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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 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

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.

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.

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.

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.

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 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: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: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.

Spinal epidural lipomatosis (SEL) of the thoracic and lumbar spine is a rare entity, which leads to compression of the spinal canal. The exact pathogenesis is still unknown. It most commonly occurs in patients with long-term exogenous or endogenous glucocorticoid excess or morbid obesity but there are also idiopathic forms. The symptoms depend on the severity of the SEL and can manifest as clinically asymptomatic, non-specific back pain, radiculopathy up to spinal cord compression. The diagnosis is usually achieved by magnetic resonance imaging (MRI) of the affected spinal segments. The treatment varies between discontinuation of glucocorticoids, weight reduction up to multisegmental decompressive laminectomy. The following case report presents the findings of SEL in a patient with steroid-dependent Jo-1 antibody syndrome and provides a current literature review on this rare disease.

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.

Background:Immune checkpoint inhibitors (ICIs) have improved cancer therapy and especially clinical outcomes for patients with many malignancies [1]. ICIs lead to a higher immune system activity and subsequent attack of tumor cells. However, this effect can cause rheumatological immune related adverse events (rh-irAE), which have not yet been extensively studied.Objectives:To determine the prevalence and type of rh-irAE in patients treated with ICIs. Additionally, our study focused on duration, severity and therapy of rh-irAE as well as the correlation between tumor response rate and patients with or without rh-irAE.Methods:We analysed 437 patients between January 2014 and October 2019, treated with ipilimumab (anti-CTLA-4) and/ or nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1) at the Department of Oncology, Hematology and Rheumatology at the University Hospital in Bonn, Germany.Results:Of the 437 patients, 260 (60%) were males, 177 (40%) were females with a mean age of 64 years (SD ± 14) at the beginning of the ICI-therapy. 152 patients (34.8%) displayed at least one irAE.We identified 20 patients (4.6%) with a minimum of one rh-irAE due to ICI-therapy, seven of those had a pre-existing rheumatological disease. Those 20 patients were initially treated for melanoma, lung cancer, head and neck tumor and gastrointestinal carcinoma. Rh-irAE occurred in one patient (2.6%) with ipilimumab, in nine patients (4.8%) with nivolumab, in nine patients (5.7%) with pembrolizumab and in one patient (1.9%) with a combination of ipilimumab and nivolumab.Arthralgia developed most frequently in nine of the 20 patients (45%). Arthritis and myositis occurred with equal frequencies, in three cases each (3 patients, 15%). Furthermore, three of the 20 patients (15%) developed a psoriatic arthritis and one patient (5%) osteoarthritis. The time to the first rh-irAE after exposure to ICIs was in median 100 days (IQR 45 – 406 days). Most rh-irAE were classified as moderate severe (CTCAE [Common Terminology Criteria of Adverse Events] grade 2: 55%).15 patients (75%) were treated with systemic corticosteroids. In three cases (15%) additional therapy with methotrexate and in one patient (5%) with tocilizumab was required. Other therapies including non-steroidal anti-inflammatory drugs and opioids were also used in eight patients. Even though patients benefited from ICI treatment, therapy had to be discontinued in nine of them (45%).Interestingly, patients with rh-irAE had a significantly higher tumor response rate compared to patients without any irAE (95% vs. 33%; pTable 1.Independent risk factors of IFI in patients with SLEaCandidiasisCryptococcosisAspergillosisHR (95% CI)PvalueHR (95% CI)PvalueHR (95% CI)PvalueAge>501.77 (1.27-2.47)Diabetes mellitus1.65 (1.16-2.35)0.006End-stage renal disease1.76 (1.29-2.41)Stroke1.77 (1.26-2.47)1.96 (1.09-3.53)0.024Mycophenolate mofetil2.72 (1.60-4.61)4.02 (1.32-12.26)0.015Cyclosporin4.94 (1.61-15.10)0.005Cyclophosphamide1.50 (1.07-2.10)0.019Intravenous steroid28.19 (21.17-37.52)63.51 (36.10-111.71)34.80 (15.09-80.24)aAll factors withPCI, confidence interval; HR, hazard ratio.Figure 1.Incidence rate and incidence rata ratio of invasive fungal infectionFigure 2.Kaplan-Meier curve of invasive fungal infection-free status in SLE versus non-SLE group.Conclusion:Our results show, that rh-irAE occur under ICI-therapy and in patients with higher tumor response. However, they are not the most frequent irAE after ICI exposure: 10.2% of all irAE were rheumatological (22 rh-irAE cases in 20 patients of a total of 216 irAE cases in 152 patients). As the use of ICIs is increasing for different malignancies the incidence of rh-irAE can be expected to increase.References:[1] Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade.Science. 2018;359(6382):1350-1355. doi:10.1126/science.aar4060[2] Spain L, Diem S, Larkin J. Management of toxicities of immune checkpoint inhibitors.Cancer Treat Rev. 2016;44:51-60. doi:10.1016/j.ctrv.2016.02.001AcknowledgmentsDisclosure of Interests:None declared

