Transorbital Ultrasound in the Diagnosis of Giant Cell Arteritis.

OBJECTIVES: The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. METHODS: Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. RESULTS: We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: ß=-1.91; p=0.029; EDV: ß=-0.57; p=0.032) and significantly elevated OND (ß = 0.79; p=0.003) compared with controls. RI did not significantly differ from controls (ß=-0.06, p=0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (p=0.048) and EDV (p=0.040). No association was found with RI (p=0.249), while a positive significant association was noted with OND (p<0.001). CONCLUSIONS: This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.

Follow-up ultrasound examination in patients with newly diagnosed giant cell arteritis.

OBJECTIVES: Ultrasound is a standard tool to diagnose giant cell arteritis (GCA). Until now, only few studies investigated the role of ultrasound in the follow-up of GCA. The aim of this study was to assess the changes in the intima media thickness (IMT), total number of affected arteries and provisional OMERACT GCA ultrasonography score (OGUS) in a 12-months follow-up period. METHODS: Patients with newly diagnosed GCA were prospectively enrolled. Ultrasound examinations of facial, temporal, carotid, vertebral and axillary arteries were performed at baseline, after three, six, nine and 12 months. Changes of IMT, total number of affected arteries, and OGUS values were evaluated. In a subgroup of patients, exams were conducted weekly in the first 100 days. RESULTS: Fifty patients were enrolled, 36 completed the follow-up. Significant reductions in IMT, total number of affected arteries and OGUS were observed. Eighteen patients presented to weekly exams. The mean IMT of the axillary artery normalized after seven days, while IMT of the common temporal artery normalized after 50 days. The mean OGUS values were below one after six months. There were no differences in IMT changes between GCA patients with or without PMR or between those with and without additional tocilizumab treatment. A relapse occurred in 4 patients. At relapse, mean IMT and OGUS were higher as compared with the preceding assessment. No predictive values indicating a relapse were identified. CONCLUSION: Vascular ultrasound is sensitive to change in GCA. The presence of PMR or treatment with tocilizumab did not affect IMT decrease.

Comparative analysis of contemporary anti-double stranded DNA antibody assays for systemic lupus erythematosus.

Objective: Elevated double-stranded DNA (dsDNA) antibody levels in blood serum are considered a disease-specific marker in systemic lupus erythematosus (SLE), correlate with disease activity and the incidence of lupus nephritis, and can be detected in up to 86% of all SLE cases. Despite the high clinical relevance, the variety of dsDNA antibody testing methods with heterogenous performance in clinical use remains challenging. This study is the first to prospectively investigate the performance of two of today's most commonly applied anti-dsDNA testing methods head-to-head under real-world conditions, as well as their correlation with other clinical and serological disease parameters in SLE patients. Methods: In this prospective study, all SLE patients undergoing treatment at the Department of Rheumatology at the University Hospital Bonn within a 13-months period (n=41) and control patients without connective-tissue disease (n=51) were consecutively enrolled and examined. For all study participants' serum samples both anti-dsDNA-NcX enzyme-linked immunoassay testing EUROIMMUN, Luebeck, Germany) and the fluorescence immunoassay ELiA dsDNA (Thermo Fisher Scientific, Waltham, USA) were performed. In addition, demographic data, further laboratory values and disease activity parameters were recorded. Clinical disease activity was assessed by SLEDAI-2K. Results: Both assays showed high specificity (anti-dsDNA-NcX ELISA: 0.9, ELiA dsDNA: 0.959), but there were notable differences in sensitivity (anti-dsDNA-NcX ELISA: 0.51, ELiA dsDNA: 0.38). Pearsons's correlation yielded a positive correlation between anti-dsDNA concentrations and CRP concentrations for the anti-dsDNA-NcX ELISA (R=0.22; p=0.038) and a mild-to-moderate inverse correlation between concentrations of anti-dsDNA and complement C4 for the ELiA dsDNA test (R=-0.22; p=0.045) when SLE and control patients were considered together. Other than, no significant correlation between anti-dsDNA concentrations and clinical or laboratory findings was found for either test procedure. Conclusion: Both anti-dsDNA antibody assays represent reliable examination methods with high specificity for the diagnosis of SLE that fulfill EULAR/ACR requirements. However, the anti-dsDNA-NcX ELISA showed superior sensitivity and significant correlation with disease activity (as measured by CRP concentrations).

Prevalence and characteristics of giant cell arteritis in patients with newly diagnosed polymyalgia rheumatica - a prospective cohort study.

