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Most individuals with rare diseases initially consult their primary care physician. For a subset of rare diseases, efficient diagnostic pathways are available. However, ultra-rare diseases often require both expert clinical knowledge and comprehensive genetic diagnostics, which poses structural challenges for public healthcare systems. To address these challenges within Germany, a novel structured diagnostic concept, based on multidisciplinary expertise at established university hospital centers for rare diseases (CRDs), was evaluated in the three year prospective study TRANSLATE NAMSE. A key goal of TRANSLATE NAMSE was to assess the clinical value of exome sequencing (ES) in the ultra-rare disease population. The aims of the present study were to perform a systematic investigation of the phenotypic and molecular genetic data of TRANSLATE NAMSE patients who had undergone ES in order to determine the yield of both ultra-rare diagnoses and novel gene-disease associations; and determine whether the complementary use of machine learning and artificial intelligence (AI) tools improved diagnostic effectiveness and efficiency.ES was performed for 1,577 patients (268 adult and 1,309 pediatric). Molecular genetic diagnoses were established in 499 patients (74 adult and 425 pediatric). A total of 370 distinct molecular genetic causes were established. The majority of these concerned known disorders, most of which were ultra-rare. During the diagnostic process, 34 novel and 23 candidate genotype-phenotype associations were delineated, mainly in individuals with neurodevelopmental disorders.To determine the likelihood that ES will lead to a molecular diagnosis in a given patient, based on the respective clinical features only, we developed a statistical framework called YieldPred. The genetic data of a subcohort of 224 individuals that also gave consent to the computer-assisted analysis of their facial images were processed with the AI tool Prioritization of Exome Data by Image Analysis (PEDIA) and showed superior performance in variant prioritization.The present analyses demonstrated that the novel structured diagnostic concept facilitated the identification of ultra-rare genetic disorders and novel gene-disease associations on a national level and that the machine learning and AI tools improved diagnostic effectiveness and efficiency for ultra-rare genetic disorders.

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.

Abstract 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. Key Points• DECT offers a lower sensitivity for acute gout flares than previously described.• DECT sensitivity for acute CPP crystal arthritis is less than the already validated ultrasound.

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.

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.

OBJECTIVE To determine the prevalence of echocardiographic findings and their change over time in patients with connective tissue diseases (CTDs) and to analyse which findings were associated with escalation of immunosuppressive therapy. METHOD We conducted a retrospective cohort study of consecutive hospitalized patients from a tertiary rheumatology referral centre who received transthoracic echocardiography between 1 January 2006 and 31 December 2015. We tested for associations between echocardiographic findings and treatment escalation via Fisher's exact test; p

Medical education has been transformed during the COVID-19 pandemic, creating challenges regarding adequate training in ultrasound (US). Due to the discontinuation of traditional classroom teaching, the need to expand digital learning opportunities is undeniable. The aim of our study is to develop a tele-guided US course for undergraduate medical students and test the feasibility and efficacy of this digital US teaching method. A tele-guided US course was established for medical students. Students underwent seven US organ modules. Each module took place in a flipped classroom concept via the Amboss platform, providing supplementary e-learning material that was optional and included information on each of the US modules. An objective structured assessment of US skills (OSAUS) was implemented as the final exam. US images of the course and exam were rated by the Brightness Mode Quality Ultrasound Imaging Examination Technique (B-QUIET). Achieved points in image rating were compared to the OSAUS exam. A total of 15 medical students were enrolled. Students achieved an average score of 154.5 (SD ± 11.72) out of 175 points (88.29 %) in OSAUS, which corresponded to the image rating using B-QUIET. Interrater analysis of US images showed a favorable agreement with an ICC (2.1) of 0.895 (95 % confidence interval 0.858 ICC 0.924). US training via teleguidance should be considered in medical education. Our pilot study demonstrates the feasibility of a concept that can be used in the future to improve US training of medical students even during a pandemic.ZIEL: Das Ziel dieser Studie war die Konzeption eines telemedizinischen Ultraschall (US)-Kurses für Medizinstudierende zu Zeiten der COVID-19-Pandemie mit anschließender Evaluation praktischer Untersuchungskompetenzen. Es wurde ein telemedizinischer Ultraschallkurs mit Medizinstudierenden durchgeführt. Die Studierenden absolvierten insgesamt 7 US-Module. Jedes Modul wurde in einem Flipped-Classroom-Konzept mit der Amboss-Plattform konzipiert, um den Studierenden die Möglichkeit zu geben, zusätzliches E-Learning-Material zu nutzen, das optional war und Informationen zu jedem der US-Module lieferte. Als Abschlussprüfung wurde eine objektive Bewertung der US-Kompetenzen (OSAUS) durchgeführt. Zusätzlich wurden die US-Bilder aus Kursstunden und Prüfung mit der B-QUIET-Rating-Methode bewertet und die dort erreichten Punkte mit den Ergebnissen der OSAUS-Prüfung verglichen. Insgesamt nahmen 15 Medizinstudierende teil. In OSAUS wurden durchschnittlich 154,5 (SD ± 11,72) von insgesamt 175 Punkten erreicht (88,29 %). Die OSAUS-Ergebnisse stimmen mit der Punktzahl aus der Bildbewertung mit B-QUIET überein. Die Interrater-Analyse der bewerteten US-Bilder zeigte eine gute Übereinstimmung mit einem ICC (2,1) von 0,895 (95 %-Konfidenzintervall 0,858–0,924). Die US-Lehre mittels Teleguidance hat sich in dieser Pilotstudie als erfolgreiches Lehrkonzept erwiesen. Dieses zukunftsweisende Lehrkonzept ermöglicht zudem die US-Ausbildung von Medizinstudierenden in Zeiten der COVID-19-Pandemie, in denen Präsenzlehre nicht möglich ist.

Zusammenfassung Hintergrund Die Hypophosphatasie (HPP) ist eine genetische Erkrankung, die durch eine oder mehrere Mutationen im Gen für alkalische Phosphatase (ALP) verursacht wird, verantwortlich für die Kodierung der gewebespezifischen ALP und für den Mineralisierungsprozess. Ziel der Arbeit Bestimmung der Prävalenz der HPP bei rheumatologischen Patienten. Material und Methoden Retrospektive Analyse der Krankenakten aller erwachsener Patienten mit pathologisch erniedrigten gesamt ALP-Werten ( Ergebnisse Bei 60 von 2289 Patienten (2,62 %) zeigten sich pathologisch niedrige ALP-Werte, bei 30 von ihnen (1,31 %) wurden persistierend niedrige ALP-Werte festgestellt. Bei 19 dieser 30 Patienten wurde ein Gentest für ALP-Genmutationen durchgeführt. Sieben der 19 Patienten (36,84 %) hatten HPP-Zeichen (Insuffizienzfrakturen oder schlechter Zahnstatus seit der Kindheit), alle mit pathologischer ALP-Mutation. Drei dieser Patienten (15,78 %) hatten jeweils eine Insuffizienzfraktur mit normwertiger Knochendichtemessung in der Vorgeschichte. Insgesamt 13 von 19 Patienten wiesen (68,42 %) Mutationen im ALP-Gen auf. Interessanterweise wurde keine Assoziation mit einer Chondrokalzinose festgestellt. Diskussion Die HPP scheint eine unterdiagnostizierte Erkrankung mit einem höheren Anteil betroffener Patienten, welche in der Rheumatologie vorstellig werden, zu sein. Daher sollten zukünftige Studien darauf abzielen, ein Diagnostikprotokoll in der klinischen Praxis zu entwickeln.

