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ZUSAMMENFASSUNGDie Sarkoidose ist in Nordeuropa die häufigste granulomatöse Erkrankung. Sie kann prinzipiell nahezu alle Organe betreffen. Die Lunge ist jedoch mit 90–95 % das am häufigsten betroffene Organ. Die pulmonale Sarkoidose kann von einem asymptomatischen Befall bis hin zu einer interstitiellen Fibrose mit schwer eingeschränkter Lungenfunktion auftreten. Mit dem konventionellen Röntgen wird die pulmonale Sarkoidose in 4 Typen unterteilt. Neben der Lungenfunktion ist der radiologische Befallstyp mit entscheidend für die Therapieindikation. Wichtige Bausteine in der Diagnostik sind neben der radiologischen Bildgebung die Bestimmung der Lungenfunktion sowie die Bronchoskopie zur histologischen Diagnosesicherung. Daneben muss bei möglichem Multiorganbefall eine umfangreiche Organdiagnostik zur Erfassung weiterer Organmanifestationen erfolgen. Die Therapie besteht an erster Stelle aus der Gabe von Glukokortikoiden sowie bei unzureichender Wirkung oder Steroid-induzierten Nebenwirkungen aus der zusätzlichen Gabe von Immunsuppressiva. Hier steht an vorderster Stelle eine Therapie mit Methotrexat (MTX).

C-Reactive protein and erythrocyte sedimentation rate are crucial parameters used to monitor giant cell arteritis (GCA). Given that tocilizumab is approved for the treatment of GCA, these parameters are less sensitive because of the effects of interleukin-6 receptor blockade. Thus, the optimal method for monitoring GCA patients undergoing tocilizumab therapy, especially patients exhibiting a persistent thickened vessel wall in large vessels, remains unclear. Contrast-enhanced ultrasonography (CEUS) can increase the visibility of tissue perfusion by slow blood flow, which cannot be detected by power color doppler. We used CEUS to investigate patients with active and inactive GCA of the large vessels (active large vessel arteritis [aLVV]/inactive large vessel arteritis [iLVV]) who were not administered tocilizumab in this proof-of-concept study. After injection of the ultrasound contrast agent, the contrasted area (CA) of large vessels in a transverse section was calculated twice: first when the lumen was contrasted completely and once again 4–8 s later. We investigated the value of increase in CA that exhibited the best sensitivity and specificity for aLVV. Twenty-four patients were included in this study: 15 with aLVV and 9 with iLVV. The CA increased from 32.2 ± 16.8 to 52.5 ± 21.3 mm2 (p

Eine solide rheumatologische Grundausbildung im Medizinstudium ist aus 2 Grunden fur die Versorgung rheumatischer Patientinnen und Patienten in der Zukunft essenziell: Einerseits werden zukunftige Hausarztinnen und Hausarzte die Muster entzundlich rheumatischer Erkrankungen beherrschen mussen, um sie rasch genug zu erkennen und die Neuerkrankten rechtzeitig und gezielt in die rheumatologische Versorgung weiterzuleiten. Anderseits ist der weiter bestehende Mangel an Rheumatologinnen und Rheumatologen nur dann perspektivisch zu beheben, wenn es uns gelingt, Interesse fur unser Fach zu wecken. Adaquate rheumatologische Strukturen sind nur in einem Teil der medizinischen Fakultaten Deutschlands vorhanden. Strukturelle Verbesserungen gehen insgesamt nur in kleinen Schritten voran, wurden aber an einigen Standorten erreicht. Je besser die lokalen Strukturen, desto eher ist es auch engagierten rheumatologischen Lehrenden moglich, alle Studierenden der Humanmedizin zu erreichen. Die prufungsrelevanten Lernziele werden vermutlich ab 2026 durch den Nationalen Kompetenz-basierten Lernzielkatalog Medizin (NKLM) vorgegeben werden, der aktuell gemeinsam mit dem Institut fur Medizinische und Pharmazeutische Prufungsfragen (IMPP) in eine Endfassung gebracht wird. Wenn es, wie es derzeit aussieht, gelingt, die systemischen Autoimmunerkrankungen und entzundlich rheumatischen Erkrankungen dort adaquat abzubilden, werden Studierende in Zukunft deutschlandweit besser uber diese Erkrankungen Bescheid wissen und sie schneller erkennen. Daher ist die Arbeit am NKLM von groser Bedeutung. Neben der Arbeit an den Lernzielen bedarf es aber auch deutschlandweit zuganglicher Lernunterlagen auf aktuellem Stand. Diese Lucke sollte das Skriptum schliesen, das die Kommission Studentische Ausbildung der Deutschen Gesellschaft fur Rheumatologie (DGRh) gerade fertiggestellt hat und das nun auf der DGRh-Homepage verfugbar ist.