Background: It is known that giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) often occur together. So far, the prevalence of GCA in newly diagnosed PMR patients has not been evaluated in a prospective ultrasound study. Objective: The aim of this study was to assess the prevalence of GCA using vascular ultrasound in patients with newly diagnosed PMR. Design: A consecutive cohort of newly diagnosed PMR patients was prospectively evaluated for the presence of GCA with the use of systematic musculoskeletal and vascular ultrasound examination. Methods: Overall, 60 patients with newly diagnosed PMR were prospectively enrolled. Symptoms and laboratory findings were collected. All patients underwent ultrasound of shoulder and hip joints, and vascular ultrasound evaluating the facial, temporal, carotid, vertebral and axillary arteries. Patients were diagnosed with GCA if they had ultrasound imaging findings of GCA. Patients with PMR (PMR-group) and patients with PMR and GCA (PMR-GCA-group) were compared, and a C-reactive protein (CRP) cut-off value was evaluated. Results: GCA was diagnosed in 28 of 60 PMR patients (46%). The PMR-group consisted of 20 (62.5%) females with a mean age of 69 (±9.9) years, while the PMR-GCA-group consisted of 11 (39.3%) females with a mean age of 74 (±8.4) years. In 13 of 28 patients (46%) in the PMR-GCA-group, GCA was subclinical and only diagnosed by ultrasound. The PMR-GCA-group showed higher values of joint effusion and significantly higher CRP values. A CRP cut-off value of 26.5 mg/litre (reference range 0-5 mg/litre) yielded a sensitivity of 66% with a specificity of 73% for GCA. Conclusion: GCA was found in 46% of newly diagnosed PMR patients; 22% of the patients with PMR had asymptomatic GCA. Joint effusions were higher in the PMR-GCA-group, with significant results for the hip joint. A CRP cut-off value of ⩾26.5 mg/litre in PMR can help in the identification of subclinical GCA.

Prospective double-blind study on the value of musculoskeletal ultrasound by dermatologists as a screening instrument for psoriatic arthritis.

OBJECTIVES: This study evaluated musculoskeletal ultrasound (MSUS) use by dermatologists previously trained on a novel handheld, chip-based ultrasound device (HHUD) to screen for early PsA. METHODS: Twelve dermatologists were recruited to screen psoriasis patients for PsA using the novel HHUD in one major hospital in Bonn (Germany) and six private practices in surrounding regions. Patient screening was based on medical history, clinical examination, and the GEPARD questionnaire paired with an MSUS examination of up to three painful joints. All screened patients were then referred to rheumatologists, who determined the final diagnosis. The screening effect of MSUS was assessed according to its sensitivity and specificity before and after its application. RESULTS: Between 1 October 2020 and 26 May 2021, a total of 140 psoriasis patients with arthralgia participated in this study. PsA was diagnosed in 19 (13.6%) cases. Before applying MSUS, dermatologists' screening sensitivity and specificity were recorded as 88.2% and 54.4%, respectively, while after applying MSUS the sensitivity and specificity changed to 70.6% and 90.4%, respectively. MSUS led to a change of PsA suspicion in 46 cases, with PsA no longer being suspected in 45 of them. CONCLUSION: This study was able to demonstrate that PsA screening using MSUS by previously trained dermatologists can lead to more precise PsA detection and potentially decreased rheumatologist referral rates.

Changes in ultrasound imaging of joints, entheses, bursae and tendons 24 and 48 h after adjusted weight training.

Background: Joint effusion and enthesitis are common ultrasound findings in rheumatic diseases such as rheumatoid arthritis or spondyloarthritis. However, changes of joints and entheses were not only observed in patients but also in physically active individuals and athletes. Objectives: The purpose of this study was to evaluate joint, entheseal, bursal and tendon musculoskeletal ultrasound (MSUS) findings in large and medium joints of young healthy individuals after completing a standardised weight training. Design: This is a prospective cohort study. Methods: MSUS examinations of large- and medium-sized joints, and related entheseal sites, bursae and tendons were performed on young healthy individuals (ages 18-30 years). Before, 24 and 48 h after completing 1 h of standardised weight exercise, the subjects were evaluated by MSUS. The development of the MSUS findings and associated effects were examined using generalised linear mixed effects models. Results: In total, 51 healthy individuals (52.9% female) with a mean age of 23.7 (±2.5) years were enrolled. The results showed an increase in the number of individuals with at least one joint effusion from 37 (72.5%) before the weight training to 48 (94.1%) after 48 h. Entheses with pathologies were observed in 14 participants (27.5%) at baseline, increasing to 29 participants (56.9%) 48 h after the weight training. Biceps tendon sheath effusion was detected in 9 individuals (17.6%) prior to training, rising to 22 individuals (43.1%) after 48 h. A significant increase in the number of joints with effusion and abnormal entheses within 48 h after the weight training was indicated by the generalised linear mixed effects models. Conclusion: Within 48 h after the weight training session, a significant increase in the prevalence of joint effusion in large and medium joints and the prevalence of abnormal entheses was observed. As a result, when performing and interpreting an MSUS examination, the patient's physical activities should be taken into account.