ZusammenfassungDie eosinophile Fasziitis (EF, auch Shulman-Syndrom) ist eine seltene Erkrankung des Bindegewebes mit entzündlicher Verdickung der Faszien sowie Schwellung und Verhärtung der Haut. Betroffen sind v. a. die distalen Extremitäten. Typische klinische Befunde stellen eine lokalisierte Schwellung und Verhärtung der Haut sowie das Groove-Sign (deutsch: Rillenzeichen/negatives Venenzeichen/Matratzenphänomen) dar. Der Goldstandard für die Diagnosesicherung ist bisher der bioptische Nachweis entzündlich verdickter Faszien. In der Literatur wird alternativ die Diagnosesicherung durch MRT-Bildgebung diskutiert. Wir berichten über einen Fall von asymmetrischer EF bei einem 54 Jahre alten, männlichen Deutschen. Die Vorstellung erfolgte mit schmerzhafter Verhärtung im Bereich des rechten Unterarms sowie charakteristischem Groove-Sign und einer Bewegungseinschränkung der rechten Hand. Im Blutbild zeigte sich eine Eosinophilie mit 0,57 G/l bzw. 9,6 % (norm. 0,05–0,5 G/l und 0,5–5,5 %), ANAs und ENAs waren negativ. Die Diagnosesicherung erfolgte histologisch, zusätzlich konnten wir verdickte Faszien sowohl im MRT als auch in der Sonographie nachweisen. Im Verlauf manifestierte sich die EF auch am linken Malleolus lateralis. Die Therapie erfolgte mit Prednisolon und Methotrexat.

Eosinophilic fasciitis (EF, also known as Shulman syndrome) is an uncommon connective tissue disease characterized by inflammatory thickening of the fasciae as well as swelling and hardening of the skin. It mostly affects the lower extremities. Swollen and indurated skin, together with the groove sign, are typical clinical signs. So far, biopsy evidence of inflammation and thickening of the fascia has been the gold standard for diagnosis. Magnetic resonance imaging (MRI) is mentioned in the literature as an alternative method for confirming the diagnosis. We present a case of asymmetric EF in a 54-year-old German male. He came with painful induration of the right forearm, with a characteristic groove sign and limitation of motion of the right hand. The blood count revealed eosinophilia with 0.57 G/l or 9.6% (normal: 0.05-0.5 G/l and 0.5-5.5%), ANA and ENA were negative. The diagnosis was confirmed histologically and we were able to detect a thickened fascia in MRI and ultrasound imaging. The EF also appeared in the left lateral malleolus during the course of the illness. Treatment was carried out with prednisolone and methotrexate.Die eosinophile Fasziitis (EF, auch Shulman-Syndrom) ist eine seltene Erkrankung des Bindegewebes mit entzündlicher Verdickung der Faszien sowie Schwellung und Verhärtung der Haut. Betroffen sind v. a. die distalen Extremitäten. Typische klinische Befunde stellen eine lokalisierte Schwellung und Verhärtung der Haut sowie das Groove-Sign (deutsch: Rillenzeichen/negatives Venenzeichen/Matratzenphänomen) dar. Der Goldstandard für die Diagnosesicherung ist bisher der bioptische Nachweis entzündlich verdickter Faszien. In der Literatur wird alternativ die Diagnosesicherung durch MRT-Bildgebung diskutiert. Wir berichten über einen Fall von asymmetrischer EF bei einem 54 Jahre alten, männlichen Deutschen. Die Vorstellung erfolgte mit schmerzhafter Verhärtung im Bereich des rechten Unterarms sowie charakteristischem Groove-Sign und einer Bewegungseinschränkung der rechten Hand. Im Blutbild zeigte sich eine Eosinophilie mit 0,57 G/l bzw. 9,6 % (norm. 0,05–0,5 G/l und 0,5–5,5 %), ANAs und ENAs waren negativ. Die Diagnosesicherung erfolgte histologisch, zusätzlich konnten wir verdickte Faszien sowohl im MRT als auch in der Sonographie nachweisen. Im Verlauf manifestierte sich die EF auch am linken Malleolus lateralis. Die Therapie erfolgte mit Prednisolon und Methotrexat.

Die Hamochromatose ist eine Eisenspeicherkrankheit. Man unterscheidet zwischen der haufigen, mit einer Haufigkeit von ca. 1/200–1/400 vorkommenden hereditaren Hamochromatose (HH), und der selteneren sekundaren Hamochromatose als Folge anderer Erkrankungen. Dieser Review fokussiert sich auf die HH. Bei der HH finden sich Mutationen im HFE-Gen oder seltener im Transferrinrezeptor-2-Gen. Hierbei kommt es im Dunndarm zu einer vermehrten Eisenaufnahme, welches sich daraufhin in verschiedenen Organen ablagert. Unbehandelt konnen sich so beispielsweise Lebererkrankungen, Erkrankungen der endokrinen Drusen, Hauterscheinungen, Arthritis oder Herzinsuffizienz entwickeln. Ungefahr die Halfte der HH-Patienten entwickelt eine Arthritis. Eine fruhe Diagnosestellung ist wichtig, um die Entstehung von Krankheiten zu verhindern. Bereits einfache Laboruntersuchungen und nativradiologische Bildgebung konnen erste wichtige diagnostische Hinweise liefern. Die Behandlung sollte die Prophylaxe und Behandlung der Folgekrankheiten beinhalten. Wichtigste Masnahme sind regelmasige Aderlasse. Chelatbildner konnen additiv eingesetzt werden. Hemochromatosis is an iron overload disease. It exists as hereditary, primary (HH) form with an incidence of 1/200–1/400 and a secondary form. This article reviews primary hemochromatosis. In this disease, mutations of the HFE gene or rarely of the transferrinreceptor 2-gene, cause an increase of resorption of iron by the bowel. Following arthritis, cardiac diseases, like heart failure, liver diseases, endocrinological diseases or skin lesions are possible concomitant diseases. About 50 % of all patients develop arthritis. Early diagnosis is therefore important, in order to prevent development of the above-mentioned diseases. Initially basic laboratory parameters and conventional radiography can help in diagnosis of suspicious patients. Treatment should consist of prevention and treatment of concomitant diseases. The most important therapy is phlebotomy. Additionally, therapy with chelating agents can be indicated.

The aim of this observational study was to compare clinical outcomes including glucocorticoid treatment and relapses between giant cell arteritis (GCA) patients with (axGCA) and without axillary artery involvement (non-axGCA).Axillary artery ultrasound was performed in 101 GCA patients at multiple time points. Patients with signs of vasculitis of the axillary arteries at baseline were compared to patients without signs of axillary artery involvement. Cumulative GC doses and relapse rates were calculated as well as survival curves to compare the time until GC discontinuation and occurrence of the first clinical relapse. A linear mixed model was used to assess the effect of a clinical relapse on the intima media thickness (IMT) in axGCA patients.Sixty-seven patients were classified as axGCA, 34 as non-axGCA patients. Compared with non-axGCA, axGCA patients yielded a higher (albeit not significant) median time until GC discontinuation (42 months (95% CI: 33-84) vs 30 months (95% CI: 21-42), p=0.060) and median cumulative GC dose (6801mg (range 1748-34169) vs 5633mg (range: 2553-19967), p=0.051). Time until the first relapse (axGCA: 12 months (95% CI: 8-42) vs non-axGCA: 13.5 months (95% CI: 6-27), p=0522) and relapse rates (2 (range: 0-16) vs 1 (range: 0-13), p=0.67) were similar in both groups. Relapses resulted in an increase of the IMT by 0.18mm (95% CI: 0.07-0.30, p=0.003).Patients with axGCA have a trend towards longer treatment duration and higher GC requirements as compared to non-axGCA patients. A relapse leads to an increase of the IMT by 0.18mm.

In some patients with antinuclear antibodies (ANA), a pattern called anti-dense-fine-speckled-70 antibody (anti-DFS70) can be detected. Presence of anti-DFS70 is less frequently observed in patients with connective tissue diseases (CTD) and is therefore used as an exclusion criterion by some rheumatologists. To date, however, it is unclear as to what extent the presence of an anti-DFS70 can reliably rule out CTDs.Data of 460 patients who were tested for the presence of anti-DFS70 at University Hospital Bonn, Germany, were analyzed. Patients were examined with regard to clinical symptoms and signs, type of disease, type of CTD, fulfillment of the classification criteria, presence of anti-DFS70, other systemic autoantibodies and ANA titers by indirect immunofluorescence (IIF) assays and line immunoassays. Differences in DFS70 antibody status between patients with CTD were examined. In addition, specificity, sensitivity, and positive predictive values for different ANA titers were calculated.In 182 of the 460 patients (of whom 79.8% were female), CTD was diagnosed. 354 patients (77.0%) tested negative, 81 (17.6%) positive and 25 (5.4%) borderline for anti-DFS70. Twenty-one patients (25.9%) with a positive result had CTD. No significant differences were observed between anti-DFS70 positive and anti-DFS70 negative patients with CTD concerning age, gender, symptoms, clinical signs, and other disease-specific antibodies. However, of these 21 patients, only one patient showed the monospecific appearance of anti-DFS70. Anti-DFS70 had a sensitivity and a specificity of 26.9% and 86.8%, respectively, with a positive predictive value of 68.2% at an ANA titer of ≥1:160 with respect to the absence of CTD.Autoantibodies to DFS70 seem to be prevalent in CTD patients and are thus not a good exclusion criterion. The monospecific occurrence of anti-DFS70 can, however, be helpful in ambiguous situations.