To study the impact of glucocorticoid maintenance dose and treatment duration on outcomes in patients with AAV (ANCA-associated vasculitis) with emphasis on infectious complications. A total of 130 AAV patients from two German vasculitis centers diagnosed between August 2004 and January 2019 treated with cyclophosphamide and glucocorticoids for induction therapy and glucocorticoids for maintenance therapy were retrospectively enrolled. We investigated the influence of glucocorticoid maintenance therapy on patient survival, time to relapse, kidney function, infectious complications and irreversible physical damage. The patients were divided into the following groups: patients treated according to the predefined reduction scheme ($$\ge $$ ≥ 7.5 mg had an increased rate of infectious episodes per patient (1.7 vs. 0.6; p p = 0.007), pneumonia (p = 0.003), opportunistic pneumonia (p = 0.022) and sepsis (p = 0.008). Especially pneumonia during the first 24 months after disease onset [hazard ratio, 3.0 (95% CI 1.5 − 6.1)] led to more deaths from infection (p = 0.034). Glucocorticoid maintenance therapy after 6 months had no impact on relapse rate or patient survival and decline in kidney function was comparable. Glucocorticoid maintenance therapy with $$\ge $$ ≥ 7.5 mg after 6 months is associated with more severe infectious complications leading to an increased frequency of deaths from infection. Glucocorticoid maintenance therapy has no effect on time to relapse or patient survival and should therefore be critically revised throughout the aftercare of AAV patients.

Although the lungs remain the main target of SARS-CoV-2, other organs, such as kidneys, can be affected, which has a negative impact on the outcomes of COVID-19 patients. Although previous studies of kidney disease in COVID-19 reported mainly SARS-CoV-2-induced tubular and interstitial injury, there is growing evidence coming out of Africa of glomerular involvement, especially collapsing glomerulopathy seen particularly in people of African descent. We report a case of collapsing glomerulopathy revealed by acute kidney injury and a new onset of full blown nephrotic syndrome in a black Congolese patient coinfected with COVID-19 and malaria.

Objectives To test the ability of an established traditional cardiovascular (CV) risk prediction score [Systematic COronary Risk Evaluation (SCORE)] and its EULAR modified version (mSCORE) to identify antisynthetase syndrome (ASyS) patients at high CV risk and to examine for the first time associations of CV and cerebrovascular surrogate markers with clinical and immunological ASyS parameters. Methods SCORE/mSCORE and the gold standard marker of aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] were examined in ASyS patients and healthy controls. Moreover, sonography of the common- (CCA) and internal- (ICA) carotid arteries was performed in subsets of both groups, evaluating carotid intima-media thickness (cIMT), plaques and Doppler sonographic cerebrovascular surrogates [resistance (RI) and pulsatility (PI) indices]. Results We recruited 66 ASyS patients and 88 controls. According to mSCORE, 10% of the patients had high CV risk. However, cfPWV and carotid sonography revealed an increased CV risk in 21.2% and subclinical carotid atherosclerosis (SCA) in 85.7% of the patients, respectively. cfPWV and cIMT were higher in patients compared with controls (Padj=0.021 and Padj=0.003, respectively). In the ASyS group, cfPWV and cIMT correlated significantly with age (r = 0.679; P Conclusion ASyS patients had higher aortic stiffness and SCA compared with controls, even after adjustment for confounders. SCORE/mSCORE performed poorly in identifying high-risk patients compared with cfPWV and carotid sonography. Thus, cfPWV and carotid sonography may improve CV and cerebrovascular screening in ASyS.

Background and Aims: Liver involvement in sarcoidosis may occur in up to 60% of all patients. As many patients experience only minor symptoms, a high number of undiagnosed cases must be assumed. In order to successfully identify patients with hepatic sarcoidosis, a throughout characterization of these patients and their course of disease is necessary. Methods: We collected 40 patients from four German centers to evaluate current treatment standards and course of disease. All of our patients underwent liver biopsy with histologically proven granulomatous hepatitis. Results: Detailed characterization of our patients showed an overall benign course of disease. Treatment was very diverse with glucocorticoids for 1 year in 55% (22/40), 5-10 years in 18% (7/40), and permanently in 18% (7/40). Other treatments included disease-modifying anti-rheumatic drugs (DMARDs), the conventional non-biological type in 53% of all patients (of these 81% received azathioprine, 46% metotrexate, 10% hydroxychloroquine, 10% mycophenolate mofetil and 10% cyclophosphamide and biologicals in 8%. Despite these very diverse treatments, patients generally showed slow progression of the disease. Two patients died. None of our patients received a liver transplantation. Conclusions: Patients received diverse treatments and generally showed slow progression of the disease. Based on our experience, we proposed a diagnostic work up and surveillance strategy as a basis for future, prospective register studies.