Background:Giant cell arteritis (GCA) is the most common form of systemic vasculitis affecting people aged 50 years and older.1Although it is known, that GCA often coexists with polymyalgia rheumatica (PMR)2, prevalence of GCA in consecutive patients with PMR has not been investigatedObjectives:To prospectively examine the prevalence of GCA in consecutive patients with PMR by vascular ultrasound (US).Methods:Patients with newly diagnosed PMR fulfilling the ACR /EULAR classification criteria3were included. Vascular US examination of the extracranial arteries typically involved in GCA, such as axillary arteries, vertebral arteries, common carotid arteries, superficial temporal arteries with both frontal and parietal branches, occipital arteries, facial arteries and the central retinal arteries was performed in all PMR patients. Diagnosis of GCA was made, if intima-media thickness (IMT) was above respective cut-off values.4Results:Fifty patients with diagnosis of PMR underwent vascular US. Twenty-three patients (46%) had PMR without GCA (PMR-group). The mean age in this group was 71 years (SD ± 10) with seventeen (73%) females. In twenty-seven PMR patients (54%) GCA was diagnosed (GCA-PMR group); the mean age in this group was 74 years (SD ± 9) with ten (37%) females respectively. Mean C-reactive protein (CRP) values were 29.4 mg/l (SD±24.5) in the PMR-group and 52.2 mg/l (SD±43.2) in the GCA-PMR-group. Although different mean values between the PMR-group and the GCA-PMR-group were observed, CRP values did not differ significantly between the two groups (p = 0.1432). Ten (37%) patients of the GCA-PMR group did not have GCA symptoms and diagnosis of GCA was only determined by ultrasound examination. Symptoms and numbers of patients with respective symptoms are depicted in Table 1 and 2.Table 1.Symptoms and signs in both groupsSymptoms and signsGroupPMR-groupGCA-PMR-groupMorning stiffness22 (95%)23 (85%)≥1 shoulder with synovits or bursitis trochanterica12 (52%)13 (48%)≥1 shoulder or hip with synovitis or bursitis11 (48%)14 (51%)hip pain23 (100%)23 (85%)No other joints affected22 (95%)26 (96%)PMR-group: patients with diagnosis of polymyalgia rheumatica onlyGCA-PMR-group: patients with diagnosis of polymyalgia rheumatic and giant cell arteritisConclusion:Prevalence of GCA in patients with PMR in our cohort was 54%. Ten (37%) patients with GCA and PMR did not have any GCA symptoms. Performing vascular US in patients with PMR can be useful to diagnose a clinical inapparent GCA. Prompt onset of the respective therapy could prevent complications of GCA and improve disease outcome.References:[1]Warrington KJ, Matteson EL. Management guidelines and outcome measures in giant cell arteritis (GCA). Clin Exp Rheumatol 2007;25:137–41[2]Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. The Lancet 2008;372:234–45.[3]Dasgupta B, Cimmino MA, Kremers HM, et al. 2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheum 2012;64:943–54.[4]Schäfer VS, Juche A, Ramiro S, Krause A, Schmidt WA. Ultrasound cut-off values for intima-media thickness of temporal, facial and axillary arteries in giant cell arteritis. Rheumatology (Oxford) 2017;56:1479–83.Table 2.Number of patients in each group with symptoms of giant cell arteritisSymptomsGroupPMR-groupGCA-PMR-groupVisual symptoms2 (9%)8(30%)Headache2 (9%)9 (33%)Jaw claudication4 (18%)10 (38%)Scalp tenderness0 (0%)5 (19%)No GCA symptoms15 (65%)10 (37%)PMR-group: patients with diagnosis of polymyalgia rheumatica onlyGCA-PMR-group: patients with diagnosis of polymyalgia rheumatic and giant cell arteritisDisclosure of Interests:None declared

