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Um die Telemedizin erfolgreich in den rheumatologischen Alltag zu integrieren, sind sowohl die Patienten- als auch Arztperspektive wichtig. Hierzu wurde eine ausfuhrliche Studie mittels webbasierter Umfrage durch die Arbeitsgemeinschaft Junge Rheumatologie der Deutschen Gesellschaft fur Rheumatologie (DGRh) und die Deutsche Rheuma-Liga Bundesverband e. V. durchgefuhrt. Mittels Subgruppenanalyse der Daten im Hinblick auf die Videosprechstunde galt es nun herauszufinden, welche Anforderungen und Wunsche unter den Patienten/innen und Arzte/innen an die Videosprechstunde gestellt wurden. Die prospektive Umfrage wurde uber die sozialen Medien, QR-Code und E‑Mail verteilt. Es wurden deskriptive Statistiken und Regressionsanalysen in Bezug auf die Videosprechstunde durchgefuhrt und Korrelationen aufgezeigt. Die Daten zeigen eine positive Einstellung zur Videosprechstunde sowohl aufseiten der Patienten/innen (n = 299) als auch der Rheumatologen/innen (n = 129) auf. Eine Korrelation zwischen Alter und positiver Meinung zur Videosprechstunde zeigte sich unter den Patienten/innen (r = 0,161, p = 0,006), insbesondere bei den weiblichen Patienten fand sich mit zunehmendem Alter ein positiver Zuspruch fur die Videosprechstunde (r = 0,244, p

Reasons of mon- and oligoarthritis are heterogeneous. The diagnostic approach includes a detailed medical anamnesis, physical examination and imaging (conventional X-ray, sonography, MRI and, CT). Analysis of the synovial fluid is required in suspected septic arthritis and frequently helps in diagnosis and differential diagnosis of crystal arthropathies. Dual-energy-CT (DECT) detects sodium urate crystals and can replace joint puncture in some cases. In addition to crystal arthropathies and septic arthritis, differential diagnosis of mon-/oligoarthritis includes reactive arthritis, arthrosis and monarthritic courses of SpA/PsA. A rheumatologist should be consulted particularly in the case of persistent monarthritides, in order to initiate a specific therapy to prevent secondary damage.

Objective Despite increased physician’s awareness and improved diagnostic and serological testing in the recent years, the interval between the initial symptoms and the diagnosis of Systemic lupus erythematosus (SLE) is still very long. Our aim was to study this delay and its association to the outcome of the disease. Methods Information on demographics, onset of first symptoms, first physicians visit and time of diagnosis was assessed by self-reported questionnaires among SLE patients in Germany (LuLa cohort, n = 585) in the year 2012. Disease activity (Systemic Lupus Activity Questionnaire; SLAQ), disease related damage (Brief Index of Lupus Damage; BILD), health related quality of life (Short Form 12) and fatigue (FSS) were chosen as proxies for outcome. Linear regression analysis was used to analyze the association of the delay in diagnosis to the outcome, adjusted for age, disease duration and sex. Results Mean duration between the onset of symptoms and the diagnosis of SLE was 47 months (SD 73). The longer the time to diagnosis, the higher the disease activity (β = 0.199, p Conclusion In systemic lupus erythematosus, longer time to diagnosis was associated with worse outcome. Concepts in care with the intention to shorten the time to diagnosis are needed to improve the long-term outcome of the disease.

An international consensus on antineutrophil cytoplasm antibodies (ANCA) testing in eosinophilic granulomatosis with polyangiitis (EGPA) is presented. ANCA, specific for myeloperoxidase (MPO), can be detected in 30-35% of patients with EGPA. MPO-ANCA should be tested with antigen-specific immunoassays in any patient with eosinophilic asthma and clinical features suggesting EGPA, including constitutional symptoms; purpura; polyneuropathy; unexplained heart, gastrointestinal, or kidney disease; and/or pulmonary infiltrates or hemorrhage. A positive MPO-ANCA result contributes to the diagnostic workup for EGPA. Patients with MPO-ANCA-associated EGPA have vasculitis features, such as glomerulonephritis, neuropathy, and skin manifestations, more frequently than patients with ANCA-negative EGPA. However, the presence of MPO-ANCA is neither sensitive nor specific enough to identify whether a patient should be subclassified as having "vasculitic" or eosinophilic" EGPA. At present, ANCA status cannot guide treatment decisions, that is, whether cyclophosphamide, rituximab, or mepolizumab should be added to conventional glucocorticoid treatment. In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset.

