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.

Recommendations for defining giant cell arteritis fast-track clinics. English version.

A German expert committee recommends defining fast-track clinics (FTC) for the acute diagnosis of giant cell arteritis (GCA) as follows: 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 neurology and ophthalmology consultations, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT, possibly CT), and for temporal artery biopsy.

[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.

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.

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.

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.

[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.

[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.

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.

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.

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.

The ability of rheumatologists blinded to prior workup to diagnose rheumatoid arthritis only by clinical assessment: a cross-sectional study.

Objectives: We aimed to study the ability of board-certified rheumatologists, blinded to all prior diagnostic test results, to establish the presence/absence of an inflammatory rheumatic disease (IRD) or RA among polyarthralgia or arthritis patients, solely relying on clinical assessment. Methods: We performed a prospective, examiner-blinded, cross-sectional study documenting the diagnostic work in four sequential steps (medical history, physical examination, musculoskeletal ultrasonography and laboratory tests) of board-certified rheumatologists in a convenience cohort of 100 patients referred for inpatient diagnostic workup to a tertiary care rheumatology centre. Results: The ability to correctly identify patients with or without an IRD (diagnostic accuracy) increased from 27% after the clinical assessment to 53% after the ultrasonography and to 70% after taking laboratory test results into account. The corresponding values for correctly identifying patients with or without RA were 19, 42 and 60%, respectively. Therefore the diagnostic accuracy of solely clinical assessment for determining the diagnosis of IRD or RA compared with the diagnosis established by a consecutive thorough in-patient workup was only 27 and 19% in our cohort, respectively. Pretreatment with corticosteroids (in the prior 7 days) vs none did not alter these results substantially (20 vs 29% for IRD, 15% vs 20% for RA). Conclusion: Experienced rheumatologists, if deprived of information on prior external imaging and laboratory workup by blinding, were not able to correctly classify the majority of patients presenting with polyarthralgia or arthritis symptoms for inpatient workup, relying only on a brief symptom-focused medical history and physical examination.

Impact of esophagogastroduodenoscopy and ileocolonoscopy on diagnosis and therapy in patients with rheumatic diseases-a retrospective cohort study.

OBJECTIVES: Many rheumatic diseases as well as their medications may cause gastrointestinal (GI) pathologies; in addition, some primary GI diseases may contribute or lead to rheumatic disease manifestations. The aim of this study is to analyze the clinical relevance of esophagogastroduodenoscopy (EGD) and ileocolonoscopy (IC) in patients suffering from inflammatory rheumatic diseases. METHODS: A retrospective chart review was performed for all rheumatological inpatients who underwent EGD and/or IC within 2 years. RESULTS: Within 2 years, 456 patients (261 female, 195 male) underwent 752 endoscopic investigations of the GI tract (419 EGDs and 333 ICs). Of all patients, 152 (33.3%) did not report any GI complaints. However, 28 of these asymptomatic patients (18.4%) suffered from esophagitis, a gastric ulcer could be identified in 20 patients (13%), whereas unspecific colitis was diagnosed in 19 patients (12.5%). In addition, 14 patients (9.2%) suffered from clinically unapparent Crohn's disease and two patients from Whipple's disease. In one patient with polymyalgia rheumatica, colon cancer was diagnosed. Altogether 304 patients reported GI complaints. Of these, 292 (39%) endoscopic investigations had impact on the final diagnosis or therapeutic strategy. The antirheumatic medication or the concomitant medication was changed in 18% of the patients due to the endoscopic findings; in 29 patients (6.5%) the initially clinically presumed diagnosis had to be corrected. In 70 patients (15%) with an undefined rheumatic diagnosis prior to endoscopy, endoscopic findings were decisive to establish the final diagnosis. CONCLUSION: EGD and IC have a high diagnostic impact on patients with rheumatic diseases presenting with or without concomitant GI symptoms.

The US7 score is sensitive to change in a large cohort of patients with rheumatoid arthritis over 12 months of therapy.

PURPOSE: To determine the sensitivity to change of the US7 score among RA patients under various therapies and to analyze the effect of each therapeutic option over 1 year. To estimate predictors for development of destructive bone changes. METHODS: Musculoskeletal ultrasound (US7 score), DAS28, CRP and ESR were performed in 432 RA patients at baseline and after 3, 6 and 12 months. The cohort was divided into four sub-groups: first-line DMARDs (Group 1; 27.3%), therapy switch: DMARDs to second DMARDs (Group 2; 25.0%), first-line biologic after DMARDs therapy (Group 3; 35.4%) and therapy change from biologic to second biologic (Group 4; 12.3%). RESULTS: The US7 synovitis and tenosynovitis sum scores in grey-scale (GSUS) and power Doppler ultrasound (PDUS) as well as ESR, CRP decreased significantly (p<0.05) after 12 months in group 1 to 3. Group 1+2 also illustrated a significant change of DAS28 after 1 year (p<0.001). Only in Group 4, the US7 erosion sum score decreased significantly from 4.3 to 3.6 (p=0.008) after 1 year. Predictors capable of forecasting US erosions after one year were: higher score of US7 synovitis (p<0.001), of US7 erosions in GSUS (p<0.001), as well as of DAS28 (p<0.001) at baseline. CONCLUSIONS: The comparable developments of the US7 score with clinical and laboratory data illustrates its potential to reflect therapeutic response. Therefore, the novel US7 score is sensitive to change. Patients who switched from one biologic to another exhibited a significant decline in erosions after 12 months, while the erosions scores in the other groups were stable.

The value of colour Doppler sonography of the knee joint: a useful tool to discriminate inflammatory from non-inflammatory disease?

OBJECTIVE: To determine the diagnostic value of colour Doppler ultrasound (CDUS) in patients with inflammatory arthritis (IA) vs non-inflammatory disease (e.g. OA) of the knee joint. METHODS: Standardized CDUS examinations were performed in 111 knee joints of 106 patients (70 women and 36 men) presenting with severe OA (n = 72) or confirmed IA (n = 39) of one or both knee joints to determine the degree of synovial inflammation in a semiquantitative fashion. To definitely distinguish inflammatory from non-inflammatory disease, SF was obtained from every patient within 24 h after sonography and analysed SFs containing ≤1000 white blood cells (WBC)/µl were considered non-inflammatory, whereas ≥5000 WBC/µl were classified as inflammatory. RESULTS: The CDUS sum score of OA patients was determined to be 3.3 (range 0-8). In contrast, IA patients exhibited significantly elevated synovitis score of 5.3 (range 3-9) (P < 0.001). However, high synovial CDUS activity could be observed in OA patients sporadically. Therefore, there is no definitive CDUS threshold that clearly separates OA from IA patients. CONCLUSION: CDUS is a valuable instrument to assist clinicians in distinguishing OA from IA of the knee joint, but nevertheless should always be interpreted within the clinical context.