Background:Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) often coexist.1The role of modern ultrasound in diagnosis of GCA as well as PMR is well known.2To date it is unknown, whether patients with GCA and PMR have a different vasculitis pattern in ultrasound (US) examination than patients with GCA only.Objectives:To prospectively identify differences in vasculitis patterns in consecutive patients with newly diagnosed GCA and PMR compared to newly diagnosed GCA patients without PMR.Methods:US examination of the arteries typically affected in GCA, such as axillary arteries, vertebral arteries, superficial temporal arteries with both frontal and parietal branches and facial arteries was performed in patients with GCA and PMR (GCA-PMR-group) as well as in patients with GCA only (GCA-group) at time of first diagnosis. Arteries were defined as pathological, if measured intima-media-thickness by US was above respective cut-off values.3Results:The GCA-PMR-group consisted of 27 patients, the GCA-group of 18 patients. In the GCA-PMR-group, a total of 206 arteries were affected, while in the GCA-group 131 arteries were affected. Mean age and gender distribution was 74 years (SD± 9) with 10 (37%) females in the GCA-PMR-group and 76 years (SD± 9) with 10 (55%) females in the GCA-group. Median values of C-reactive protein (CRP) were 57.2 (IQR 31.7-75.7) in the GCA-group and 48.3 (IQR 17.5- 79.9) in the GCA-PMR-group, no significance was observed (p= 0.3577). Mean number of affected arteries per patient was 7.63 and 7.28 in the GCA-PMR-group and GCA-group, respectively. Altogether, no significant difference in vascular pattern between the two groups was observed. Exact numbers, distribution and IMT-values for all measured arteries are depicted in table 1.Conclusion:In our cohort, we did not observe a significant difference in vascular patterns between patients with GCA and PMR and GCA only patients.References:[1]Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. The Lancet 2008;372:234–45.[2]Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis 2018;77:636–43.[3]Schäfer VS, Juche A, Ramiro S, Krause A, Schmidt WA. Ultrasound cut-off values for intima-media thickness of temporal, facial and axillary arteries in giant cell arteritis. Rheumatology (Oxford) 2017;56:1479–83.Disclosure of Interests:None declared