Background Cytotoxic Natural Killer (NK) cells are increasingly recognized as a powerful tool to induce targeted cell death in cancer and autoimmune diseases. Still, basic blood NK cell parameters are poorly defined. The aims of this study were 1) to establish reference values of NK cell counts and percentages in healthy adults; 2) to describe these parameters in the prototype autoimmune disease group ANCA-associated vasculitis (AAV); and 3) to investigate whether NK cell counts and percentages may be used as activity biomarkers in the care of AAV patients, as suggested by a preceding study. Methods CD3-(CD56 or 16)+ NK cell counts and percentages were determined in 120 healthy adults. Lymphocyte subset and clinical data from two German vasculitis centers were analyzed retrospectively (in total 407 measurements, including 201/49/157 measurements from 64/16/39 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), respectively). Results CD3-(CD56 or 16)+ NK cell counts and percentages in healthy adults were highly variable, not Gaussian distributed and independent of age and sex. NK cell percentages ranged from 1.9 to 37.9% of lymphocytes, and were significantly more dispersed in AAV (0.3 to 57.6%), while the median percentage was not different between AAV and healthy donors. In contrast, median NK cell counts were significantly lower in AAV compared to healthy donors. Sub-group analyses revealed that NK cell counts were low independent of AAV entity and disease activity. Azathioprine therapy was associated with significantly lower NK cell counts and percentages compared to non-azathioprine therapies. In 13.6% of azathioprine-treated patients, percentages were Conclusions NK cell counts and percentages in blood are heterogeneous and can presently not be recommended as biomarker in clinical care of AAV patients. Azathioprine treatment was associated with significantly low NK cells. These findings may be relevant for the development of drugs that aim at exploiting NK cell cytotoxicity and may help to identify patients at risk to develop malignant or infectious co-morbidities.

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 Cast nephropathy (CN) is associated with a unfavourable outcome in monoclonal light chain (mLC) disease, but also more possible LC-related renal diseases as well as non-LC-related disease can occur. Thus, it is crucial to understand the underlying renal disease. On the other hand, LC can interfere with coagulation preventing kidney biopsy as the gold standard. We sought to develop a non-invasive algorithm to diagnose CN with a good sensitivity and specificity. Method We analysed data from patients with mLC disease who underwent kidney biopsy. The patients were classified in 4 groups according the renal histology: CN, AL amyloidosis, light chain deposition disease, and other renal disease. Afterwards, different algorithms were calculated for their sensitivity and specificity. Results CN showed a significant higher concentration of serum-free LC and urine LC (LCu), but there was a wide and overlapping range with the other groups. The best accuracy was achieved for a LCu/GFR ratio >2 in patients with lambda LC and either a LCu/GFR > 1 and proteinuria 5 in patients with proteinuria >8 g/24 h in patients with kappa LC. In lambda LC, the sensitivity and specificity for CN was 94% and 90%, respectively; in kappa LC 87% and 81%, respectively. Discussion In patients with coagulation disturbances due to LC, a non-invasive algorithm can separate patients with CN from other renal disease in mLC disease.

Treatment of ANCA-associated vasculitis (AAV) improved over the last decades but disease-unspecific agents such as cyclophosphamide are still associated with serious adverse events, including high rates of infectious complications and malignancy with increased mortality. In this comparative cohort study, we included 121 AAV patients with renal involvement from 2 German vasculitis centers. Patients were separated into subsequent groups: 2.5 to 3 g vs >3 g cumulative cyclophosphamide induction dose. We investigated if a cyclophosphamide induction dose of 2.5 to 3 g could maintain efficacy while minimizing adverse events in AAV patients with renal involvement. Patients with 2.5 to 3 g vs >3 g cumulative cyclophosphamide (median 3.0 g vs 5.5 g, P

BackgroundCytotoxic Natural Killer (NK) cells are an important target of new drugs entering the clinics, including checkpoint inhibitors and cell-depleting therapeutic antibodies. Still, basic blood NK cell parameters are poorly defined in healthy adults and in chronic inflammatory diseases like ANCA-associated vasculitis (AAV) which may alter the distribution of lymphocytes. The aims of this study were 1) to establish reference values of NK cell counts and percentages in healthy adults; 2) to describe these parameters in AAV; and 3) to investigate whether NK cell counts and percentages may be used as activity biomarker in the care of AAV patients, as suggested by a preceding study.MethodsCD3-(CD56 or 16)+ NK cell counts and percentages were determined in 120 healthy adults. Lymphocyte subset data from two German vasculitis centers were retrospectively analyzed (in total 407 measurements, including 201/49/157 measurements from 64/16/39 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), respectively).ResultsCD3-(CD56 or 16)+ NK cell counts and percentages in healthy adults were highly variable, not Gaussian distributed and independent of age and sex. NK cell percentages ranged from 1.9 to 37.9% of lymphocytes, and were significantly more dispersed in AAV (0.3 to 57.6%). We further found that NK cell counts and percentages were different between AAV entities. However, during active disease, NK cell counts were consistently low in each AAV entity compared to healthy donors. NK cells were especially low in inactive EGPA. In 18% of EGPA patients we observed percentages of 1% or below which may be interpreted as temporary NK cell deficiency. Findings on differences between active and inactive GPA were discrepant between vasculitis centers.ConclusionsNK cell counts and percentages in blood are highly variable. This variability is further enhanced in systemic inflammatory diseases, and includes patients with temporary NK cell deficiency, in particular in EGPA. NK cell counts and percentages can presently not be recommended as biomarker in clinical care of AAV patients.