Haufig werden uns als Rheumatologen Patienten mit einer Muskelschwache und Erhohung der Kreatinkinase (CK) vorgestellt. Nicht immer kann eine Myositis als Ursache der Beschwerden festgestellt werden. Wir prasentieren 2 Kasuistiken aus unserer Klinik, deren Diagnose erst mithilfe der Muskelbiopsie gestellt werden konnte: Im ersten Fall handelt es sich um einen Patienten mit einer Muskelschwache, einem pathologischen Gewichtsverlust und einer deutlichen CK-Erhohung. Mithilfe der Muskelbiopsie konnte die Diagnose einer immunvermittelten nekrotisierenden Myopathie bedingt durch HMG-CoA-Reduktase-Autoantikorper nach Statineinnahme gestellt werden. Die zweite Patientin prasentierte sich mit krampfartigen und brennenden Muskelschmerzen sowie einer Schwache der Extremitaten ohne relevante CK-Erhohung. Auch hier erfolgte die histologische Untersuchung eines betroffenen Muskels, in der sich ein Myoadenylat-Deaminase-Mangel zeigte. Dieser konnte in einer genetischen Untersuchung bestatigt werden.

Objective Our aim was to study the quality of medical care in patients with systemic lupus erythematosus (SLE) to understand gaps and to analyze the association with outcome of the disease. Methods Information on demographics and medical care was assessed by self-reported questionnaires among SLE patients (LuLa cohort, 2011, n = 580). In total, 21 aspects of medical care were analyzed. Univariate analysis selected 10 predictor variables for further analysis: (1) urine examination and (2) blood test in the previous year, (3) taking antimalarials, (4) taking vitamin D and calcium if the dosage of prednisolone was greater than 7.5 mg/day, counseling regarding (5) lipid metabolism, (6) vaccination, and (7) blood pressure, and treatment of the comorbidities (8) hypertension, (9) osteoporosis and (10) lipid metabolism disorder. The association of these 10 items with the outcome of the disease, assessed in 2015, was analyzed by linear regression analysis, adjusted for age, disease duration and sex. Results On average six of the 10 items were met (±1.7). Receiving more clinical care in 2013 was predictive for low disease activity (SLAQ, p = 0.024, β = –0.104, corr. R2 = 0.048), low progress in disease-related damage (Delta Brief Index of Lupus Questionnaire, p = 0.048, β = –0.132, corr. R2 = 0.036) and high health-related quality of life (SF-12 physical, p = 0.035, β = 0.100, corr. R2 = 0.091) in 2015. Conclusion Our study illustrates a link between the quality of care and the SLE outcome parameters disease activity, disease-related damage and quality of life. Consistent considerations of these care parameters, which are recommended in several management guidelines, could therefore be a good approach to improve the outcome of patients with SLE.

Objective The aim of this study was to identify factors associated with impaired work productivity and impaired daily activities in patients with systemic lupus erythematosus (SLE). Methods The LuLa study is a longitudinal patient-reported study. Beyond sociodemographic data, work productivity, daily activities and fatigue, several other clinical outcome parameters (e.g. mental health–related quality of life and physical functioning, disease activity, damage and pain) were surveyed with validated questionnaires. The effects of confounders on work productivity (WPAI 2) and daily activity domains (WPAI 4) were studied by multivariate regression analysis. Results A total of 585 patients completed the questionnaire of whom 259 were employed and analysed. The median impairment in work productivity (WPAI 2) was 20% (Q1–3 0–40), and the median impairment in daily activities (WPAI 4) was 30% (Q1–3 10–50%). Multivariate regression analysis revealed that fatigue, pain, disease activity and health-related quality of life affected WPAI 2 and 4. Furthermore, we observed distinct synergistic effects of fatigue, disease activity and pain on both work productivity and daily activities: a higher impact of fatigue was associated with the reported extent of pain or disease activity. Conclusion In employed patients with SLE, impaired work productivity and impaired daily activities were frequently reported. Fatigue, pain, disease activity and health-related quality of life demonstrated a detrimental impact, with a synergistic effect of fatigue, disease activity and pain. Hence, both optimized pain management and targeted immunomodulatory therapy are important for preserving active participation in life among patients with fatigue.