Background:Giant cell arteritis (GCA) is the most common form of systemic vasculitis in patients aged 50 years and older.1Visual symptoms such as amaurosis, diplopia, temporary or permanent visual field loss secondary to optic nerve ischemia are common manifestations.2The value of vascular ultrasound of extra-ocular vessels in diagnosing GCA is well established.3However, the role of transocular ultrasound of the central retinal artery in GCA patients has not yet been established.Objectives:To identify changes in flow velocities of the central retinal artery in GCA patients with visual symptoms and controls with transocular high resolution ultrasound.Methods:Prospective analysis of GCA patients with visual symptoms and controls. Ultrasound of the central retinal artery was performed in 18 newly diagnosed consecutive GCA patients with visual symptoms (GCA-group) and 25 controls without ocular pathology. Visual symptoms included amaurosis, diplopia and temporary or permanent visual field loss. For each eye, peak systolic values (PS) and end diastolic values (ED) were recorded. Furthermore, the resistance index of each central retinal artery was measured.Results:Twenty-one of 36 eyes of 18 GCA patients were affected. Therefore 21 central retinal were measured. The control group consisted of 50 central retinal arteries of 25 eye-healthy individuals. The mean age and gender distribution of the GCA-group were 75.6 years (SD± 8.1) with eight females (44 %) and 67 years (SD± 8.9) with twelve females (48%) in the control group. The mean flow velocity of the central retinal artery was PS 12.2 cm/s (SD± 3.5) and ED 3.7 cm/s (SD± 1.2) in the GCA group and PS 14.4 cm/s (SD± 3.2) and ED 5.1 cm/s (SD± 1.6) in the control group. The mean RI was 0.9 (SD± 0.3) in the GCA group and 0.8 (SD± 0.3) in the control group. Mean reduction in flow velocity in the GCA-group was PS 2.1 cm/s (p= 0.039) and ED 1.4 (p= 0.0004) cm/s, while the RI was increased by 0.14 (p= 0.077). The results for PS and ED measurements were statistically significant, while the results for RI were not significant.Conclusion:In GCA patients with ocular symptoms, a reduction of flow velocities of the central retinal artery compared to the eye-healthy control group was found. Results for PS and ED were significant. There seems to be a trend for decreased flow velocities in coexistence with visual symptoms in patients with GCA.References:[1]Warrington KJ, Matteson EL. Management guidelines and outcome measures in giant cell arteritis (GCA). Clin Exp Rheumatol 2007;25:137–41.[2]Chean CS, Prior JA, Helliwell T, et al. Characteristics of patients with giant cell arteritis who experience visual symptoms. Rheumatol Int 2019;39:1789–96.[3]Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis 2018;77:636–43Figure 1.Transocular ultrasound of an affected eye in giant cell arteritis with reduced flow velocities and increased resistance index.Disclosure of Interests:None declared

Background:Differentiation of gout and calcium pyrophosphate deposition disease (CPPD) is sometimes difficult as patients often present with a similar clinical picture. Arthrocentesis and subsequent polarization microscopy (PM) remains the gold standard but novel diagnostic approaches such as non-invasive dual energy computed tomography (DECT) have recently been validated for gout. Currently, limited data is available on DECT in patients with CPPD.Objectives:To analyse the diagnostic impact of DECT in gout and CPPD when compared to the gold standard of PM. We further compared the results of PM to ultrasound (US), conventional radiographs (CR), and suspected clinical diagnosis (SCD). Additionally, 15 laboratory parameters were analysed.Methods:Twenty-six patients diagnosed with gout (n = 18) or CPPD (n = 8) who received a DECT and underwent arthrocentesis were included. Two independent readers assessed colour coded, as well as 80 and 120 kV DECT images for signs of monosodium urate (MSU) crystals or CPP deposition. US and CR from the patient’s initial visit along with the SCD were also compared to PM. US examinations were performed by certified musculoskeletal ultrasound specialists. The association of up to 15 laboratory parameters such as uric acid, thyroid stimulating hormone, and C-reactive protein (CRP) with the PM results was analysed.Results:Sensitivity of DECT for gout was 67% (95% CI 0.41-0.87) with a specificity of 88% (95% CI 0.47-1.0). Concerning CPPD, the sensitivity and specificity of DECT was 63% (95% CI 0.25-0.91) and 83% (95% CI 0.59-0.96) respectively. US had the highest sensitivity of 89% (95% CI 0.65-0.99) with a specificity of 75% (95% CI 0.35-0.97) for gout, while the sensitivity and specificity for CPPD were 88% (95% CI 0.47-1.0) and 89% (95% CI 0.65-0.99) respectively. The SCD had the second highest sensitivity for gout at 78% (95% CI 0.52-0.94) with a comparable sensitivity of 63% (95% CI 0.25-0.92) for CPPD. Uric acid levels were elevated in 33% of gout patients and 25% of CPPD patients. While elevated CRP levels were observed in 59% of gout patients and in 88% of CPPD patients, none of the 15 analysed laboratory parameters were found to be significantly linked.Conclusion:DECT provides a non-invasive diagnostic tool for gout but might have a lower sensitivity than suggested by previous studies (67% vs 90%1). DECT sensitivity for CPPD was 63% (95% CI 0.25-0.91) in a sample group of eight patients. Both US and the SCD had higher sensitivities than DECT for gout and CPPD. Further studies with larger patient cohorts are needed in order to determine the diagnostic utility of DECT in CPPD.References:[1]Bongartz, Tim; Glazebrook, Katrina N.; Kavros, Steven J.; Murthy, Naveen S.; Merry, Stephen P.; Franz, Walter B. et al. (2015): Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study. InAnnals of the rheumatic diseases74 (6), pp. 1072–1077. DOI: 10.1136/annrheumdis-2013-205095.Disclosure of Interests:None declared

Objectives: To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise.Methods: Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise.Results: Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The 'halo' and 'compression' signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the 'halo' sign and the 'compression' sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts.Conclusions: The 'halo' and the 'compression' signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent.