Resume Objectifs L’atteinte de la hanche est courante dans les affections rhumatologiques mais son diagnostic peut s’averer difficile en particulier en l’absence d’examen IRM. L’echographie en mode B permet de detecter une dilatation capsulaire mais la differenciation entre un epanchement articulaire et une proliferation synoviale reste difficile puisque ces deux entites apparaissent hypoechogenes. L’echographie en mode Doppler puissance (DP) ne parvient pas toujours a detecter la vascularisation de la hanche. Nous avons donc evalue l’interet de l’echographie de contraste (EC) dans l’exploration de la hanche. Methodes Trente-six hanches de patients atteints d’une maladie rhumatismale connue et presentant des douleurs de la hanche ainsi que 5 hanches de temoins sains ont ete analysees au moyen de l’echographie en mode B, du DP et de l’EC. Nous avons procede a une etude semi-quantitative du rehaussement a l’echographie de contraste pour detecter le degre d’hypervascularisation par comparaison au tissu periarticulaire. En mode B, nous avons mesure la distance separant le col femoral de la capsule articulaire (DNC), puis compare les resultats avec la marge avasculaire intra-articulaire (AIM) visible a l’EC a l’aide de tests t et de tableaux croises. Resultats Les signaux Doppler ont ete recus dans seulement 2/36 cas (5,6 %). L’echographie en mode B permettait d’etablir le diagnostic de coxite dans 64 % des hanches symptomatiques. Dans 4 cas (11 %), le diagnostic a ete corrige apres le recours a l’EC. Parmi les patients atteints d’une coxite definie, 14 hanches (73,7 %) ont montre une hypervascularisation°2 a l’EC, cinq°1 (26,3 %) et aucune°0 (χ 2 = 3,277, p p p Conclusions Dans la majorite des cas, les parametres cliniques combines a l’echographie en mode B ont ete suffisants pour evoquer le diagnostic de coxite. Cependant, l’echographie de contraste reste une technique tres utile pour visualiser et quantifier le degre d’hypervascularisation mais egalement differencier un epanchement d’une proliferation synoviale.

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage, however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p &lt, 0.001–p &lt, 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031, Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.

Large-vessel vasculitis (LVV) is a group of diseases mainly comprised of giant-cell arteritis (GCA), Takayasu arteritis, and a series of rare diseases like Behçet's disease, IgG4-related disease, infectious aortitis, and other unfrequent entities. Besides clinical and laboratory features, Doppler sonography (DS) can assist in establishing the diagnosis. Its diagnostic sensitivity has been evaluated in various studies, most of them, however, in temporal arteritis (TA) respectively in LVV with involvement of the temporal artery. Little is known in extracranial LVV. We retrospectively evaluated the diagnostic accuracy of DS in 30 patients with extracranial, non-temporal LVV using the highly sensitive PET/CT as method of reference in comparison to 20 controls who were found to have no LVV. We investigated ten arterial sites and documented the presence of the sonographic halo sign. Sensitivities of DS for LVV were highest in the subclavian and axillary arteries (71.4%/72.2%) and low in the abdominal aorta (26.1%) and the common femoral artery (16.7%). DS detected 24 out of 30 cases of LVV (overall sensitivity 80.0%). The LVV cases where DS was completely negative did not significantly differ in leukocyte count, C-reactive protein, or erythrocyte sedimentation rate from LVV cases with positive DS. DS is a potent method in diagnosing extracranial LVV especially in the axillary and the subclavian arteries. Aortic, intraabdominal, and lower extremity artery manifestations, however, are often missed by DS. A second imaging modality (e.g., PET/CT) is therefore required.

Objectives Hip involvement is common in rheumatological diseases but can be difficult to diagnose, especially in absence of MRI. B-mode ultrasound (US) detects joint capsule distention while distinguishing effusion from proliferative synovial tissue is strenuous since both appear hypoechoic. Power Doppler ultrasound (PDUS) often fails to detect vascularisation in the hip. We therefore evaluated contrast-enhanced ultrasound (CEUS) in the hip joint. Methods We investigated 36 hip joints of patients with known rheumatological joint diseases presenting with hip pain and 5 hips of healthy controls using B-mode US, PDUS and CEUS. We assessed CEUS hypervascularisation semiquantitatively comparing to the periarticular tissue. In B-mode, we measured the distance between femoral neck and joint capsule (DNC) and compared the results to the avascular intraarticular margin (AIM) in CEUS using t-tests and crosstables. Results PDUS signals were received in only 2/36 cases (5.6%). B-mode US established the diagnosis of coxitis in 64% of all symptomatic hip joints. In 4 cases (11%), the diagnosis was revised after the use of CEUS. In patients with definite coxitis, 14 hips (73.7%) showed CEUS hypervascularisation°2, five°1 (26.3%) and none°0 (χ2 = 3.277, P Conclusions In most cases, clinical parameters together with B-mode US findings are sufficient to diagnose coxitis. However, CEUS is capable of visualizing and quantifying the degree of hypervascularisation and enables the discrimination between effusion and proliferative synovial tissue.