In order to successfully integrate telemedicine into the daily routine of rheumatology, both the patient's and the physician's perspective are important. For this purpose, a detailed study by means of a web-based survey was conducted by the Working Group Young Rheumatology (AGJR) of the German Society for Rheumatology (DGRh) and the German Rheumatism League National Association. By means of subgroup analysis of the data regarding video consultation, the aim was now to find out which requirements and wishes patients and physicians have for video consultations.The prospective survey was distributed via social media, QR code and email. Descriptive statistics and regression analysis related to video consultation were performed and correlations were shown.The data indicated positive attitudes toward video consultation on the part of both patients (n = 299) and rheumatologists (n = 129). A correlation between age and positive opinion of the video consultation was found among the patients (r = 0.161, p = 0.006), especially among female patients a positive approval of the video consultation was found with increasing age (r = 0.244, p 0.001 to male patients: r = -0.190, p = 0.145). Regarding the travelling time to the treating rheumatologist, male patients found the video consultation more attractive with increasing travelling time (r = 0.229, p = 0.078). With respect to the wishes of patients and physicians, video consultation should be used primarily for follow-up or emergency appointments. Video consultation for initial appointments, on the other hand, was very rarely mentioned.During the COVID 19 pandemic, video consultation was increasingly popular among rheumatology patients as well as among rheumatologists.EINLEITUNG: Um die Telemedizin erfolgreich in den rheumatologischen Alltag zu integrieren, sind sowohl die Patienten- als auch Arztperspektive wichtig. Hierzu wurde eine ausführliche Studie mittels webbasierter Umfrage durch die Arbeitsgemeinschaft Junge Rheumatologie der Deutschen Gesellschaft für Rheumatologie (DGRh) und die Deutsche Rheuma-Liga Bundesverband e. V. durchgeführt. Mittels Subgruppenanalyse der Daten im Hinblick auf die Videosprechstunde galt es nun herauszufinden, welche Anforderungen und Wünsche unter den Patienten/innen und Ärzte/innen an die Videosprechstunde gestellt wurden.Die prospektive Umfrage wurde über die sozialen Medien, QR-Code und E‑Mail verteilt. Es wurden deskriptive Statistiken und Regressionsanalysen in Bezug auf die Videosprechstunde durchgeführt und Korrelationen aufgezeigt.Die Daten zeigen eine positive Einstellung zur Videosprechstunde sowohl aufseiten der Patienten/innen (n = 299) als auch der Rheumatologen/innen (n = 129) auf. Eine Korrelation zwischen Alter und positiver Meinung zur Videosprechstunde zeigte sich unter den Patienten/innen (r = 0,161, p = 0,006), insbesondere bei den weiblichen Patienten fand sich mit zunehmendem Alter ein positiver Zuspruch für die Videosprechstunde (r = 0,244, p 0,001 zu männlichen Patienten: r = −0,190, p = 0,145). Bezüglich der Fahrtzeit bis zum behandelnden Rheumatologen tendierten die männlichen Patienten mit zunehmender Fahrzeit zur Videosprechstunde (r = 0,229, p = 0,078), dies war jedoch nur schwach positiv. Hinsichtlich der Wünsche von Patienten/innen und Ärzten/innen sollte die Videosprechstunde v. a. für Folge- oder Notfalltermine genutzt werden. Eine Videosprechstunde für die Erstvorstellungen war hingegen nur sehr selten gewünscht.Während der COVID-19-Pandemie hat die Videosprechstunde zunehmenden Zuspruch unter den rheumatologischen Patienten/innen als auch unter den behandelnden Rheumatologen/innen erhalten.

Reasons of mon- and oligoarthritis are heterogeneous. The diagnostic approach includes a detailed medical anamnesis, physical examination and imaging (conventional X-ray, sonography, MRI and, CT). Analysis of the synovial fluid is required in suspected septic arthritis and frequently helps in diagnosis and differential diagnosis of crystal arthropathies. Dual-energy-CT (DECT) detects sodium urate crystals and can replace joint puncture in some cases. In addition to crystal arthropathies and septic arthritis, differential diagnosis of mon-/oligoarthritis includes reactive arthritis, arthrosis and monarthritic courses of SpA/PsA. A rheumatologist should be consulted particularly in the case of persistent monarthritides, in order to initiate a specific therapy to prevent secondary damage.

ObjectiveTo analyse the impact of the COVID-19 pandemic on rheumatic patients’ and rheumatologists’ usage, preferences and perception of digital health applications (DHAs).MethodsA web-based national survey was developed by the Working Group Young Rheumatology of the German Society for Rheumatology and the German League against Rheumatism. The prospective survey was distributed via social media (Twitter, Instagram and Facebook), QR code and email. Descriptive statistics were calculated, and regression analyses were performed to show correlations.ResultsWe analysed the responses of 299 patients and 129 rheumatologists. Most patients (74%) and rheumatologists (76%) believed that DHAs are useful in the management of rheumatic and musculoskeletal diseases (RMDs) and felt confident in their own usage thereof (90%; 86%). 38% of patients and 71% of rheumatologists reported that their attitude had changed positively towards DHAs and that their usage had increased due to COVID-19 (29%; 48%). The majority in both groups agreed on implementing virtual visits for follow-up appointments in stable disease conditions. The most reported advantages of DHAs were usage independent of time and place (76.6%; 77.5%). The main barriers were a lack of information on suitable, available DHAs (58.5%; 41.9%), poor usability (42.1% of patients) and a lack of evidence supporting the effectiveness of DHAs (23.2% of rheumatologists). Only a minority (ConclusionThe COVID-19 pandemic instigated an increase in patients’ and rheumatologists’ acceptance and usage of DHAs, possibly introducing a permanent paradigm shift in the management of RMDs.