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.

Background/objectivesTo maintain and optimise the quality of care provided by health professionals in rheumatology (HPRs), adequate educational offerings are needed. This task force (TF) aimed to develop evidence-based recommendations for the generic core competences of HPRs, with specific reference to nurses, physical therapists (PTs) and occupational therapists (OTs) to serve as a basis for their postgraduate education.MethodsThe EULAR standardised operating procedures for the development of recommendations were followed. A TF including rheumatologists, nurses, PTs, OTs, patient-representatives, an educationalist, methodologists and researchers from 12 countries met twice. In the first TF meeting, 13 research questions were defined to support a systematic literature review (SLR). In the second meeting, the SLR evidence was discussed and recommendations formulated. Subsequently, level of evidence and strength of recommendation were assigned and level of agreement (LoA) determined (0–10 rating scale).ResultsThree overarching principles were identified and 10 recommendations were developed for the generic core competences of HPRs. The SLR included 79 full-text papers, 20 of which addressed the competences, knowledge, skills, attitudes and/or educational needs of HPRs from multiple professions. The average LoA for each recommendation ranged from 9.42 to 9.79. Consensus was reached both on a research and educational agenda.ConclusionEvidence and expert opinion informed a set of recommendations providing guidance on the generic core competences of HPRs. Implementation of these recommendations in the postgraduate education of HPRs at the international and national level is advised, considering variation in healthcare systems and professional roles.

Background:Management of psoriatic arthritis (PsA) and other rheumatological diseases requires an interdisciplinary approach involving dermatologists and rheumatologists. The aim of the study was to analyze the specialized dermatological-rheumatological management before and after foundation of a PsA center. Methods:A retrospective cohort study of all dermatology-rheumatology consultations during two periods was conducted. Period one, from April 1st, 2016 to February 28th, 2018 versus period two, from March 1st, 2018 to January 31st, 2020, after foundation of a PsA center. Clinical data on patient characteristics including psoriasis subtypes, clinical symptoms and signs, disease activity scores, classification criteria and comorbidities as well as patient journey were extracted and analyzed.Results: 404 consultations were studied. Close collaboration in a PsA center lead to a relevantly shortened patient journey concerning rheumatological complaints: period 1: median (IQR): 36.0 (10.0-126.0) months, period 2: median (IQR): 24.0 (6.0-60.0) months. Established scores and classification criteria such as GEPARD or CASPAR did not assist in diagnosis of PsA. Arthralgia (p=0.0407), swollen joints (p=0.0151), morning stiffness (p=0.0451) and dactylitis (p=0.0086) helped to distinguish between osteoarthritis and PsA.Conclusions: Clinical signs and symptoms, scores and classification criteria usually assessed were less helpful than expected in diagnosis of PsA and other rheumatological diseases. Close collaboration in a specialized PsA center yielded the fastest way of diagnosis.

Clinical differentiation between gout, osteoarthritis (OA), and calcium pyrophosphate deposition disease (CPPD) remains a hurdle in daily practice without imaging or arthrocentesis. We performed a retrospective analysis of consecutive patients with gout, CPPD, and OA at a tertiary rheumatology center. A total of 277 patients were enrolled, with 164 suffering from gout, 76 from CPPD, and 37 from OA. We used ANOVA and conditional inference tree analysis (Ctrees) to find associations between clinical, laboratory, and imaging data and gout, OA, and CPPD. The sonographic double contour sign was unable to differentiate gout from CPPD. Ctrees were able to exclude OA and CPPD as possible differentials based on elevated uric acid, C-reactive protein (CRP), presence of arterial hypertension, and sex, diagnosing gout with a sensitivity and specificity of 95.1% and 41.6%, respectively. Elevated CRP was observed using simple linear regressions in patients with type II diabetes, higher cumulative joint scores, increased number of affected joints, as well as elevated uric acid, erythrocyte sedimentation rate, and leukocyte count. Ctrees were able to differentiate gout, OA, and CPPD based on just four characteristics. Inflammatory response correlated with type II diabetes, more or larger joint involvement, and elevated uric acid levels.

Background: Immune checkpoint inhibitors (ICIs) improved cancer therapy by inducing a higher immune system activity. This effect can cause rheumatic immune-related adverse events (rh-irAEs), which have not yet been extensively studied. Methods: We analysed 437 patients between 2014 and 2019, treated with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1) at the Clinic for Internal Medicine III, Oncology, Haematology and Rheumatology at the University Hospital Bonn, Germany. Results: Of the 437 patients 60% were males. Patients were mainly treated for melanoma, lung cancer, head and neck tumour and urothelial carcinoma. At least one immune-related adverse event (irAE) was observed in 163 patients (37.3%), including rh-irAE. Most common side effects were rash, colitis and hepatitis. We identified 19 patients (4.3%) with a minimum of one rh-irAE due to ICI therapy; three of those had a pre-existing rheumatic disease. Arthralgia developed most frequently in eight patients (42.1%). Other rh-irAEs were: arthritis ( n = 7; distinguished in rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis and undifferentiated arthritis), myalgia ( n = 2) and myositis ( n = 3). Most rh-irAEs were classified as moderately severe (Common Terminology Criteria of Adverse Events grade 2: 68.4%). Median time between starting ICI therapy and the occurrence of rh-irAE was 109 days (interquartile range 40–420 days). Fifteen patients (78.9%) were treated with glucocorticosteroids. In four cases additional therapy with methotrexate or tocilizumab was required. Even though patients benefited from ICI treatment, therapy had to be discontinued in six of the participants due to rh-irAE. Interestingly, patients with rh-irAE had a significantly higher tumour response compared with patients without rh-irAE (94.4% versus 43.5%; p Conclusion: Rh-irAEs occur under ICI therapy, especially in patients with higher tumour response. However, they are not the most frequent irAE after ICI exposure: 9.3% of all irAEs were rheumatic (20 rh-irAE cases in 19 patients of a total of 215 irAE cases in 163 patients).

Background Giant cell arteritis (GCA) is the most common form of systemic vasculitis in persons aged 50 years and older. Medium and large vessels, like the temporal and axillary arteries, are commonly affected. Typical symptoms are headache, scalp tenderness, jaw claudication and ophthalmological symptoms as loss of visual field, diplopia or amaurosis due to optic nerve ischemia. Tongue pain due to vasculitic affection of the deep lingual artery can occur and has so far not been visualized and followed up by modern ultrasound. Case presentation We report the case of a 78-year-old woman with typical symptoms of GCA, such as scalp tenderness, jaw claudication and loss of visual field, as well as severe tongue pain. Broad vasculitic affection of the extracranial arteries, vasculitis of the central retinal artery and the deep lingual artery could be visualized by ultrasound. Further did we observe a relevant decrease of intima-media thickness (IMT) values of all arteries assessed by ultrasound during follow-up. Especially the left common superficial temporal artery showed a relevant decrease of IMT from 0.49 mm at time of diagnosis to 0.23 mm on 6-months follow-up. This is the first GCA case described in literature, in which vasculitis of the central retinal artery and the lingual artery could be visualized at diagnosis and during follow-up using high-resolution ultrasound. Conclusion High-resolution ultrasound can be a useful diagnostic imaging modality in diagnosis and follow-up of GCA, even in small arteries like the lingual artery or central retinal artery. Ultrasound of the central retinal artery could be an important imaging tool in identifying suspected vasculitic affection of the central retinal artery.