Power Doppler ultrasound is used to assess joint vascularity in acute arthritis. PDUS signals have been correlated with synovial histology and bone deterioration. Little is known about the correlation between power Doppler signals and synovial white blood count. In our study, we analyzed power Doppler signals in inflammatory joint diseases including gout, calcium pyrophosphate deposition disease, rheumatoid arthritis, spondyloarthritis and others and correlated power Doppler signals with synovial white blood count and with serologic markers of inflammation.We retrospectively evaluated 194 patients with arthritis. All patients underwent joint sonography, power Doppler ultrasound, synovial fluid analysis and blood examination of C-reactive protein and erythrocyte sedimentation rate. Correlation analyses (Spearman and Pearson), Chi(2) test, t-tests, a unifactorial ANOVA and regression analyses were applied.Hypervascularisation in power Doppler was most prominent in gout and calcium pyrophosphate deposition disease. Spondyloarthritis and non-inflammatory joint diseases presented with low degrees of hypervascularisation. Mean synovial white blood count did not differ significantly between crystal-related arthritides, rheumatoid arthritis, spondyloarthritis or other inflammatory joint diseases. There was a positive but weak correlation between power Doppler signals and synovial white blood count (P0.001, rs=0.283), erythrocyte sedimentation rate (P0.001, rs=0.387) and C-reactive protein (P0.001, rs=0.373) over all diagnoses. This was especially relevant in rheumatoid arthritis (P0.01, rs=0.479). Power Doppler degrees 0 and 1 were able to predict synovial leukocytes5/nL, degrees 2 and 3 predict leukocytes≥5/nL (P0.001).

Background C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are important parameters in the monitoring of LVV. Since Tocilizumab is approved for treatment of LVV these cheap and easy repeatable parameters are worthless because of their normalisation by Tocilizumab. MRI and PET-CT as an alternative are not only much more expensive, they are also not arbitrarily repeatable and available. Thus, monitoring of LVV-Patients undergoing a Tocilizumab therapy remains unclear – especially upon showing a persisting thickened vessel wall. Objectives CEUS can increase the visibility of tissue perfusion, particularly if there is a very slow bloodflow, which cannot be detected by (power)-doppler sonography. Methods In this proof of concept study we investigated patients with active and inactive LVV (aLVV/iLVV) with CEUS. After injection of ultrasound contrast agent we measured the contrasted area of large vessels in a transverse section first if the lumen was completely contrasted and once again 4-8 seconds later. If the vessel wall incorporated the contrast agent the contrasted area increased (Fig 1). The increase of the contrasted area (CA) was correlated with CRP and ESR. Patients were only included if they were not treated with Tocilizumab and therefore ESR and CRP were usable to evaluate the disease activity. Results Investigated were 16 patients (13 female, 3 male), 8 with aLVV and 8 with iLVV, respectively. The mean CRP was 85±69 (aLVV) vs. 4±2 mg/l (iLVV) (p Conclusion The results of our proof of concept study demonstrate, that CEUS can detect aLVV with a good sensitivity and specificity. Including CEUS in clinical routine will be much easier repeatable, save, quicker and by far more cost-effective then MRI or PET-CT. CEUS might be a good method for monitoring disease activity in LVV treated with Tocilizumab. The limitation of our study is the small number of patients, the missing blinding of the investigator and the method intrinsic fact, that you can’t investigate all involved vessels by ultrasound/CEUS. References None Disclosure of Interests Raoul Bergner Speakers bureau: Abbvie, Roche, Novartis, Bristol Myers Squibb, Jan Splitthoff: None declared, Daniel Wadsack Speakers bureau: Bristol Myers Squibb

The German Society of Rheumatology and the Committee for Student Training investigated what effects the structures in university medicine have on student teaching. In February 2014 a questionnaire was sent to the teaching staff and Deans of each of the 37 medical faculties. Of the locations seven were classified as being independent rheumatological university hospitals and nine universities had a W2/W3/C3 grade professor as head of a department of clinical rheumatology but answerable to superiors. In the 37 faculties in Germany the proportion of lecture hours, the proportion of obligatory lecture hours, the number of hours for practical exercises and the number of hours for bedside teaching were distributed very differently and as a rule higher in universities with academic freedom. Not all medical faculties have obligatory teaching in the field of clinical rheumatology. On average medical students see five patients with rheumatological symptoms during their studies. In summary, over the past years it has not been possible to successfully utilize the great importance of rheumatology for society and the innovation potential of this discipline in order to improve the integration of clinical rheumatology into universities.