Purpose Our aim was to study the delay from the onset of symptoms to the diagnosis of systemic lupus erythematosus (SLE) and its association to the outcome of the disease. Methods Information on demographics, onset of first symptoms, first physicians visit and time of diagnosis was assessed by self-reported questionnaires among SLE patients in Germany in 2010 (LuLa cohort, n=585). Disease activity (Systemic Lupus Activity Questionnaire; SLAQ), disease related damage (Brief Index of Lupus Damage; BILD) and health related quality of life were chosen as relevant proxies for outcome. Linear regression analysis was used to analyze the association to the outcome of the disease, adjusted for age, disease duration and sex. Results Mean reported duration between the onset of symptoms and the diagnosis of SLE was 45.7 months (SD 72.6), including a mean duration of 13.2 month (SD 40.9) between the onset of symptoms and the first physicians visit. In our cohort, the mean disease duration was 17.7 years (SD 7.89). A delayed diagnosis was associated with high disease activity (SLAQ, p Conclusion The time to diagnosis was associated with a worse outcome in systemic lupus erythematosus, assessed by self-reported questionnaires for disease activity, disease-related damage and quality of life, unaffected by the organ involvement at the time of diagnosis. An early diagnosis should therefore be strived to improve the long-term outcome of the disease. German Clinical Trial Register, www.germanctr.de, DRKS00011052 Acknowledgement The LuLa study is supported by unrestricted grants from GlaxoSmithKline and UCB Pharma.

A few decades ago, the therapy goal of patients with systemic lupus erythematosus (SLE) was survival and the prevention of organ failure. Today, clinical remission and low disease activity are believed to be the optimal therapeutic targets. These aims are difficult to reach for many patients, but they still do not address the health-related quality of life (QoL) that is significantly impaired in SLE patients. Even in the state of remission, QoL and fatigue are insufficient controlled. Thus, patient-oriented research is essential to design new strategies for the management of lupus patients. The INTEGRATE project analyses the patients’ and physicians’ perspectives to pave the way to design an innovative therapeutic strategy for lupus and focuses on the multifaceted dimensions of the disease burden. Shared decision making (SDM) could include the patient’s perspective of SLE to treatment strategy and consider QoL and the burden of lupus into the process of therapy decision.