Purpose of Review To discuss and summarize the latest evidence on imaging techniques in giant cell arteritis (GCA) and Takayasu arteritis (TAK). This is a report on the performance of ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (18-FDG-PET), and other emerging imaging techniques in diagnosis, outcome prediction, and monitoring of disease activity. Recent Findings Imaging techniques have gained an important role for diagnosis of large vessel vasculitides (LVV). As signs of vasculitis, US, MRI, and CT show a homogeneous arterial wall thickening, which is mostly concentric. PET displays increased FDG uptake in inflamed artery walls. US is recommended as the initial imaging modality in GCA. MRI and PET/CT may also detect vasculitis of temporal arteries. For TAK, MRI is recommended as the first imaging modality as it provides a good overview without radiation. Extracranial LVV can be confirmed by all four modalities. In addition, MRI and PET/CT provide consistent examination of the aorta and its branches. New techniques such as contrast-enhanced ultrasound, PET/MRI, and auxiliary methods such as “computer-assisted quantitative analysis” have emerged and need to be further validated. Summary Imaging has partly replaced histology for confirming LVV. Provided experience and adequate training, US, MRI, CT, or PET provide excellent diagnostic accuracy. Imaging results need to complement history and clinical examination. Ongoing studies are evaluating the role of imaging for monitoring and outcome measurement.

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 (&ge, 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 &le, 0.001), the presence of joint effusion (p-value &le, 0.001), and the diagnosis of RA (p-value &le, 0.001) were observed. Interrater analysis of ultrasound imaging showed good agreement with Cohen&rsquo, 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 &le, 0.001).

Interstitial lung disease (ILD) is the most common form of pulmonary impairment in patients with rheumatoid arthritis (RA). However, patients with RA or other arthritic diseases such as psoriatic arthritis (PsA) or peripheral spondyloarthritis (pSpA) are at a higher risk of developing several other pulmonary diseases, such as chronic obstructive lung disease (COPD), compared to patients without arthritis. This review aims at summarizing the current knowledge on the prevalence of pulmonary diseases in the above-mentioned forms of arthritis, the challenges faced by prevalence studies in detecting pulmonary diseases in patients with arthritis, as well as possible treatment options. Dyspnea, cough or other pulmonary symptoms in arthritis patients should prompt gradual diagnostic procedures considering pulmonary manifestations as a major cluster of differential diagnosis. However, treatment options often lack solid evidence-based guidelines and referrals to specialized centers are often necessary.

Background: Despite ultrasound being an inherent part of medical education, only a few German medical schools have established a comprehensive ultrasound curriculum. This study aimed to explore medical students' perspectives on ultrasound in medical education (USMed).Results: Between January 1st, 2019 und June 30th, 2019, an online survey was conducted among German medical students via the students' associations and their respective teaching facilities. The survey consisted of 17 items regarding USMed. Statements were rated on a 4-point Likert scale for agreement. In total, 1040 students from 31 German medical faculties participated. The majority (1021, 98.2%) reported a very high to high interest in curricular USMed. Students agreed (n = 945, 90.9%) that USMed would be helpful along their entire course of medical studies. Considering the best starting time for USMed, the opinions of German medical students diverged: students studying in a model curriculum preferred to start in the second year (40.7%) while 49% of the students studying in a traditional curriculum preferred to start in the third year (p ≤ 0.001). An insufficient allotment of time for USMed in the planned curriculum (675, 65%) and a lack of courses run by medical faculty (305, 29.4%) were listed as perceived significant barriers to the participation in USMed. Peer teaching was regarded as an effective method in realizing USMed by 731 (70.3%) students.Conclusion: German medical students are very interested and willing to participate in USMed. There appears to be a high demand for US courses offered by medical schools.

Objective.To test the reliability of Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus-based ultrasound definitions for normal and vasculitic temporal and axillary arteries in patients with giant cell arteritis (GCA) and in controls.Methods.A preliminary 1-day meeting and a full 3-day meeting fulfilling OMERACT Ultrasound Group guidelines were held. Temporal and axillary arteries were examined at 2 timepoints by 12 sonographers on 4 patients with GCA and 2 controls. The aim was to test inter- and intrareader reliability for normal findings, halo sign, and compression sign. In both meetings, patients had established GCA. Pathology was more recent in the full meeting, which was preceded by 6 h of training. Scanning time was 15–20 min instead of 10–13 min.Results.In the preliminary exercise, interreader reliabilities were fair to moderate for the overall diagnosis of GCA (Light κ 0.29–0.51), and poor to fair for identifying vasculitis in the respective anatomical segments (Light κ 0.02–0.46). Intrareader reliabilities were moderate (Cohen κ 0.32–0.64). In the main exercise, interreader reliability was good to excellent (Light κ 0.76–0.86) for the overall diagnosis of GCA, and moderate to good (Light κ 0.46–0.71) for identifying vasculitis in the respective anatomical segments. Intrareader reliability was excellent for diagnosis of GCA (Cohen κ 0.91) and good (Cohen κ 0.71–0.80) for the anatomical segments.Conclusion.OMERACT-derived definitions of halo and compression signs of temporal and axillary arteries are reliable in recent-onset GCA if experienced sonographers (> 300 examinations) have 15–20 min for a standardized examination with prior training and apply > 15 MHz probes.

To examine disease activity parameters in patients with systemic lupus erythematosus (SLE) experiencing flare, infection, both, or neither condition, focusing on erythrocyte sedimentation rate (ESR). This study is a retrospective analysis of 371 consecutive inpatient SLE cases from 2006 to 2015. Cases were classified as flare (n = 147), infection (n = 48), both (n = 23), or neither (n = 135). ESR levels were correlated to C-reactive protein (CRP), ferritin, anti-dsDNA antibodies, complement C3 reduction, serositis, and erythrocyturia with proteinuria (Pearson's correlation). ESR levels were related to an age- and gender-adapted cut-off value (ESRp). We analyzed mean values of age, ESR, ESRp, CRP, ferritin and distribution of anti-dsDNA antibodies, C3 reduction, serositis, and erythrocyturia with proteinuria. Sensitivity and specificity were calculated via receiver operating characteristic or two-by-two table. Association of parameters with disease activity and infection was tested via two-sided chi square test. ESR correlated moderately with CRP in cases with flare and/or infection (r = 0.505-0.586). While ESR and CRP were normal in remission, mean values overlapped in cases with flare, infection, or both. ESRp was higher in flare than in infection (p = 0.048). ESR lost association to activity in infected cases, CRP to infection in flaring cases. ESRp, serositis, and anti-dsDNA antibodies were related to disease activity regardless of infections. Anti-dsDNA antibodies were most sensitive for detecting flares (74%), while serositis, proteinuria with erythrocyturia, anti-dsDNA antibodies, C3 reduction, and ESRp values ≥ 2 were most specific. ESR levels were raised by flares, infections, and age; adapting them to age and gender increased their diagnostic value. Obtaining several parameters remains necessary to differentiate flare from infection.