Background:Antisynthetase Syndrom (ASyS) is an autoimmune overlap disease characterized by antiaminoacyl-tRNA-synthetase (anti-ARS) antibodies and the classic triad of arthritis, myositis and interstitial lung disease (ILD) (1). Markers of cardiovascular (CV) or cerebrovascular (CVB) risk have never been examined in ASyS.Objectives:Aim of this study (RIsk of CARdiovascular Disease in ASyS: RI.CAR.D.A.) was to test the ability of an established traditional CV risk prediction score (Systematic Coronary Risk Evaluation-SCORE) and its EULAR modified version (mSCORE) to identify ASyS patients at high CV risk. Moreover, we sought to examine for the first time associations of CV surrogate markers with clinical and immunological ASyS parameters.Methods:SCORE/mSCORE and the gold standard marker of aortic stiffness (carotid-femoral pulse wave velocity-cfPWV) were examined in patients with ASyS and healthy controls in a multicenter setting (6 Rheumatology Centers). Moreover, sonography of the common- (CCA), internal- (ICA) and external- (ECA) carotid arteries was performed in subsets of both groups, evaluating carotid intima-media-thickness (cIMT), plaques and duplex-sonographic indices of CBV risk such as the resistance- (RI) and pulsatility-index (PI).Figure 1.Carotid Doppler surrogate markers of cardiovascular and cerebrovascular risk in controls and ASyS (case).cIMTCarotid intima media thickness;CAA(common-),ICA(internal),ECA(external) carotid artery;RIresistance index;PIpulsatility index. (all;p< 0.05)Results:We recruited 66 ASyS patients with different anti-ARS and 88 controls. According to mSCORE5/50 (10%) of the patients had high CV risk. However, cfPWV and carotid sonography (CS) revealed an increased CV risk in21.2%and subclinical carotid arteriosclerosis (plaques and/or cIMT>0.9 mm) (SCA) in85.7%of the patients respectively. ROC analyses showed similarly poor diagnostic performances of SCORE/mSCORE in comparison to cfPWV(>10 m/s) and SAC by areas under the curve (AUC) of0.56 (95%CI=0.39-0.73) and0.63 (95%CI=0.3-0.96),respectively. cfPWV and SCA were higher in ASyS patients compared to controls (padj=0.021andp=0.003, respectively). cfPWV and cIMT correlated in the patient group significantly with age (r=0.679; prespectively).Moreover, cfPWV correlated with BMI (padj=0.001) and diabetes(padj=0.043). ACC-RI and ACC-PI showed significant associations with a marker of myositis activity [creatine phosphokinase (CPK):r=0.629;p=0.012andr=0.574;p=0.032, respectively]. Finally, ACI-RI and ACI-PI values were higher in patients with ILD (both;p=0.039).Conclusion:This is the first report of higher aortic stiffness and SCA in ASyS patients compared to controls. Active myositis and presence of ILD were associated with higher CVB risk parameters. Furthermore, SCORE/mSCORE performed poorly in identifying patients at high CV risk and carotid arteriosclerosis compared to cfPWV and CS respectively. Thus, cfPWV and CS could improve CV and CBV screening in ASyS patients.References:[1]Cavagna L, et al. Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome.Medicine2015;94:1144.Disclosure of Interests:None declared

The purpose of this article is to provide understanding of renal sarcoidosis, the different types of renal sarcoidosis, disease burden of renal involvement, and treatment options.The frequency of renal involvement seems to be underestimated, but renal sarcoidosis represents a relevant group of organ manifestations and significantly adds to the patient's morbidity. Because histopathological analysis of renal biopsy specimens can reveal various entities, a diagnostic workup is necessary in every patient with sarcoidosis.If systematically screened for renal manifestations are likely to occur in up to 25-30% of all sarcoidosis patients. The most common histological form of renal sarcoidosis is the granulomatous interstitial nephritis; however, granulomas can be absent. Furthermore, one can find various forms of secondary glomerulonephritis. In cases with dysregulated calcium homeostasis, nephrocalcinosis and nephrolithiasis are commonly detectable kidney diseases. AA amyloidosis or renal masses because of granuloma formation are considered to be rare manifestations. In addition to glucocorticoids various immunosuppressive treatments such as tumor necrosis factor alpha inhibitors have proven to be effective based on case series.

Background Antisynthetase syndrome (ASSD) is an autoimmune disease characterised by the clinical triad arthritis, myositis, and interstitial lung disease (ILD). Despite Raynaud’s phenomenon (RP) is another typical feature of ASSD, nailfold videocapillaroscopy (NVC) assessment of these patients has been only sporadically described, without the elucidating data for clinicians. Objectives To describe NVC features of ASSD patients and to investigate possible correlations with clinical and serological features of the disease. Methods We retrospectively analysed NVC images of 190 ASSD patients (females/males 3.76, mean age 49.7±12.8 years, mean disease duration 51.2±71.4 months, 133 anti-Jo-1 and 57 non-anti-Jo-1 positive patients). For each patient, we examined number of capillaries, giant capillaries, micro-haemorrhages, avascular areas, ramified capillaries, and the presence of scleroderma (SSc) patterns. Finally, we correlated NVC features with clinical and serological findings of ASSD patients. Results NVC abnormalities were observed in 62.1% of AASD patients compared with 29.3% of a group of 75 patients with primary Raynaud’s phenomenon (p Conclusions NVC abnormalities are commonly observed in ASSD, independently to the occurrence of RP. The presence of a SSc-like pattern should let to identify a more defined ASSD subtype and prospective studies could confirm the association with clinical and serological features of ASSD. Disclosure of Interest None declared