Background:Digital health applications (DHAs) are gaining influence and promise great potential for the monitoring and management of rheumatic and musculoskeletal diseases (RMDs).Objectives:To analyse the impact of the COVID-19 pandemic on RMD patients’ and rheumatologists’ usage, preferences, and perception of digital health applications (DHAs) in Germany.Methods:A web-based national survey was developed by the Working Group Young Rheumatology of the German Society for Rheumatology and the German League against Rheumatism. The prospective survey was distributed via social media, QR-code, and email. Descriptive statistics were calculated, and regression analyses were performed to show correlations.Results:We analysed the responses of 299 patients and 129 rheumatologists. Most patients (74%) and rheumatologists (76%) believed that DHAs are useful in the management of RMDs and felt confident in their own usage thereof (90%; 86%). 38% of patients and 71% of rheumatologists reported that their attitude had changed positively towards DHAs and that their usage had increased due to COVID-19 (29%; 48%).Usage and recommendation of DHAs for both groups are shown in Figure 1:Figure 1.Usage or recommendation of digital health applications. Patients and rheumatologists were asked to indicate the specific digital health applications (DHAs) they used or were recommended.The majority in both groups agreed on implementing virtual visits for follow-up appointments in stable disease conditions. The most reported advantages of DHAs were usage independent of time and place (76.6%; 77.5%). The main barriers were a lack of information on suitable, available DHAs (58.5%; 41.9%), poor usability (42.1% of patients) and a lack of evidence supporting the effectiveness of DHAs (23.2% of rheumatologists) (Table 1).Table 1.Advantages and Barriers of DHA, n (%).AdvantagesBarriersPatientsRheumatologistsPatientsRheumatologistsLocation-Independence229 (76.6)100 (77.5)Too little information175 (58.5)54 (41.9)Time-independence223 (74.6)94 (72.9)Too little evidence of benefits36 (12.0)30 (23.3)Detailed documentation97 (32.4)47 (36.4)Poor quality of current apps47 (15.7)29 (22.5)Cost saving95 (31.8)37 (28.7)Concernsabout data protection52 (17.4)25 (19.4)More information88 (29.4)38 (29.5)Lack of usability126 (42.1)17 (13.2)Independenceof doctors+36 (12.0)-Lack of accessibility4 (1.3)-More flexibility107 (36.8)77 (59.7)High costs4 (1.3)23 (17.8)Preparationfor discussion+46 (15.4)-No suitable equipment17 (5.7)11 (8.5)No advantages at all18 (6.0)1 (0.8)Lack of user competenceNo Need9 (3.0)39 (13.0)-12 (9.3)Patients and rheumatologists were asked about the advantages and barriers of DHAs. Multiple answers were allowed. Patients had two additional potential advantages and potential barriers to choose from*.Only a minority (Conclusion:The COVID-19 pandemic instigated an increase in patients’ and rheumatologists’ acceptance and usage of DHAs, possibly introducing a permanent paradigm shift in the management of RMDs.Acknowledgements:The authors thank the following persons and societies for their great effort, distributing the online survey: P.Aries, A.Hueber, E.Feist, C.Fiehn, P.Korsten, I.Kötter, F.Mühlensiepen, A.Pfeil, M.Rudwaleit, M.Welcker, S.Zinke, Deutsche Vereinigung Morbus Bechterew e.V., Deutsche Rheuma-Liga Bundesverband e. V., Sklerodermie Selbsthilfe e.V.Disclosure of Interests:Anna Kernder: None declared, Harriet Morf: None declared, Philipp Klemm: None declared, Diana Vossen Speakers bureau: Novartis, Abbvie, Amgen, Consultant of: Abbvie Deutschland GmbH & Co. KG, Bristol-Myer Squibb, Celgene GmbH, Gilead Sciences Inc., Lilly Deutschland GmbH, Medac GmbH, Novartis Pharma GmbH, Pfizer Deutschland GmbH, UCB Pharma GmbH, Grant/research support from: Pfizer, Abbvie, Marco Meyer Consultant of: Medac, Isabell Haase Speakers bureau: Medac, Consultant of: Medac, Grant/research support from: UCB, Abbvie, BMS, Johanna Mucke Speakers bureau: AbbVie Deutschland GmbH & Co. KG, Amgen, Bristol-Myers Squibb, Chugai Pharma Germany GmbH, Celgene GmbH, Gilead Sciences Inc., GlaxoSmithKline, Janssen-Cilag GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Deutschland GmbH and UCB Pharma GmbH., Consultant of: AbbVie Deutschland GmbH & Co. KG, Amgen, Bristol-Myers Squibb, Chugai Pharma Germany GmbH, Celgene GmbH, Gilead Sciences Inc., GlaxoSmithKline, Janssen-Cilag GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Deutschland GmbH and UCB Pharma GmbH., Arnd Kleyer Shareholder of: yes, Speakers bureau: Lilly, Novartis, Consultant of: Abbvie, Lilly, Novartis BMS, Gilead,Janssen, Grant/research support from: Lilly, Novartis, Gilead,, Philipp Sewerin Consultant of: AbbVie, Amgen, Axiom Health, Biogen, Bristol-Myers Squibb, Celgene, Chugai Pharma Marketing Ltd./Chugai Europe, Deutscher Psoriasis-Bund, Fresenius Kabi, Gilead Sciences, Hexal Pharma, Janssen-Cilag, Johnson & Johnson, Lilly, Medi-login, Mediri GmbH, Novartis Pharma, Onkowissen GmbH, Pfizer, Roche Pharma, Rheumazentrum Rhein-Ruhr, Sanofi-Genzyme, Swedish Orphan Biovitrum, and UCB, Grant/research support from: AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Bundesministerium fuer Bildung und Forschung (BMBF), Deutsche Forschungsgesellschaft (DFG), Deutscher Psoriasis-Bund, Fresenius Kabi, Gilead Sciences, Hexal Pharma, Janssen-Cilag, Lilly, Novartis Pharma, Pfizer, Rheumazentrum Rhein-Ruhr, Roche Pharma, Sanofi-Genzyme, and UCB, Gerlinde Bendzuck: None declared, Sabine Eis: None declared, Johannes Knitza Consultant of: Abbvie, Novartis, Lilly, Medac, BMS, Sanofi, Amgen, Gilead, UCB, ABATON, GSK, Grant/research support from: Novartis, UCB, Thermofisher, Sanofi, Martin Krusche Speakers bureau: Lilly, Medac, Novartis, Roche/Chugai, Consultant of: Abbvie, Lilly, Gilead, Medac, Novartis, Sobi, BMS, Amgen, GSK, Grant/research support from: Sanofi