Background:In the early detection of arthritis, such as psoriatic arthritis (PsA), ultrasound (US) 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. Furthermore, several publications undermine the importance of early PsA detection in psoriasis patients and the key role of the dermatologists in this process.Objectives:The objective of this study was to examine a pilot musculoskeletal ultrasound (MSUS) course designed specifically for dermatologists.Methods:To assess the degree of US expertise of the participants, a questionnaire was conducted before the course. The course concept, based on The German Society for Ultrasound in Medicine (Deutsche Gesellschaft fur Ultraschall in der Medizin, DEGUM) covering only the most important US 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 6 months. Figure 1 shows the modular course concept. A portable US device in combination with a tablet was provided to enable practice between the courses. The final teaching evaluation was carried out as an objective structured clinical examination (OSCE) consisting of three stations, each representing the three course modules. According to the following grade scoring system, the performance rating was checked: < 60 % failed, ≥ 60 - < 70 % sufficient, ≥ 70% - < 80 % satisfying, ≥ 80% - < 90 % good, ≥ 90 % very good.Results:Twelve dermatologists participated. The mean age of our cohort was 39 years (SD ± 9.99 years) with nine females (75 %). Eight were specialists in dermatology in mean for 11.4 years (SD ± 11 years). Four were assistant physicians practicing dermatology in mean for 3.06 years (SD ± 0.97 years).The survey revealed no prior knowledge of MSUS. The overall mean score of all participants in the OSCE was 21.86 (SD ± 2.12) (87.44%) out of a total of 25 points resulting in a good grade. There was no statistically significant difference between the assistant physicians and the specialists in dermatology regarding the OSCE results. Table 1 shows the OSCE results.Table 1.Objective structured clinical examination (OSCE) mean results for all three stationsOSCEstationsMean absoluteMean absoluteStandard DeviationMean percentageStandard DeviationConfidence IntervalGrade118.9218.92+/- 3.0775.67%+/-12.27%67.87-83.46%Sufficient223.8323.83+/-0.9995.33%+/-3.94%92.83-97.84%Very good322.8322.83+/-0.3791.33%+/-1.49%90.39-92.28%Very goodOSCE station 1-321.8621.86+/-2.1287.44%+/-8.49%66.36-108.53%GoodConclusion:The innovative US teaching concept was able to demonstrate, that it is appropriate for the training of dermatologists in MSUS, independently of their age, experience in dermatology and US.Disclosure of Interests:Jakub Grobelski: None declared, Florian Recker: None declared, Dagmar Wilsmann-Theis: None declared, Wolfgang Hartung: None declared, Pantelis Karakostas: None declared, Peter Brossart: None declared, Valentin Schäfer Speakers bureau: AbbVie, Novartis, BMS, Chugai, Celgene, Medac, Sanofi, Lilly, Hexal, Pfizer, Janssen, Roche, Schire, Onkowissen, Royal College London, Consultant of: Novartis, Chugai, AbbVie, Celgene, Sanofi, Lilly, Hexal, Pfizer, Amgen, BMS, Roche, Gilead, Medac, Grant/research support from: Novartis, Hexal, Lilly, Roche, Celgene, Universität Bonn

Background The European League Against Rheumatism (EULAR) recently recommended the use of ultrasound for the detection of inflamed artery walls in giant cell arteritis (GCA) for diagnostic purposes. Intima media thickness (IMT) values, defining the “halo” sign in acute GCA patients, have also recently been proposed. In patients with chronic GCA, already receiving a treatment, the ultrasound appearance of inflamed artery walls changes and becomes difficult to detect.(1-4) IMT measurement may help to identify patients with chronic large-vessel GCA (LV-GCA) by assessing the axillary arteries; however, a cut-off for distinguishing between chronically affected arteries and unaffected ones is not yet available. Objectives To determine an ultrasound IMT cut-off value for axillary arteries in patients with chronic LV-GCA. Methods Ultrasound of temporal and axillary arteries was performed in 127 GCA patients at the time of diagnosis and at one or two follow-up visits. Axillary arteries of GCA patients with sonographic signs of inflammation at the time of diagnosis were compared to unaffected axillary arteries of GCA patients and to axillary arteries of healthy controls. Receiver operating curves (ROC) were calculated using follow-up data to identify the optimal IMT cut-off. Results 148 axillary arteries of GCA patients showed signs of ultrasound inflammation at baseline (=LV-GCA group). The control group consisted of 162 axillary arteries, including 82 (50.6%) axillary arteries of GCA patients without signs of ultrasound inflammation at baseline or follow-up exam and 80 (49.4%) axillary arteries of 40 healthy controls. The mean age and gender distribution of the two groups at follow-up were 71 years (S.D. 7.9) with 69.9% females, respectively in the chronic LV-GCA group and 74 years (S.D. 6.9) with 59.8% females, respectively in the control group. The mean IMT values in the LV-GCA group were 1.14 (S.D. 0.38, n=78) for the right and 1.18 (S.D. 0.47, n=70) for the left axillary arteries as compared to 0.60 (S.D. 0.11, n=77) for the right and 0.62 (S.D. 0.11, n=85) for the left axillary arteries in the control group. Intervals from diagnosis to follow-up were 0.5-3 years, 3-6 years and >6years, with a distribution of 96 (65%), 32 (22%) and 20 (13%) exams in the LV-GCA group and 29 (35%), 41 (50%) and 12 (15%) exams in the control group (excluding healthy controls), respectively. The optimal IMT cut-off value for the axillary arteries in patients with chronic LV-GCA was 0.87 mm with 75.0% sensitivity and 99.4% specificity (see figure 1). Sensitivity analysis (comparing patients with and without an involvement of the temporal artery at the time of diagnosis) validated this cut-off value. Conclusion An ultrasound IMT cut-off value for the axillary arteries can distinguish between patients with chronic LV-GCA and patients without chronic large vessel involvement. References [1] Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis2018;77:636-43. [2] Schafer VS, Juche A, Ramiro S, et al. Ultrasound cut-off values for intima-media thickness of temporal, facial and axillary arteries in giant cell arteritis. Rheumatology2017;56:1479-83. [3] De Miguel E, Beltran LM, Monjo I, et al. Atherosclerosis as a potential pitfall in the diagnosis of giant cell arteritis. Rheumatology2017;57:318-21. [4] Czihal M, Schrottle A, Baustel K, et al. B-mode sonography wall thickness assessment of the temporal and axillary arteries for the diagnosis of giant cell arteritis: a cohort study. Clin Exp Rheumatol2017;35Suppl 103:128-33. Disclosure of Interests Philipp Bosch: None declared, Christian Dejaco Speakers bureau: MSD, Pfizer, UCB, AbbVie, Roche, Novartis, Lilly, Celgene, Merck, Sandoz, Wolfgang A. Schmidt: None declared, Andreas Krause Consultant for: Pfizer, Speakers bureau: Pfizer, Kenny-Davis Schluter: None declared, Valentin S. Schafer: None declared

Background Acquisition and maintenance of competences by Health Professionals in Rheumatology (HPRs) is important to ensure the best care for people with rheumatic and musculoskeletal diseases (RMDs). HPRs’ competencies have never been systematically evaluated, nor international recommendations provided. A EULAR Task Force (TF) was formed for this purpose. Objectives To perform a systematic literature review (SLR) on the core competences of HPRs with a focus on nurses, physiotherapists (PT) and occupational therapists (OT) to inform the “EULAR recommendations for the generic core competences of Health Professionals in Rheumatology” Methods Thirteen main themes identified by the TF and translated into research questions, formed the basis of the SLR. Existing literature was systematically evaluated using the following databases (PubMed/Medline, Embase, Cochrane library, CENTRAL, Emcare, PsycINFO, Academic Search Premier, Web of Science, Google Scholar, ERIC and National Science Digital Library) from 1/1/1990 to 20/02/2018. Relevant search terms for competences, RMDs and HPRs were used. In addition, EULAR HPR national presidents were invited to share any documents describing HPRs’ competences. Inclusion criteria were: studies on competences or roles, knowledge, attitudes, skills or educational needs relevant for the management of people with RMDs, of HPRs in general or specifically of nurses, PTs or OTs, at post-graduate level. Exclusion criteria were: HPRs’ competences for children’s care or for concurring co-morbidities; extended roles of HPRs; a very specific clinical intervention or an intervention clearly attributable to only one profession or studies written in a language other than English or Dutch. All abstracts were screened to identify eligible studies for full text inclusion. The methodological quality of the studies was scored using appropriate tools (Table). Results From 591 unique references reviewed, 79 studies were included. Twenty studies addressed competences of multiple HPRs. The methodological quality of most papers was high to medium (Table). The identified studies underpinned a range of HPRs’ competences, including: communication skills, promotion of physical activity, basic knowledge about RMDs and education of patients and other health providers. Competences more relevant to specific professions (e.g musculoskeletal system examination skills for PTs and assessment of house and work environment for OTs) were also recorded. Heterogeneity in the HPR desired competences and practice across countries highlighted the need for further education of HPRs to acquire certain competences. Conclusion High-quality literature is available on the competences of HPRs for the management of people with RMDs. This literature supports the formulation of evidence-based recommendations for the core competences for HRPs by a EULAR Task Force. Disclosure of Interests None declared