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

Objective To evaluate the intima-media thickness (IMT) of arteries involved in GCA for determining cut-off values. Methods Forty newly diagnosed GCA patients in a fast-track GCA clinic and 40 age- and sex-matched controls were included. IMT measurement was performed at or within 24 h after diagnosis. The common superficial temporal arteries with their frontal and parietal branches and the facial arteries were bilaterally examined with a 10-22 MHz probe and the axillary artery with a 6-18 MHz probe. Receiver operating characteristics analysis was performed for estimating cut-off values. Results The mean age was 72 years (s.d. 9) and 68% were females. In the control group, IMT was 0.23 mm (s.d. 0.04), 0.19 mm (s.d. 0.03), 0.20 mm (s.d. 0.03), 0.24 mm (s.d. 0.05) and 0.59 mm (s.d. 0.10) for the common superficial temporal arteries, the frontal and parietal branches, the facial arteries and the axillary arteries, respectively. In vasculitic segments of GCA patients, IMT was 0.65 mm (s.d. 0.18), 0.54 mm (s.d. 0.18), 0.50 mm (s.d. 0.17), 0.53 mm (s.d. 0.16) and 1.7 mm (s.d. 0.41), respectively. Cut-off values are 0.42, 0.34, 0.29, 0.37 and 1.0 mm, respectively, with 100% sensitivities and specificities for common superficial temporal arteries, for frontal branches and for axillary arteries and sensitivities of 97.2 and 87.5% and specificities of 98.7 and 98.8% for parietal branches and facial arteries, respectively. The intraclass correlation coefficient was between 0.87 and 0.98. Conclusion IMT measurement can correctly distinguish vasculitic from normal arteries in suspected GCA.

Background To evaluate the utility of the recently introduced SOLAR score (sonography of large joints in Rheumatology), which has been validated in RA patients, in a cohort of patients with Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) presenting with involvement of large peripheral joints. Methods The recently established SOLAR score has been designed to determine the degree of inflammation in the shoulder, the elbow, the hip and the knee joint in patients suffering from RA. Since large joints are frequently involved in PsA and AS, synovitis and synovial vascularity were scored semiquantitatively (grade 0–3) by grey scale (GSUS) and power Doppler ultrasound (PDUS) utilizing the validated scoring system. Each joint was scanned from different angles, the knee joint for example was divided into four areas to score for synovitis: the suprapatellar longitudinal, the medial longitudinal, the lateral longitudinal, and the posterior region. Each area was scored from 0–3, so a maximum score of 12 could be achieved. PsA and AS patients presenting with peripheral joint disease involving large joints were examined at baseline, 3 and 6 months after initiation of local or systemic therapy (DMARDs/Biologics). For evaluation of the inflammatory status, the erythrocyte sedimentation rate (ESR) was determined. Results A cohort of 126 patients were enclosed, and 83 of these were followed for 6 months. At baseline before modification of the therapy, patients received DMARDs (n = 83), DMARDs plus biologics (n = 30), or biologic monotherapy (n = 29). Following intervention, all US scores demonstrated a marked improvement. The GSUS and the PDUS scores for all joint areas, except the PDUS score of the hip, exhibited a significant improvement (p Conclusion The SOLAR score, which has been recently introduced for RA patients, is a very suitable instrument for the qualitative and quantitative evaluation of large joint involvement in PsA and AS patients and allows for treatment monitoring.