Background:Evidence on the efficacy of Mepolizumab (MEPO) in Eosinophilic Granulomatosis with Polyangiitis (EGPA) is scarce [1].Objectives:To assess the efficacy and safety of MEPO in real-life clinical practice.Methods:We retrospectively included patients diagnosed with EGPA and treated with MEPO (100 or 300 mg/month). MEPO efficacy was evaluated in the first 12 months in terms of systemic disease and asthma control. The occurrence of any adverse event (AE) was recorded.Results:142 patients were included (38% males; median age 46.4 (IQR 36.7-54.4); 110 and 32 on MEPO 100 and 300 mg/month, respectively). General, ear-nose-throat, pulmonary, and neurological symptoms significantly decreased during treatment (table 1). MEPO accounted for a significant reduction in the BVAS (figure 1) and for a steroid sparing effect (figure 2). The proportion of patients with asthma attacks decreased by 90% at 12 months compared to t0, and asthma-related emergency accesses dropped from 17.4% to 2.3%. Overall, 21.1% of patients had a non-serious AE.Table 1.Control of clinical symptomsMEPO beginning (t0)3 monthsp-value(t3 vs t0)6 monthsp-value(t6 vs t0)12 monthsp-value(t12 vs t0)N obsN=142N=135N=123N=89General symptoms40 (28.2%)17 (12.6%)19 (15.5%)13 (14.6%)0.002Cutaneous manifestations13 (9.2%)6 (4.4%)0.0085 (4.1%)0.0254 (4.5%)0.180ENT manifestations106 (74.7%)52 (38.5%)44 (35.8%)29 (32.6%)Pulmonary manifestations130 (91.6%)59 (43.7%)39 (31.7%)28 (31.5%)Cardiac manifestations6 (4.2%)2 (1.5%)0.0832 (1.6%)0.08300.157Intestinal manifestations10 (7.0%)1 (0.7%)0.0054 (3.3%)0.0593 (3.4%)0.059Renal manifestations5 (3.5%)3 (2.2%)0.41400.0461 (1.1%)0.317Neurological manifestations36 (25.4%)22 (16.3%)0.01218 (14.6%)0.00310 (11.2%)0.035Figure 1.Changes in BVASFigure 2.Steroid treatmentConclusion:MEPO effectively controlled systemic and respiratory EGPA symptoms in a large European cohort, with no major safety concerns.References:[1]Wechsler et al. MEPO or Placebo for Eosinophilic Granulomatosis with Polyangiitis. NEJM. 2017Disclosure of Interests:Alessandra Bettiol: None declared, Maria Letizia Urban: None declared, Federico Alberici: None declared, Carlo Agostini: None declared, Chiara Baldini: None declared, Enrica Bozzolo: None declared, Paolo Cameli: None declared, Nunzio Crimi: None declared, Stefano Del Giacco: None declared, Allyson Egan: None declared, Georgina Espigol-Frigole Consultant of: Roche and Janssen, Mara Felicetti: None declared, Marco Folci: None declared, Paolo Fraticelli: None declared, Marcello Govoni: None declared, Anna Kernder Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Carlo Lombardi: None declared, Giuseppe Lopalco: None declared, Claudio Lunardi: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Frank Moosig: None declared, Simone Negrini: None declared, Thomas Neumann: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Giuseppe Paolazzi: None declared, paola parronchi: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Vito Racanelli: None declared, Carlo Salvarani: None declared, Maxime Samson: None declared, Jan Schroeder: None declared, Savino Sciascia: None declared, Renato A. Sinico: None declared, Benjamin Terrier: None declared, Paola Toniati: None declared, Domenico Prisco: None declared, Augusto Vaglio: None declared, Giacomo Emmi: None declared