Background:An increased prevalence of obstructive sleep apnea (OSA) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and partially in peripheral spondylarthritis (pSpA) has been noted and described for nearly two decades. Until now, there is no study yet on the occurrence of OSA in patients with these entities at the point of first diagnosis. Identifying and treating OSA could prove pivotal in improving cardiovascular risk and quality of life. Furthermore, clinicians require insights into whom to screen.Objectives:To assess the prevalence of OSA in early RA, PsA and pSpA and strategies for targeted screening.Methods:We performed a prospective study on patients with first diagnosis of RA, PsA or pSpA, who were screened for day sleepiness (assessed by the Epworth sleepiness scale) and tested for obstructive sleep disorders by out-of-center sleep apnea polygraphy (employing Embletta® MPR-PG devices) at the University Hospital of Bonn, Germany. Findings were assessed by three physicians, always including an attending physician responsible for the certified sleep laboratory.Results:A total of 22 patients with RA (52.38%), 15 with PsA (35.7%), and 5 (11.9%) with pSpA were included. Day sleepiness screening was unremarkable (ESS 15/h), eight (19.1%) for low-to-moderate sleep apnea (AHI 5-15/h) and 29 (69.1%) were unremarkable (AHI 2) was not associated with an AHI > 5/h (p≈0.63).Conclusion:From the point of screening, a number needed to screen of 8.4 (6.25 in the male, 17 in the female group), speaks in favor of overall cost-efficient screening for OSA in newly diagnosed male patients with arthritis diseases. A different study design, comparing early vs. established arthritis cohorts is necessary to assess the role of disease duration in the possible development of OSA.References:[1]Chung W-S, Lin C-L. Sleep disorders associated with risk of rheumatoid arthritis. Sleep Breath [Internet]. 2018 Dec 10 [cited 2018 Dec 11];22(4):1083–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29428977.[2]Vakil M, Park S, Broder A. The complex associations between obstructive sleep apnea and auto-immune disorders: A review. Med Hypotheses [Internet]. 2018;110:138–43. Available from: https://doi.org/10.1016/j.mehy.2017.12.004.[3]Wali S, Mustafa M, Manzar D, Bawazir Y, Attar S, Fathaldin O, et al. Prevalence of obstructive sleep apnea in patients with rheumatoid arthritis. J Clin Sleep Med. 2020.Table 1.Patient characteristicsTotal (n=42)RA (n=22)PsA (n=15)pSpA (n=5)AgeMedian (IQR)49 (36-61)58 (39-64)43 (30-55)39 (39-46)SexMale25 (59.5%)15 (68.2%)6 (40%)4 (80%)Female17 (40.5%)7 (31.8%)9 (60%)1 (20%)Obesity by BMI ()Normal weight/Underweight19 (45.2%)10 (45.5%)7 (46.6%)2 (40%)Overweight/Obesity23 (54.8%)12 (55.5%)8 (53.3%)3 (60%)ESS Score29 (69%)17 (77.3%)8 (53.3%)4 (80%)≥1013 (31%)5 (22.7%)7 (46.7%)1 (20%)AHI29 (69%)13 (59.1%)12 (80%)4 (80%)5-15/h8 (19.1%)6 (27.3%)1 (6.7%)1 (20%)>15/h5 (11.9%)3 (13.6%)2 (13.3%)0 (0%)RA – rheumatoid arthritis, PsA – psoriatic arthritis, pSpA – peripheral spondyloarthritis, IQR – interquartile range, BMI – body mass index, ESS – Epworth Sleepiness Scale, AHI – Apnea/Hypopnea IndexDisclosure of Interests:None declared

Background:Antinuclear antibodies (ANA) are serological markers for the presence of rheumatic diseases [1]. In some patients, a pattern can be detected in ANA immunofluorescence that resembles an anti-dense-fine-speckled-70 antibody [2]. This is detected less frequently in patients with connective tissue diseases (CTD) and is therefore often used as an exclusion criteria for a CTD [2]. To date, however, it is not clear how the presence of an anti-DSF70 autoantibody will reliably rule out CTDs.Objectives:To examine the degree to which CTDs can be excluded from either a positive test and whether there are discrepancies between patients with CTDs and a negative anti-DSF70 test and those with CTDs and a positive anti-DSF70 test.Methods:We analyzed data of 460 patients who were tested for the presence of the DSF70 antibody at the University Hospital Bonn, Germany. Patients were examined with regard to clinical symptoms and signs, type of disease, type of CTD, fulfillment of the classification criteria for the particular CTD, DSF70 antibodies, other autoantibodies and ANA titer. Gold standard for presence of a CTD was the diagnosis of the treating rheumatologist.In addition to variations between patients with CTD and positive or negative DSF70 antibodies, specificity, sensitivity and positive predictive value were calculated for different ANA titers.Results:Of the 460 patients, 79.8% were female and 182 were diagnosed with a CTD. 354 patients (77.0%) were tested negative, 81 (17.6%) positive and 25 (5.4%) had a borderline anti-DSF70 autoantibody result.We identified 21 patients with a positive test result in the presence of a CTD, which accounts for 25.9% of all anti-DSF70 autoantibody positive tested patients.We found no significant differences in DSF70-positive patients with CTD in regard to age, gender, symptoms, clinical signs and also disease-specific antibodies compared to patients with negative DSF70 status and present CTD.Of the 21 DSF70-positive patients with CTD, 12 (57.1%) were tested for the presence of disease-specific autoantibodies. Specific autoantibodies could be detected in all of the tested patients with systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome and mixed connective tissue disease.DSF70 autoantibodies had a specificity of 86.8%, a sensitivity of 26.9% and a positive predictive value of 68.2% at an ANA titer of ≥1:160, with respect to the absence of a connective tissue disease.Table 1.Sensitivity, specificity and positive predictive value of anti-DSF70 autoantibody in different ANA titers (borderline patients excluded)a) ANA-Titer ≥ 1:80N=362No present CTDPresent CTDDSF70 positive5221DFS70 negative145144Sensitivity: 26.4%Specificity: 87.3%Positive predictive value= 71.2%b) ANA-Titer ≥ 1:160N=326No present CTDPresent CTDDSF70 positive4521DSF70 negative122138Sensitivity: 26.9%Specificity: 86.8%Positive predictive value= 68.2%c) ANA-Titer ≥ 1:640N=167No present CTDPresent CTDDSF70 positive1714DSF70 negative4888Sensitivity: 26.2%Specificity: 86.3%Positive predictive value= 54.8%Conclusion:Autoantibodies to DSF70 often occur in CTD patients and are therefore not a valid exclusion criteria for a CTD. We observed no CTD in 68.2% of patients who were tested positive. Thus, in difficult situations, the DSF70 test may be helpful and the additional exclusion of other autoantibodies may render CTD even less probable.References:[1]Mahler M, Fritzler MJ. Epitope specificity and significance in systemic autoimmune diseases: Epitope specificity. Ann N Y Acad Sci. 2010;1183(1):267-287.[2]Mahler M, Hanly JG, Fritzler MJ. Importance of the dense fine speckled pattern on HEp-2 cells and anti-DFS70 antibodies for the diagnosis of systemic autoimmune diseases. Autoimmun Rev. 2012;11(9):642-645.Disclosure of Interests:Louisa-Marie Mockenhaupt: None declared, Ramona Dolscheid-Pommerich: None declared, Charlotte Behning: None declared, Birgit Stoffel-Wagner: None declared, Peter Brossart: None declared, Valentin Schäfer Speakers bureau: AbbVie, Novartis, BMS, Chugai, Celgene, Medac, Sanofi, Lilly, Hexal, Pfizer, Janssen, Roche, Schire, Onkowissen, Royal College London, Consultant of: Novartis, Chugai, AbbVie, Celgene, Sanofi, Lilly, Hexal, Pfizer, Amgen, BMS, Roche, Gilead, Medac, Grant/research support from: Novartis, Hexal, Lilly, Roche, Celgene, Universität Bonn