Background Ultrasound (US) is increasingly used in the diagnosis of giant cell arteritis (GCA). US findings mainly rely on morphology (“halo-sign” and “compression sign”). Increasing resolution of modern US probes allows exact intima-media thickness (IMT) measurement of normal and vasculitic temporal arteries. No data have yet been published on IMT of temporal, facial and axillary arteries in GCA patients compared to healthy controls. Objectives To evaluate the mean IMT thickness of arteries commonly involved in GCA in GCA patients and controls, and to determine if cut-off values can define pathology. Methods Fourty newly diagnosed GCA patients of a fast-track GCA clinic and 40 age- and sex-matched controls were included between October 2014 and December 2015. The diagnosis of GCA was established by two very experienced rheumatologists (WAS or AJ) on the basis of clinical presentation, laboratory tests and US results. The diagnosis was confirmed after 6 months in patients who were included until July 2015. IMT measurement was performed at or within 24 hours after the first visit. The common superficial temporal arteries with their frontal and parietal branches and the facial arteries were bilaterally examined with a 10–22 MHz probe (Esaote MyLab Twice). A 6–18 MHz probe was used for both axillary arteries. In total, IMT measurement was performed at 800 sites. The mean IMT values of the different arteries were compared between controls and patients with active vasculitis of the corresponding artery by means of a Mann-Whitney test. ROC analysis was performed to determine the best cut-off value, balancing sensitivity and specificity, to discriminate between a normal and a vasculitic artery. Results Both groups of 40 participants, each, included 27 females. The mean age was 72 years (SD 9). Of the 40 GCA patients, 22 (55%) had indurated temporal arteries on clinical examination, 16 (40%) had symptoms of polymyalgia rheumatica. The mean duration of symptoms was 15 weeks (SD 19). Five patients (13%) had visual impairment (anterior ischaemic optic neuropathy, 3; amaurosis fugax, 1; diplopia, 1). Twenty-eight patients (70%) described headache; and 17 (43%) had jaw claudication. The mean ESR was 82 mm/h (SD ± 28); and the mean CRP was 107 mg/dL (SD 79). In 26 patients (65%) the axillary arteries were involved of whom 9 had no involvement of temporal arteries. Table 1 shows IMT of affected arteries in GCA patients compared to controls and cut-off values for distinguishing normal from inflamed arteries. Maximum IMT of controls and minimum IMT of vasculitic segments in GCA was 0.34 mm/0.42 mm for the common superficial temporal arteries, 0.32 mm/0.34 mm for the frontal branch, 0.31 mm/0.24 mm for the parietal branch, 0.42 mm/0.31 mm for the facial artery and 0.86 mm/1.0 mm in the axillary arteries, i.e. no overlap occurred in the common superficial temporal arteries, the frontal branch and the facial arteries. Conclusions IMT measurement of temporal, facial and axillary arteries can correctly distinguish vasculitic from normal arteries in suspected GCA in addition to morphological parameters. Data for wall diameters are needed for future longitudinal trials to monitor GCA treatment. Disclosure of Interest None declared

Glucocorticoids are the mainstay of therapy for giant cell arteritis (GCA) and Takayasu's arteritis. However, a significant proportion of patients have a glucocorticoid-dependent or resistant disease course and serious adverse events are frequent. This article summarizes the current evidence on the use of biologic treatments in large-vessel vasculitis (LVV).Antitumour necrosis factor (TNF) treatment strategies have failed to show efficacy in GCA, whereas their role in Takayasu's arteritis is yet unclear. Preliminary reports on the use of the anti-interleukin-6 receptor antibody tocilizumab (TOC) in both GCA and Takayasu's arteritis emerge. TOC was both able to spare glucocorticoid doses but could also induce remission in untreated GCA patients when used as monotherapy. There is little evidence for the use of biologic drugs in LVV associated with systemic rheumatic diseases. Case series suggest efficacy for anti-TNF antibodies in aortitis associated with relapsing polychondritis and pulmonary artery aneurysm associated with Behcet's disease.TNF inhibition does not seem to save glucocorticoids or prevent relapses in GCA. Blocking TNF may provide benefit to difficult-to-treat patients with Takayasu's arteritis, relapsing polychondritis and Behcet's disease-associated LVV. Emerging reports on the use of TOC suggest an important role of IL-6 in the pathogenesis of large-vessel vasculitides and deserve further investigation. The use of TOC monotherapy to induce remission in untreated GCA patients proves fascinating.

