasound for effusion, hypervascularization, and enthesitis. A clinical examination was performed, and Disease Activity Score in 28 joints (DAS28), and visual analog scale for pain (VASp) were recorded. Arthritis was defined as joint effusion (≥grade II) and synovial hyperperfusion. RESULTS: The RA cohort versus the control group displayed a joint effusion in 54.9% vs. 6.9%, a hypervascularization in 6.8% vs. 0%. Arthritis was detected in 36 RA patients (35.29%) and no one in the control group. Four (3.8%) RA patients and one (1%) control displayed enthesitis. The RA cohort showed a significant correlation between movement restriction and joint effusion (p-value = 0.001) as well as DAS28 (p-value = 0.02) and between DAS28 and ultrasound detected arthritis (p-value = 0.022). In an overall analysis, a highly significant correlation of VASp with movement restriction (MR) (p-value ≤ 0.001), the presence of joint effusion (p-value ≤ 0.001), and the diagnosis of RA (p-value ≤ 0.001) were observed. Interrater analysis of ultrasound imaging showed good agreement with Cohen's kappa of 0.896. CONCLUSION: The prevalence of elbow arthritis in RA seems to be high, with 35.29%. Movement restriction is a good indicator, but not in all RA patients (32 vs. 70 patients without MR) compared to the control group (5 vs. 45 patients without MR). Reported pain correlates with joint effusion and MR (p-value ≤ 0.001).

Association between autoantibody level and disease activity in rheumatoid arthritis is dependent on baseline inflammation.

OBJECTIVES: It is still controversial whether autoantibody (AAb) serum levels have a value for response monitoring in rheumatoid arthritis (RA). Therefore, we retrospectively investigated a real-life outpatient RA cohort to determine which factors are associated with change in serum AAb levels and RA disease activity. The primary goal of the study was to determine predictors for changes in DAS28 and autoantibodies over time and identify traits of non-rituximab treated patients, which would define strong association of disease activity with changes in AAb-levels. METHODS: Seventy-eight patients with seropositive RA were monitored for DAS28, CRP, ESR, anti-cyclic citrullinated peptides (CCP), anti-mutated citrullinated vimentin (MCV), and rheumatoid factor (RF). Using linear mixed regression modelling, factors influencing DAS28 and serum AAb were determined. Patients showing above (good correlators) and below (bad correlators) average correlation of serum AAb with DAS28 were further characterised. RESULTS: In non-rituximab treated patients (88.5%), associations of changes in AAb and DAS28 were strengthened with more morning stiffness (p=0.002), DMARD use (p=0.02), tender joints (p=0.01), swollen joints (p<0.01), higher ESR (p<0.01) and VAS (p<0.001) at baseline. Decrease of anti-CCP was also predicted by longer disease duration (-4.4 U/ml per year disease duration, p=0.048) and/or no erosions (-2.0 U/ml/month, p<0.01) at baseline, whereas erosive disease predicted an increase (+1.4 U/ml/month, p=0.015) in anti-CCP. Conversely, patients with erosive disease showed a trend to decrease RF (-1.9 U/ml/month, p=0.06). CONCLUSIONS: In non-rituximab treated RA patients, the association between disease activity and change in autoantibody levels is not static, but strengthens with increase in signs of inflammation (ESR, VAS, swollen joints, tender joints, morning stiffness) at baseline. Therefore, studies of changes in AAb need to consider baseline inflammation as confounder.

Clinical assessment and ultrasonography in the follow-up of enthesitis in patients with spondyloarthritis: a multicenter ultrasound study in daily clinical practice.

OBJECTIVES: The aim of this study was to compare the clinical Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and an established ultrasound enthesitis score following treatment change in patients with spondyloarthritis and enthesitis with respect to the sensitivity to change and health-related quality of life. MATERIALS AND METHODS: About 145 patients with active ankylosing spondylitis (n=65), psoriatic arthritis without (n=66) or with (n=14) axial involvement undergoing intensification of their treatment were included in this multicenter study. At baseline, after 3 and 6 months, 13 entheses were scored by MASES, ultrasonography was performed for 14 entheses. Assessments of clinical, laboratory and patient-reported outcome measurements were performed. RESULTS: During 6 months of follow-up, MASES was reduced from 5.57 to 3.12 (P<0.001), which was similar to the reduction of the power Doppler sum score from 5.47 to 2.88 (P<0.001). Both MASES and power Doppler ultrasound were responsive at the 3-month follow-up visit, as indicated by a high sensitivity to change in patients initiating anti-tumor necrosis factor treatment (-0.96 for MASES and -0.74 for power Doppler ultrasound). Improvement of enthesitis did not correlate with patient-reported outcomes. CONCLUSION: Clinical assessment by MASES and power Doppler sonography as well reflects anti-tumor necrosis factor treatment response in patients with spondyloarthritis. Improvement of enthesitis did not correlate with changes in quality of life measures.

Rheumatoid Arthritis-Associated Autoimmunity Due to Aggregatibacter actinomycetemcomitans and Its Resolution With Antibiotic Therapy.

Background:Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative coccobacillus recognized as a pathogen in periodontitis and infective endocarditis. By producing a toxin (leukotoxin A, LtxA) that triggers global hypercitrullination in neutrophils, Aa has been recently linked to rheumatoid arthritis (RA) pathogenesis. Although mechanistic and clinical association studies implicate Aa infection in the initiation of autoimmunity in RA, direct evidence in humans is lacking. Case:We describe a 59-year-old man with anti-citrullinated protein antibody (ACPA)-positive RA who presented for evaluation of refractory disease. He was found to have Aa endocarditis. Following antibiotic treatment, joint symptoms resolved and ACPAs normalized. Given the implications for RA immunopathogenesis, we further investigated the bacterial, genetic and immune factors that may have contributed to the patient's clinical and autoimmune phenotypes. Methods:DNA was extracted from serum and used to amplify the Aa leukotoxin (ltx) promoter region by PCR, which was further analyzed by Sanger sequencing. High-resolution identification of HLA alleles was performed by sequenced based typing (SBT). TNF-α, IFN-γ, GM-CSF, IL-1ß, IL-6, IL-8, IL-17A, IL-18, IL-21, and IL-22 were quantified in serum by a multiplex immunoassay. IgG and IgA antibodies to Aa LtxA were assayed by ELISA. Results:Aa genotyping confirmed infection with a highly leukotoxic strain carrying a 530-bp ltx promoter deletion, shown to result in 10- to 20-fold higher bacterial expression of LtxA. Immuno-phenotyping showed high anti-LtxA antibodies, elevated cytokines implicated in RA pathogenesis (Th1/Th17), and specific host susceptibility conferred by three HLA alleles strongly linked to ACPAs and RA (DRB1*04:04, DRB1*15:01, and DPB1*04:01). One year after eradication of Aa, the patient remained free of arthritis and anti-CCP antibodies. Conclusion: In the context of genetic risk for RA, systemic subacute infection with a leukotoxic strain of Aa can drive ACPA production and a clinical phenotype similar to RA.