Background:The clinical differentiation between gout, osteoarthritis (OA), and calcium pyrophosphate deposition disease (CPPD) still remains a hurdle in daily practice without imaging or arthrocentesis. Although a plethora of clinical data exists, reliable predictor biomarkers for all but gout are still missing.Objectives:To explore an association between common physical examination, ultrasound and laboratory findings and gout, OA, and CPPD, which can in turn provide reliable diagnostic predictions.Methods:277 patients were retrospectively analysed using ANOVA with Scheffe’s post hoc tests and conditional inference trees regarding biomarkers such as age, sex, body mass index, hypertension, renal status, cumulative affected joint size, number of afflicted joints, double contour sign, intracartiliginous double contour sign, degree of vascularization on ultrasound (DoV), uric acid, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, and leucocyte count. Simple linear regressions were carried out to explore associations between increased inflammatory parameters and the above-mentioned biomarkers. Statistically significant associations were defined as p values < 0.05.Results:The male sex was associated with gout (p value < 0.05 vs CPPD and < 0.05 vs OA). OA affected younger patients than CPPD (mean 64.5 vs 73.1 years, p < 0.05). Hypertension was correlated with gout (p < 0.05) and CPPD (p < 0.05), impaired renal status with gout when compared to OA (p < 0.05) but not compared to CPPD (p 0.21). A higher number of involved joints was associated with gout (mean 2.2 joints) compared to OA (1.0, p < 0.05) and CPPD (1.6, p 0.01). The double contour sign was not able to differentiate gout and CPPD with a sensitivity/specificity of 71%/55% for gout and 59%/39% for CPPD. The intracartilaginous double contour sign was specific for CPPD (99%) but with a low sensitivity of 26%. DoV was significantly associated with gout (vs OA, p < 0.05) and CPPD (vs OA, p < 0.05). Unsurprisingly, uric acid was associated with gout while ESR and CRP were increased in gout and CPPD, but not in OA. Some associations were statistically significant but arguably clinically unimportant. Conditional inference trees were able to exclude OA (specificity 97.5%) and CPPD (specificity 94.0%) as possible differentials based on just uric acid, CRP, hypertension, and sex, and diagnose gout with a sensitivity of 95.1%, summarized in Figure 1. Linear regressions demonstrated an elevated CRP response in people suffering from type II diabetes, higher cumulative joint points score, number of affected joints, as well as elevated uric acid, ESR, and leucocyte count.Figure 1.Conditional inference tree using unbiased recursive partitioning to reliably differentiate between gout, osteoarthritis, and calcium pyrophosphate deposition disease.Conclusion:Gout can be reliably diagnosed, simultaneously excluding OA and CPPD as differential diagnoses by conditional inference trees using just four biomarkers. A correlation between inflammatory reaction severity based on CRP levels was found in patients suffering from type II diabetes, more or larger joint involvement and elevated uric acid levels. The double contour sign remains a questionable differentiator between gout and CPPD with a sensitivity/specificity of 71%/55% for gout and 59%/39% for CPPD, similar to findings reported by Löffler et al (1) with a sensitivity/specificity of only 64%/52% for gout.References:[1]Löffler C, Sattler H, Peters L, Löffler U, Uppenkamp M, Bergner R. Distinguishing gouty arthritis from calcium pyrophosphate disease and other arthritides. J Rheumatol 2015; 42(3):513–20.Disclosure of Interests:Dmitrij Kravchenko Shareholder of: Pfizer, Raoul Bergner: None declared, Charlotte Behning: None declared, Valentin Schäfer Speakers bureau: AbbVie, Novartis, BMS, Chugai, Celgene, Medac, Sanofi, Lilly, Hexal, Pfizer, Janssen, Roche, Schire, Onkowissen, Royal College London, Consultant of: Novartis, Chugai, AbbVie, Celgene, Sanofi, Lilly, Hexal, Pfizer, Amgen, BMS, Roche, Gilead, Medac, Grant/research support from: Novartis, Hexal, Lilly, Roche, Celgene, Universität Bonn.

Background:The European League Against Rheumatism (EULAR) recommends using ultrasound (US) in patients with rheumatoid arthritis and psoriatic arthritis in diagnosis (1). In addition, US examination is crucial for detecting enthesitis in the above mentioned rheumatic diseases. However, abnormal findings on US may also occur in healthy individuals as indicated by recent studies focusing on small joints like metacarpophalangeal joint, metatarsophalangeal joint or the elbow. (2,3)Ultrasound assessment of large joints in healthy individuals has not been extensively studied so far, causing a lack of information concerning normal values in musculoskeletal US examination.Objectives:The purpose of this study was to determine the prevalence of joint effusion, hyperperfusion of the synovia and enthesitis in large and medium-sized joints of healthy individuals.Methods:Ultrasound assessment of shoulder, elbow, wrist, hip, knee and ankle joints as well as corresponding entheseal sites including the Achilles tendon and the plantar aponeurosis was performed in healthy individuals below the age of 30 years. Additionally, participants filled out a survey on their physical activity level, underwent a bioelectrical impedance analysis (BIA) and conducted a supervised weight training to determine their training volume. Prevalence of US findings was calculated, and a binary logistic regression model was applied to determine the association between the present findings and sex, age, handedness, hours of sports activity per week, BMI, amount of skeletal muscle mass (SMM) or training volume of strength training.Results:We included 51 healthy individuals with a mean age of 23.7 years, 52.9% were female with a mean BMI of 22.5 kg/m2. Ultrasound examination detected joint effusion in one joint in 25.5% (n=13), 29.4% (n=15) showed effusion in two of twelve examined joints. Joint effusion in three, four and five joints was detected in 9.8% (n=5), 3.9% (n=2) and 3.9% (n=2) of the cases, respectively. In 27.5% (n=14) of the individuals no joint effusion was observed. The most frequently affected joint was the elbow joint. Synovial hyperperfusion was not detected in any participant. Enthesitis was observed in one, two and three examined entheseal sites in 19.5% (n=10), 5.9% (n=3) and 2% (n=1), respectively. In 72% (n=37) of the examined individuals no pathology of the entheseal sites was found. Hyperperfusion presented to be the most frequent pathology observed in enthesitis (23%), followed by calcification (6%).Binary logistic regression model demonstrated a significant association between reported hours of sports activity per week and the prevalence of effusion in the knee (p = 0.017). The odds of joint effusion in the knee increased with the hours of sports activity by 34.1% (Exp(B)= 1.341, 95%-CI(1.054, 1.705)). Additionally, the odds of enthesitis in any entheseal site increased with BMI (p= 0.015, Exp(B) = 1.407, 95%-CI(1.068, 1.852).Binary logistic regression model did not show any significant association between sex, age, handedness, amount of SMM or training volume of strength training and the prevalence of joint effusion or enthesis pathology in the examined participants.Conclusion:Joint effusion in large and mid-sized joints as well as enthesitis are not only detected in patients with rheumatic diseases but also in healthy individuals. Hours of sports activity and BMI have a significant association with the findings and should be considered during ultrasound examination.References:[1]Colebatch AN, Edwards CJ, Østergaard M, van der Heijde D, Balint PV, D’Agostino M-A, u. a. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. Juni 2013;72(6):804–14.[2]Padovano I, Costantino F, Breban M, D’Agostino MA. Prevalence of ultrasound synovial inflammatory findings in healthy subjects. Ann Rheum Dis. Oktober 2016;75(10):1819–23.[3]Schäfer VS, Recker F, Vossen D, Ge I, Matuschek E, Hartung W. Prevalence of Elbow Joint Arthritis and Enthesitis in Rheumatoid Arthritis. 2020;11.Disclosure of Interests:Julia Konstanze Schreiner: None declared, Dennis Scheicht: None declared, Pantelis Karakostas: None declared, Charlotte Behning: None declared, Peter Preuss: None declared, Peter Brossart: None declared, Valentin Schäfer Speakers bureau: AbbVie, Novartis, BMS, Chugai, Celgene, Medac, Sanofi, Lilly, Hexal, Pfizer, Janssen, Roche, Schire, Onkowissen, Royal College London, Consultant of: Novartis, Chugai, AbbVie, Celgene, Sanofi, Lilly, Hexal, Pfizer, Amgen, BMS, Roche, Gilead, Medac, Grant/research support from: Novartis, Hexal, Lilly, Roche, Celgene, Universität Bonn