In distinguishing urate arthritis (UA) from non-crystal-related arthritides, joint sonography including the detection of the double contour sign (DCS) and hypervascularization using power Doppler ultrasound (PDUS) is an important step in the diagnostic process. But are these sonographic features equally reliable in every accessible joint under real-life conditions? We retrospectively analyzed 362 patients with acute arthritis and evaluated the DCS and the degree of PDUS hypervascularization in patients with gout and in those with arthritis other than urate arthritis (non-UA). We classified all joints into the groups small, medium, and large. Sensitivities, specificities, positive and negative predictive values (PPV/NPV), and a binary regression model were calculated. We also evaluated the influence of serum uric acid levels (SUA) on the presence of a DCS in each joint category. Sensitivity of the DCS in gout was 72.5% in the entire cohort, 66.0% in large, 78.8% in medium, and 72.3% in small joints. In wrist joints the DCS sensitivity maxed at 83.3%, with a specificity of 81.8%. The lowest rates of DCS sensitivity were found in gout patients with elbow joint involvement (42.9%). In all joints except metatarsophalangeal joint 1 (MTP-1), the incidence of a DCS increased by the increment of SUA levels above 7.5 mg/dl (p

Background Previous studies have demonstrated typical findings in the ultrasound of salivary glands (USG) in patients with primary Sjogren syndrome (pSS) compared with healthy controls. However, it is unknown, if these findings are only seen in patients with pSS but also in patients with secondary Sjogren syndrome (sSS) or other connective tissue diseases with positive Ro-SSA/La-SSB antibodies. Methods We used an ultrasound score developed by Zhang [1] to investigate salivary glands with a score ranging from 0–48. We compared the score from patients with pSS according the criteria of the American-European Consensus Group (group 1) with patients who fulfilled the clinical criteria (1–4), but were Ro-SSA/La-SSB negative (group 2), with patients who had another rheumatic disease, but had sicca symptoms and were Ro-SSA and/or La-SSB positive (sSS) (group 3), with patients with other rheumatic disease without Ro-SSA or La-SSB antibodies (group 4), with patients with other rheumatic disease with Ro-SSA antibodies but no sicca symptoms (group 5) and with patients with no rheumatic disease (group 6), respectively. We investigated the parotid and the submandibular salivary glands bilaterally. The USG was assessed with a score from 0–48 points with a maximum of 12 points for 4 items each (hyoechoic areas, hyperechoic reflexes, inhomogeneity and distinct organ border). If available the score was correlated with the scintigraphically measured function of the salivary glands. Results We included USG of 92 patients in our study. Group 1 (n=33) had a score of 16.6±11.6; group 2 (n=7) 2.4±3.5; group 3 (n=16) 8.6±9.5; group 4 (n=16) 5.3±7.8; group 5 (n=11) 4.5±6.7 and group 6 (n=9) 1.5±2.3, respectively. The score between group 1 and all other groups was significantly different (p Conclusions USG showed significantly higher scores in patients with pSS, than in patients with sSS or other rheumatic disease. USG as a non invasive investigation might be similarly helpful for the diagnosis of pSS like salivary gland functional tests. USG findings can reliable distinguish between pSS and sSS associated with other rheumatic disease, also if they are positive for Ro-SSA/La-SSB. References Zhang X, Zhang S, He J, Hu F, Liu H, Li J, Zhu J, Li Z. Ultrasonographic evaluation of major salivary glands in primary Sjogren9s syndrome: comparison of two scoring systems. Rheumatology (Oxford). 2015 Sep;54(9):1680–7. Disclosure of Interest None declared

IgG4-related disease (IgG4-RD) are a group of autoinflammatory diseases often presenting as tumor-like lesions because of their infiltrative or mass forming behavior. They are characterized by a typical histology consisting of storiform fibrosis, high numbers of infiltrating IgG4-positive plasma cells, obliterative phlebitis, and a moderate presence of eosinophilic cells. Serum IgG4 levels can be elevated. We present a case of a 57 year-old male patient with immobilizing lower back pain, fever, and night sweats. We diagnosed IgG4-related periaortitis using serum IgG4 levels, abdominal ultrasound, PET/CT, and histology. We successfully treated the patient with glucocorticoids (GC) and azathioprine. Periaortitis is a rare presentation of IgG4-RD and therefore noteworthy. It has to be considered in patients with a retroperitoneal mass.