The role of dual energy computed tomography in the differentiation of acute gout flares and acute calcium pyrophosphate crystal arthritis.

OBJECTIVES: To analyse the diagnostic impact of dual energy computed tomography (DECT) in acute gout flares and acute calcium pyrophosphate (CPP) crystal arthritis when compared to the gold standard of arthrocentesis with compensated polarised light microscopy. Microscopy results were also compared to musculoskeletal ultrasound (MUS), conventional radiographs, and the suspected clinical diagnosis (SCD). METHODS: Thirty-six patients with a suspected gout flare (n = 24) or acute CPP crystal arthritis (n = 11, n = 1 suffered from neither) who received a DECT and underwent arthrocentesis were included. Two independent readers assessed DECT images for signs of monosodium urate crystals or calcium pyrophosphate deposition. RESULTS: Sensitivity of DECT for gout was 63% (95% CI 0.41-0.81) with a specificity of 92% (0.41-0.81) while sensitivity and specificity for acute CPP arthritis were 55% (0.23-0.83) and 92% (0.74-0.99), respectively. MUS had the highest sensitivity of all imaging modalities with 92% (0.73-0.99) and a specificity of 83% (0.52-0.98) for gout, while sensitivity and specificity for acute CPP crystal arthritis were 91% (0.59-1.00) and 92% (0.74-0.99), respectively. CONCLUSION: DECT is an adequate non-invasive diagnostic tool for acute gout flares but might have a lower sensitivity than described by previous studies. Both MUS and SCD had higher sensitivities than DECT for acute gout flares and acute CPP crystal arthritis.

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.

Development and Proof of Concept of a Low-Cost Ultrasound Training Model for Diagnosis of Giant Cell Arteritis Using 3D Printing.

OBJECTIVES: Currently, ultrasound (US) is widely used for the diagnosis of giant cell arteritis (GCA). Our aim was to develop a low-cost US training model for diagnosis of GCA of the temporal and axillary artery using a modern 3D printing system. METHODS: We designed an US training model, which enables measurement of the intima-media thickness (IMT) of temporal and axillary arteries using Autodesk Fusion360. This model was printed using a modern 3D printer (Formlabs Form3) and embedded in ballistic gelatine. The ultrasound images including measurement of the IMT by ultrasound specialists in GCA were compared to ultrasound images in acute GCA and healthy subjects. RESULTS: Our ultrasound training model of the axillary and temporal artery displayed a very similar ultrasound morphology compared to real US images and fulfilled the OMERACT ultrasound definitions of normal and pathological temporal and axillary arteries in GCA. The IMT measurements were in line with published cut-off values for normal and pathological IMT values in GCA and healthy individuals. When testing the models on blinded US specialists in GCA, they were identified correctly in all test rounds with an intra-class coefficient of 0.99. CONCLUSION: The production of low-cost ultrasound training models of normal and pathological temporal and axillary arteries in GCA, which fulfil the OMERACT ultrasound definitions and adhere to the published IMT cut-off values in GCA, is feasible. Ultrasound specialists identified each respective model correctly in every case.

Do patients with non-radiographic axial spondylarthritis differ from patients with ankylosing spondylitis?

OBJECTIVE: Patients with axial spondylarthritis (SpA) who have structural changes in the sacroiliac joints and/or the spine have been classified as having ankylosing spondylitis (AS), while those without such changes are now classified as having nonradiographic axial SpA (nr-axSpA). The differentiating features are incompletely understood. METHODS: Data from 100 consecutive patients with axial SpA not treated with tumor necrosis factor antagonists were compared clinically and with laboratory parameters, spinal radiographs, and magnetic resonance imaging (MRI) of the spine. Standardized clinical assessment tools were used to assess health status. RESULTS: AS was diagnosed in 56 patients and nr-axSpA in 44 patients. Signs of inflammation were significantly higher in patients with AS than in patients with nr-axSpA, with a median C-reactive protein level of 8.0 versus 3.8 mg/liter, a median Ankylosing Spondylitis Disease Activity Score of 2.2 versus 2.8, respectively, and a median amount of spinal inflammatory lesions on MRI of 2.0 versus 0.0, respectively. Significant differences between these 2 groups were seen in sex (76.8% male AS patients versus 31.8% male nr-axSpA patients). Clinical variables did not differ between patients with AS and nr-axSpA (Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life questionnaire, Short Form 36 health survey). CONCLUSION: Patients with nr-axSpA were characterized by the low proportion of male patients and the low burden of inflammation compared to patients with AS. While both groups did not differ regarding health status, disease activity, and physical function, they did differ in signs of inflammation; all were higher in patients with AS. Since many patients with nr-axSpA had not developed structural changes after years of symptoms, we propose that those patients should not be regarded as having preradiographic AS but rather as having nr-axSpA.