Background:Hypophosphatasia (HPP) is a genetic disease caused by one or more mutations in the alkaline phosphatase (ALP) gene, which encodes tissue-specific ALP and affects the mineralization process. Accordingly, arthralgia, fractures, and dental abnormalities have been reported in adults, and fatal courses in children. This metabolic disorder is commonly misdiagnosed with other more prevalent bone diseases due to its low prevalence and lack of recognition (i.e. chrondrocalcinosis). However, no epidemiological studies on the prevalence of HPP in the rheumatological patient population have been available to date.Objectives:To identify the prevalence of HPP in rheumatological patients screened for persistent low levels of ALP and association with mutations in the ALP gene.Methods:All adult rheumatology patients were screened for pathological low levels of ALP (< 35 IU/L) between January 1, 2017 and June 30, 2019 at the Department of Rheumatology, Clinic of Internal Medicine III, University Hospital Bonn, Germany. Medical files of patients with pathological low ALP levels were then reviewed for clinical signs and symptoms as well as results of genetic testing for HPP (full sequencing using Next Generation Sequencing).Results:In total, 2,289 rheumatology patients were screened for low ALP levels. In 60 patients (2.62 %), pathological low ALP levels were identified, while in 30 of these (1.31 %), persistent low ALP levels were detected. In 19 of the 30 patients, genetic tests for ALPL gene mutations were done. Seven out of 19 patients (36.84 %) had HPP-related symptoms (fracture, dental abnormalities) with normal bone densitometry, while four of these patients (21.05 %) had a history of fracture and three patients (15.78 %) showed dental abnormalities. In addition to the typical HPP signs and symptoms, 13 patients (68.42%) showed mutations in the ALPL gene. One of the ALP mutations was found to be a novel genetic variant, classified as pathological. Interestingly, no association with chondrocalcinosis was detected.Conclusion:In summary, it can be concluded that HPP is an under-diagnosed condition with a higher proportion of affected rheumatologic patients than previously thought (at least 0.56 percent of rheumatologic patients vs. 0,01 percent in a spanish healthy population). If we replicate these numbers for the german population (83 million, 5 percent of whom suffer from rheumatic conditions) the yield is approximately 4.15 million. This possibly indicates that 23,240 potential cases of HPP are currently not diagnosed. Therefore, implementation of a protocol in clinical practice to prevent underdiagnosis of HPP and to treat this disease appropriately is essential.References:[1]García-Fontana C, Villa-Suárez JM, Andújar-Vera F et al (2019) Epidemiological, Clinical and Genetic Study of Hypophosphatasia in A Spanish Population: Identification of Two Novel Mutations in The Alpl Gene. Sci Rep. https://doi.org/10.1038/s41598-019-46004-2[2]Mornet E, Yvard A, Taillandier A et al (2011) A molecular-based estimation of the prevalence of hypophosphatasia in the European population. Ann Hum Genet 75:439–445. https://doi.org/10.1111/j.1469-1809.2011.00642.xFigure 1.Flow chart of identification of potential hypophosphatasia (HPP) patients from an adult rheumatology population. Threshold alkaline phosphatase < 35 IU/L at 37`C. ALP: alkaline phosphataseDisclosure of Interests:Pantelis Karakostas: None declared, Ramona Dolscheid-Pommerich: None declared, Moritz Hass: None declared, Peter Brossart: None declared, Valentin Schäfer Speakers bureau: AbbVie, Novartis, BMS, Chugai, Celgene, Medac, Sanofi, Lilly, Hexal, Pfizer, Janssen, Roche, Schire, Onkowissen, Royal College London, Consultant of: Novartis, Chugai, AbbVie, Celgene, Sanofi, Lilly, Hexal, Pfizer, Amgen, BMS, Roche, Gilead, Medac, Grant/research support from: Novartis, Hexal, Lilly, Roche, Celgene, Universität Bonn.

Background:Over the past few decades, technological advances in both ultrasound (US) and the application of telemedicine have been made [1]. Medical education has shifted to online classes during the COVID-19 pandemic, creating challenges in adequate training of US.Objectives:In the context of the current COVID-19 pandemic and the discontinuation of traditional classroom teaching, a tele-didactic US course for undergraduate medical students was developed. This study is examining the educational outcome of a new digital US course of the abdomen, thorax and the thyroid gland with the implementation of a modern portable US system.Methods:A tele-guided US course was established between April 1st and June 20th, 2020, at the University Hospital in Bonn, Germany. Students completed pre-and post-course surveys and underwent six US organ modules. Each module took place in a flipped-classroom concept including a digital learning platform. An objective structured assessment of US skills (OSAUS) [2] was implemented as final exam. Further, US images of the course and exam were rated by the Brightness Mode Quality Ultrasound Imaging Examination Technique (B-QUIET) [3]. Achieved points in image rating were compared to the OSAUS exam and survey results.Results:A total of 15 medical students were enrolled. There was a significant increase in self-assessed theoretical and practical ability (p < 0.001). Students achieved an average score of 154.5 (SD ± 11.72) out of 175 points (88.29%) in OSAUS, which corresponded to the image rating using B-QUIET and self-assessment data obtained in surveys. Interrater analysis of US images showed a favorable agreement with an ICC (2,1) of 0.895 (95% confidence interval 0.858 < ICC < 0.924).Conclusion:US training via teleguidance should be considered in medical education. Our pilot study demonstrates the feasibility of this concept that can be used in the future to improve US training of medical students even during a pandemic. The digital implementation with an affordable, portable point-of-care-US device could be an incredible opportunity to expedite US training worldwide.References:[1]Law J, Macbeth PB. Ultrasound: from Earth to space. Mcgill J Med 2011; 13(2): 59 [PMID: 22399873][2]Tolsgaard MG, Todsen T, Sorensen JL, et al. International multispecialty consensus on how to evaluate ultrasound competence: a Delphi consensus survey. PLoS One 2013; 8(2): e57687[https://doi.org/10.1371/journal.pone.0057687][PMID: 23469051][3]Bahner DP, Adkins EJ, Nagel R, Way D, Werman HA, Royall NA. Brightness mode quality ultrasound imaging examination technique (B-QUIET): quantifying quality in ultrasound imaging. J Ultrasound Med 2011; 30(12): 1649–55[4][https://doi.org/10.7863/jum.2011.30.12.1649][PMID: 22124000]Figure 1.Implementation of the digital ultrasound course conceptClassroom setting is displayed, demonstrating simultaneous screen transmission of ultrasound (US) and camera images. A: The peer tutor’s camera image is shared with the students while demonstrating the US examination, B: At the same time the tutor’s mobile phone screen is shared with the students in order to visualize the US image acquisition, C: Students performing the US examination on their own, D: Example of a worksheet, which had to be completed within the app and was stored along with the US images in the cloudDisclosure of Interests:None declared

Aims: To assess intima-media thickness (IMT) changes measured by ultrasound in axillary arteries of giant cell arteritis (GCA) patients over time and to calculate an ultrasound cut-off value for the diagnosis of chronic axillary artery involvement in patients with longstanding GCA. Methods: Ultrasound of both axillary arteries was performed in 109 GCA patients at time of diagnosis and at several follow-up visits and in 40 healthy controls (HCs). IMT determined at the prospective follow-up visit was compared between GCA patients with (axGCA) and without (non-axGCA) vasculitis of axillary arteries at baseline, as well as with HCs. Changes in IMT were depicted. Receiver operating characteristics were performed for cut-off calculations. Inter-/intra-rater agreement was evaluated using stored images and intraclass correlation coefficient (ICC). Results: Seventy-three patients were in the axGCA and 36 in the non-axGCA group. Pathological IMT of axillary arteries (axGCA) declined in the first 18 months of treatment by −0.5 mm, (range −2.77 to 0.50), independent of age and gender. Median IMT, after median disease duration of 48 months (16–137), was 0.90 mm (0.46–2.20) in axGCA and 0.60 mm (0.42–1.0) in the non-axGCA group pooled with HCs. An IMT of 0.87 mm was highly specific (specificity 96%, sensitivity 61%) for diagnosis of chronic axGCA. Intra-rater and inter-reader agreement of ultrasound images were good [ICC 0.96–1.0 (three readers) and 0.87, respectively]. Conclusion: Pathological IMT of the axillary artery declined under treatment. An IMT of 0.87 mm is highly specific for diagnosis of chronic vasculitis of axillary arteries in long-standing GCA patients.