Giant cell arteritis (GCA) is a form of large vessel vasculitis that preferentially involves branches of the external carotid artery. It is the most common vasculitis in individuals over the age of 50 years (1). The estimated annual incidence of GCA in population-based studies of Olmsted County, MN is 18.8 cases per 100,000 persons 50 years of age or older (1). Mean age at diagnosis of GCA in this cohort was 74.8 years (2). Since GCA is almost never seen in individuals below the age of 50 years, immunosenescence may play a role in disease pathogenesis (3). Immunosenescence may also increase the risk of cancer, which like GCA occurs predominantly, although not exclusively, in the elderly (4-6). Based on the Surveillance, Epidemiology, and End Results (SEER) Program data, the median age at diagnosis of cancer was 67 years for the years 1999-2003 (7). It is estimated that starting at 65 years of age, approximately 43% of men and 30% of women will develop cancer (7). Previous studies have suggested an association between cancer and GCA. In a retrospective series, 7.4% of 271 consecutive patients with GCA also had a concurrent malignancy within the first year of GCA diagnosis (8). Other studies suggest that the risk of cancer in patients with GCA is similar to that of the general population (9). Patients with other vasculitides, such as ANCA-associated vasculitis (specifically Wegener’s Granulomatosis) have been found to have an increased risk of malignancy (10) (11-13). Studies assessing the prevalence of malignancy in GCA are limited. In this population-based case-control study, we investigated risk of cancer preceding the diagnosis of GCA. The study of such associations could further our understanding of GCA and common environmental or genetic factors that may predispose the same individual to two different diseases.

Giant cell arteritis (GCA) is the most common vasculitis in people over the age of 50 years, with a peak incidence in the 70–80 year age group [1]. Given the age restriction of this disease, immunosenescence may play a role in disease pathogenesis [2]. Immunosenescence has also been proposed as a possible mechanism by which the elderly are predisposed infections and malignancy [3, 4]. At present, there is conflicting information about malignancy risk in GCA patients. Case reports of concurrent GCA and malignancy [5–9] suggest it may be a paraneoplastic phenomenon in some cases. In a retrospective case series of 271 patients with GCA, concurrent malignancy was noted in 7.4% of GCA patients [10]. In a case-control study by Haga, et al. no overall increase in malignancy was found in patients with GCA and polymyalgia rheumatica (PMR). However, the investigators did find an increased risk of malignancy in the subset of GCA patients with a positive temporal artery biopsy (OR: 2.35; 95% CI 1.03, 5.34) [11]. A subsequent population-based study of malignancy in GCA and PMR patients found no such increased risk of cancer in GCA patients. However, only 80 of the 398 patients in this study had GCA [12]. Finally, in a population-based study from Spain, the authors evaluated mortality in GCA patients with cancer and found no increased mortality [9]. The somewhat contradictory findings of these few studies make it difficult to draw any definitive conclusions regarding risk of malignancy in patients with GCA. Clarifying the risk of cancer in GCA has prognostic implications for GCA patients. Knowledge of an increased risk of cancer could alter cancer screening practices in these patients. To address this issue, we employed a population-based incident cohort of GCA patients, to calculate and compare the incidence of malignancy in GCA patients to that of age- and gender-matched cohort of non-GCA patients from the same geographic region.

Giant cell arteritis (GCA) is a granulomatous vasculitis of large and medium-sized arteries that occurs in individuals aged ≥50 years.1 A recent study suggested that the age at incidence of GCA may be increasing.2 To address this issue, we studied the trends in mean age at onset of GCA over a 55-year period. A population-based incident cohort of 173 patients with GCA diagnosed between 1 January 1950 and 31 December 1999 has been established using the resources of the Rochester Epidemiology Project.3 4 We extended the cohort to include 34 new cases of GCA diagnosed between 1 January 2000 and 31 December 2004. Patients were included in the study if they fulfilled the 1990 American College of Rheumatology criteria.5 Age- and sex-specific incidence rates were calculated based …