After entering the blood, bisphosphonates are immediately bound to bone or excreted unchanged by the kidney. During renal excretion about 0.5% of administrated dosage remains in kidney tissue. The renal tissue level of bisphosphonates (RTL) decreases over time and remains at about 0.15% after 3weeks, but the influence of renal insufficiency (RI) is unclear.We investigated the influence of mild to moderate RI on RTL of ibandronate (IBD). First a method for determination of RTL was implemented and validated. We measured RTL in rats with normal renal function (SHAM) and after unilateral nephrectomy (UNX). In each case one SHAM and one UNX groups received one or alternatively 9 times every 3weeks a dosage of 1.5mg/kg IBD. After the last dosage the rats were sacrificed and RTL of IBD were determined.In SHAM-rats IBD concentrations increased from 272.7ng/g kidney after one injection to 428.9ng/g kidney after nine injections (p0.0001). RTL in UNX rats likewise increased significantly (p0.0001) from 289.9ng/g kidney to 520.2ng/g kidney.Our study found a 1.6 fold increase of RTL in SHAM rats and a 1.8 fold increase of RTL in UNX rats after nine versus one injection. As steady state is generally reached after five half-lives we anticipate no further accumulation on continued treatment.

Administration of bisphosphonates (BPs) is an essential supportive treatment for reducing bone-related complications in cancer. Deterioration of renal function is one possible side effect of BPs as well as a clinical feature in multiple myeloma. It has been suggested that the nephrotoxicity of different BPs may differ. We performed a retrospective evaluation of renal function in 201 myeloma patients undergoing myeloablative chemotherapy and treatment with ibandronate (I), pamidronate (P), or zoledronate (Z) for up to 36 months. There was no significant deterioration in mean creatinine clearance (CreaCl) in the entire cohort. The percentage of patients experiencing a decrease in CreaCl ≥ 25 % from baseline was 33.0 % in the I group, 44.4 % in the P group and 21.4 % in the Z group, respectively. CreaCl at baseline (P

Objective.Rituximab (RTX) therapy is a treatment option in patients with refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We investigated the tolerability and clinical efficacy of RTX in a cohort of patients with refractory AAV.Methods.Clinical and safety data of patients with AAV treated with RTX were retrospectively assessed from the data of a German national registry.Results.In total, 58 patients were included in this analysis (50/58 with granulomatosis with polyangiitis; 8/58 with microscopic polyangiitis who received at least 1 cycle, 17 patients who received 2 cycles, and 3 patients who received 3 cycles of RTX). Response was classified as complete and partial in 22 (40%) and in 29 cases (52.7%), respectively. Four patients (7.3%) were classified as nonresponders.Conclusion.RTX was well tolerated with good clinical efficacy in patients with refractory AAV.

Pain relief is an important treatment goal for breast cancer patients with metastatic bone disease and treatment should be associated with a low rate of side effects. This interim analysis of a prospective non-interventional study documents the efficacy and safety of the amino-bisphosphonate ibandronate in the treatment of metastatic bone disease under real-life conditions.For up to 24 weeks 913 breast cancer patients received IV infusions of 6 mg ibandronate every 3-4 weeks or 50 mg of oral ibandronate once daily. Efficacy variables included pain severity, analgesic use, and skeletal-related events; the major safety parameter was renal function, assessed by serum creatinine levels. Subgroup analyses were performed according to pretreatment with bisphosphonates (none, ibandronate, or other bisphosphonates).At baseline, patients with ibandronate pretreatment tended to have lower mean pain scores and lower serum creatinine levels than those pre-treated with other bisphosphonates. Over the observation period, analgesic use did not increase. Among the 712 patients reporting pain at baseline, 70% achieved an improvement in pain severity during treatment with ibandronate, and there was no evidence to suggest relevant differences in mean pain reductions with IV or oral administration of ibandronate or according to prior bisphosphonate treatment. Skeletal-related events were rare (7%). Changes in serum creatinine levels during ibandronate treatment were small and both formulations of ibandronate were rated as well tolerated by physicians and patients.Data from this non-interventional study confirm the analgesic efficacy and safety profile of IV and oral ibandronate under real-life conditions.

Background: Churg–Strauss syndrome (CSS) is a rare systemic vasculitis. Case series with a focus on neurologic involvement are not common. With this study, we intended to evaluate the frequency and types of neurologic manifestations and complications at time of diagnosis and during follow-up of patients with CSS. Methods: In this monocentric study, consecutive patients of our hospital with first diagnosis of CSS based on the criteria of the American College of Rheumatology were included between 2001 and 2007. Each patient underwent a periodic follow-up with clinical and electrophysiologic examination. Data were obtained prospectively. Results: Fourteen patients were included. All patients had a hypereosinophilia and a history of asthma. Twelve of 14 patients had a neurologic involvement, mainly as an acute or subacute multiplex mononeuropathy (eight patients) or an axonal polyneuropathy (three patients). Three patients suffered from a neuropathy of cranial nerves, and two patients had a cerebral infarct. Mean follow-up period was 31 months. With immunosuppressive therapy, 13 patients had no additional neurologic complications, one patient suffered from a cerebral infarct. Initial neurologic symptoms as a result of peripheral neuropathy improved, but sequelae of axonal damage were persistently detectable. Conclusions: Even at time of diagnosis of a CSS, neurologic manifestations are common, especially as a multiplex mononeuropathy. With a consequent immunosuppressive therapy, new neurologic complications can be avoided for the most part.