Background Systemic lupus erythematosus (SLE) is a chronic disease, which is still associated with significant morbidity and mortality1. Recommendations for the management of SLE patients exist2-5, but information on its implementation and the resulting impact on long-term outcome remain unclear. Objectives Our aim was to study the quality of SLE medical care in Germany to understand gaps and to analyze the association to long-term outcome parameters. Methods In the LuLa-study information on demographics, clinical and medical care parameters are assessed annually by self-reported questionnaires among a representative sample of SLE patients in Germany (LuLa cohort, n=572). In 2013 additional questions on the management of care, as mentioned in current guidelines and recommendations, were surveyed. Ten items predicting a good clinical care (quality measures) were evaluated and an overall score with a minimum of 0 points and a maximum of 10 points was calculated. The ten items are taking antimalarials, osteoporosis protection at a dose above 7.5mg prednisolone equivalent per day or taking ≤ 7.5mg per day, vaccination, blood pressure, fat metabolism counseling, urine examination and blood test once a year, treatment of comorbidity fat metabolism disorder, osteoporosis and hypertension. Health related quality of life (Short Form Survey, SF-12/36), damage (Brief Index of Lupus Damage, BILD) and disease activity (Systemic Lupus Activity Questionnaire, SLAQ) were chosen as relevant proxies for long-term outcome. Using linear regression, we examined the relationship between the quality measures and outcome parameters, adjusted for age, disease duration and gender. Results 65.5% of the patients consulted a rheumatologist as a main contact for their disease. On average 6.1 points of the 10 quality measures were met (SD 1.7). The fulfillment of these quality measures varied between 22.8% (fat metabolism counseling) and 97.6% (osteoporosis protection at a dose above 7.5mg prednisolone equivalent per day or ≤ 7.5mg per day). Fulfilling more clinical care items in 2013 was predictive for high disease-related quality of life (SF-36, p=0.004), low progress in disease-related damage (BILD, p=0.048) and low disease activity (SLAQ, p=0.046) in the subsequent years. Conclusion Our study illustrates a strong link between the quality of care and important SLE outcome parameters: quality of life, disease-related damage and disease activity assessed by a self-reported questionnaire. Consistent considerations of these care parameters, which are recommended in several management guidelines, yield a positive effect on outcome. An interdisciplinary approach with general practitioners and other specialists is certainly beneficial and warranted. German Clinical Trial Register, www.germanctr.de, DRKS00011052 References [1] Borchers, A. T., Keen, C. L., Shoenfeld, Y. & Gershwin, M. E. Surviving the butterfly and the wolf: mortality trends in systemic lupus erythematosus. Autoimmun. Rev. 3, 423–453 (2004). [2] Bertsias,G. et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann. Rheum. Dis. 67, 195–205 (2008). [3] Mosca, M. et al. European League Against Rheumatism recommendations for monitoring patients with systemic lupus erythematosus in clinical practice and in observational studies. Ann. Rheum. Dis. 69, 1269–1274 (2010). [4] Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 42, 1785–1796 (1999). Disclosure of Interests Anna Kernder Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Jutta Richter Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Rebecca Fischer-Betz Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Borgi Winkler-Rohlfing: None declared, Matthias Schneider Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Speakers bureau: Chugai, Gamal Chehab Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study.

Background:Patients with systemic lupus erythematosus (SLE), even compared to those with other rheumatic diseases, are thought to often experience a long delay from the onset of symptoms to diagnosis.Objectives:Our aim was to study the association of this delay to the long-term outcome of the disease.Methods:Information on demographics, onset of first symptoms, first physicians visit, time of diagnosis and organ involvement was assessed by self-reported questionnaires among SLE patients in Germany in 2011 (LuLa cohort, n=585). Disease related damage (Brief Index of Lupus Damage; BILD), disease activity (Systemic Lupus Activity Questionnaire; SLAQ) and health related quality of life (SF-12) were chosen as proxies for outcome. The association to the outcome of the disease was analyzed by linear regression analysis, adjusted for age, disease duration, organ involvement and sex.Results:In our cohort, the mean reported duration between the onset of symptoms and the diagnosis of SLE was 46 months (SD 73), which includes 13 months (SD 41) between the onset of symptoms and the first physicians visit. The participating patients were diagnosed between 1960 and 2004.Linear regression analysis revealed that longer time to diagnosis was associated with (i) higher disease activity (SLAQ, pConclusion:A delay in diagnosis was associated with a worse outcome in SLE (disease activity, disease-related damage and health-related quality of life). Therefore, an early diagnosis seems to be important to improve the long-term outcome of the disease. It will be interesting to see whether adopting the new EULAR/ACR 2019 classification criteria can contribute to a faster diagnosis and a better outcome in consequence.The LuLa study is supported by unrestricted grants from GlaxoSmithKline and UCB Pharma.Disclosure of Interests:Anna Kernder Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Jutta Richter Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Rebecca Fischer-Betz Consultant of: UCB, Speakers bureau: Abbvie, Amgen, Biogen, BMS, Celgene, Chugai, GSK, Janssen, Lilly, Medac, MSD, Novartis, Roche, UCB, Pfizer., Borgi Winkler-Rohlfing: None declared, Martin Aringer Consultant of: Boehringer Ingelheim, Roche, Speakers bureau: Boehringer Ingelheim, Roche, Matthias Schneider Grant/research support from: GSK, UCB, Abbvie, Consultant of: Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, Speakers bureau: Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, Gamal Chehab Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study.

Histaminergic (HA) neurons located in the tuberomamillary nucleus (TMN) of the posterior hypothalamus fire exclusively during waking and support many physiological functions. We investigated the role of the endovanilloid N-oleoyldopamine (OLDA) in TMN, where dopamine synthesis and its conjugation with oleic acid likely occur. We show that several known targets of OLDA including TRPV1 and cannabinoid receptors are expressed in HA neurons. In contrast to capsaicin, which failed to increase firing of HA neurons in TRPV1 knockout mice (TRPVI KO), OLDA was still able to induce excitation. This excitation was not sensitive to the blockade of cannabinoid receptors 1 and 2 and could result from OLDA interaction with GPR119, as the ligand of GPR119, oleoylethanolamide (OEA), also increased the firing of HA neurons. However, we ruled out this possibility as OEA- (but not OLDA-) excitation was abolished by the PPAR (peroxisome proliferator activated receptor) alpha antagonist MK886. The dopamine uptake blocker nomifensine blanked OLDA-excitation and dopamine receptor antagonists abolished the OLDA action in TRPV1 KO mice. Therefore OLDA excites HA neurons through multiple targets suggesting a central role of the histaminergic system in the behavioral stimulation seen after systemic OLDA application.

Breathing and vigilance are regulated by pH and CO2 levels in the central nervous system. The hypocretin/orexin (Hcrt/Orx)- and histamine (HA)-containing hypothalamic neurons synergistically control different aspects of the waking state. Acidification inhibits firing of most neurons but these two groups in the caudal hypothalamus are excited by hypercapnia and protons, similar to the chemosensory neurons in the brain stem. Activation of hypothalamic wake-on neurons in response to hypercapnia, seen with the c-Fos assay, is supported by patch-clamp recordings in rodent brain slices: Hcrt/Orx and HA neurons are excited by acidification in the physiological range (pH from 7.4 to 7.0). Multiple molecular mechanisms mediate wake-promoting effects of protons in HA neurons in the tuberomamillary nucleus (TMN): among them are acid-sensing ion channels, Na(+),K(+)-ATPase, group I metabotropic glutamate receptors (mGluRI). HA neurons are remarkably sensitive to the mGluRI agonist DHPG (threshold concentration 0.5 µM) and mGluRI antagonists abolish proton-induced excitation of HA neurons. Hcrt/Orx neurons are excited through block of a potassium conductance and release glutamate with their peptides in TMN. The two hypothalamic nuclei and the serotonergic dorsal raphe cooperate toward CO2/acid-induced arousal. Their interactions and molecular mechanisms of H(+)/CO2-induced activation are relevant for the understanding and treatment of respiratory and metabolic disorders related to sleep-waking such as obstructive sleep apnea and sudden infant death syndrome.

The histaminergic neurons in the tuberomamillary nucleus (TMN) of the posterior hypothalamus are involved in the control of arousal. These neurons are sensitive to hypercapnia as has been shown in experiments examining c-Fos expression, a marker for increased neuronal activity. We investigated the mechanisms through which TMN neurons respond to changes in extracellular levels of acid/CO(2). Recordings in rat brain slices revealed that acidification within the physiological range (pH from 7.4 to 7.0), as well as ammonium chloride (5 mM), excite histaminergic neurons. This excitation is significantly reduced by antagonists of type I metabotropic glutamate receptors and abolished by benzamil, an antagonist of acid-sensing ion channels (ASICs) and Na(+)/Ca(2+) exchanger, or by ouabain which blocks Na(+)/K(+) ATPase. We detected variable combinations of 4 known types of ASICs in single TMN neurons, and observed activation of ASICs in single dissociated TMN neurons only at pH lower than 7.0. Thus, glutamate, which is known to be released by glial cells and orexinergic neurons, amplifies the acid/CO(2)-induced activation of TMN neurons. This amplification demands the coordinated function of metabotropic glutamate receptors, Na(+)/Ca(2+) exchanger and Na(+)/K(+) ATPase. We also developed a novel HDC-Cre transgenic reporter mouse line in which histaminergic TMN neurons can be visualized. In contrast to the rat, the mouse histaminergic neurons lacked the pH 7.0-induced excitation and displayed only a minimal response to the mGluR I agonist DHPG (0.5 μM). On the other hand, ammonium-induced excitation was similar in mouse and rat. These results are relevant for the understanding of the neuronal mechanisms controlling acid/CO(2)-induced arousal in hepatic encephalopathy and obstructive sleep apnoea. Moreover, the new HDC-Cre mouse model will be a useful tool for studying the physiological and pathophysiological roles of the histaminergic system.