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Current research in the field of systemic lupus erythematosus (SLE) and pregnancy focuses on predictors of adverse pregnancy outcomes, the safety and efficacy of hydroxychloroquine (HCQ) in pregnancy and the importance of preconception counselling. In particular, the prospective predictors of pregnancy outcome: biomarkers in antiphospholipid antibody syndrome and SLE (PROMISSE) study adds to the understanding of risk factors for adverse outcomes. There is increasing evidence of the numerous benefits associated with continuing HCQ treatment in pregnancy and for the use of low-dose acetylsalicylic acid in the prevention of preeclampsia. The European League Against Rheumatism (EULAR) has published evidence-based recommendations for the treatment of women with SLE and/or antiphospholipid syndrome before, during and after pregnancy. Rheumatologists caring for women with SLE should be familiar with the current state of knowledge in order to help optimize the management and thus the outcome of pregnancy in their patients.

Entzundlich-rheumatische Erkrankungen betreffen bevorzugt Frauen im gebarfahigen Alter. Immunologische Veranderungen konnen sich in positiver oder negativer Form auf die mutterliche Erkrankung auswirken. Die meisten Frauen konnen bei sorgfaltiger medizinischer und geburtshilflicher Betreuung eine erfolgreiche Schwangerschaft haben. Dennoch sind Schwangerschaftskomplikationen weiterhin haufiger als bei gesunden Frauen. Schwangerschaften sollten daher in einer inaktiven Krankheitsphase und nach individueller Risikostratifizierung geplant werden. Insbesondere in Bezug auf eine kompatible Therapie ist eine eingehende Information der Patientinnen zur gemeinsamen Entscheidungsfindung notwendig.

Current research in the field of systemic lupus erythematosus (SLE) and pregnancy focuses on predictors of adverse pregnancy outcomes, the safety and efficacy of hydroxychloroquine (HCQ) in pregnancy and the importance of preconception counselling. In particular, the prospective predictors of pregnancy outcome: biomarkers in antiphospholipid antibody syndrome and SLE (PROMISSE) study adds to the understanding of risk factors for adverse outcomes. There is increasing evidence of the numerous benefits associated with continuing HCQ treatment in pregnancy and for the use of low-dose acetylsalicylic acid in the prevention of preeclampsia. The European League Against Rheumatism (EULAR) has published evidence-based recommendations for the treatment of women with SLE and/or antiphospholipid syndrome before, during and after pregnancy. Rheumatologists caring for women with SLE should be familiar with the current state of knowledge in order to help optimize the management and thus the outcome of pregnancy in their patients.

BackgroundThe patient reported Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) includes the six components fatigue, neck, back or hip pain, pain or swelling in other joints, tenderness, morning stiffness severity and duration on a 0-10 scale.ObjectivesTo explore the driving factors for the BASDAI in pregnant patients with axial spondyloarthritis (axSpA).MethodsAnonymized pooled data of the European Network of Pregnancy Registries in Rheumatology (EuNeP) were used. The four participating registries are located in France, Germany, Norway and Switzerland, and collect data of women with child wish, during and after pregnancy prospectively and nationwide on regular time points. For the analysis, women who fulfilled ASAS classification criteria for axSpA and for whom a pregnancy outcome was reported until 12/2019 or 07/2020, depending on the registry, were selected. Mean BASDAI and its components were analysed descriptively.ResultsA total of 332 pregnancies from 304 women with axSpA were eligible. The Norwegian registry contributed half of the pregnancies (50.3%), followed by Germany (26.2%), France (15.4%) and Switzerland (8.1%). Mean maternal age was 31 years, the average disease duration 5 years.Mean BASDAI was 3.0 before conception, 3.4, 3.4 and 3.5 in the 1st, 2nd and 3rd trimester, and 3.4 within 6 months postpartum. The figure shows mean values of the BASDAI and its individual components in the different time periods. Fatigue was higher than the mean score during all phases, and especially elevated in the 1st and 3rd trimester. Furthermore, values for neck, back or hip pain were higher than the mean score, especially from 2nd trimester on. All other components were lower than the mean score.Data were not reported for all pregnancies and all time periods. Availability was highest in the 2nd and 3rd trimester with reported BASDAI in 60% and 62% of the pregnancies, respectively. Lowest reporting was 24% in the preconception period because only a part of the women was also observed before pregnancy.ConclusionThe BASDAI is a validated instrument for assessing disease activity in patients with axSpA. Since the calculation of the score also includes factors that can be influenced by pregnancy, it may only be of limited value for measuring disease activity in pregnancy. This analysis shows that mainly fatigue and back pain in particular have an impact on the mean BASDAI. A limitation of this analysis is that data were not available for all measured time points of the individual pregnancies. Therefore, the results should be confirmed by other studies.Figure 1.Means of BASDAI components before, during and after pregnancy (the table presents means ± standard deviation).AcknowledgementsThis work was supported by a research grant from FOREUM Foundation for Research in Rheumatology.Disclosure of InterestsYvette Meissner Speakers bureau: Pfizer, Anna Moltó Consultant of: UCB and BioGen, Grant/research support from: UCB, Nathalie Costedoat-Chalumeau Grant/research support from: to my institution (UCB), Rebecca Fischer-Betz: None declared, Frauke Förger Speakers bureau: UCB pharma, GSK, Consultant of: UCB pharma, GSK, Roche, Grant/research support from: UCB pharma, GSK, Marianne Wallenius: None declared, Anja Strangfeld Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, Pfizer, Roche, Sanofi, UCB.

BackgroundMixed connective tissue disease (MCTD) is a systemic auto-immune disorder, being probably the least common among the connective tissue diseases. Symptoms can be severe and could affect health-related quality of life (HRQoL). Identification of the burden of MCTD patients is of key importance to provide appropriate pharmacological and non-pharmacological care. No reports on HRQoL have been published in adult patients with MCTD.ObjectivesTo perform an explorative study to evaluate HRQoL and its main determinants in MCTD patients, and compare HRQoL between MCTD and matched systemic sclerosis (SSc) patients.MethodsMCTD patients fulfilling the Kahn criteria and participating in the MCTD prospective follow-up cohort of the Leiden University Medical Center were included. In addition, SSc patients matched for age, gender and disease duration were included for comparison. Data on disease characteristics, functional disability and HRQoL were collected annually for both disease groups. HRQoL was evaluated using the 36-Item Short Form Health Survey (SF36) and EuroQol (EQ5D). At baseline, HRQoL, as reflected by SF36 mental component score (MCS), SF 36 physical component score (PCS) and EQ5D were compared between MCTD and SSc patients. For MCTD patients, factors associated with HRQoL at baseline were identified using linear regression and change in HRQoL over 3 years was evaluated using linear mixed models. In addition, characteristics of MCTD patients who showed worsening of MCS and/or had PCS superior to the minimal clinical important difference of three points were identified.ResultsThirty-four MCTD patients (121 visits; 82% female, mean age 42 years, median disease duration 45 months) and 102 SSc patients (424 visits; 82% female, mean age 45 years, median disease duration 49 months) were included. At baseline, MCTD-patients more often had ILD (47% vs. 34%, p=0.027), cardiac involvement (30% vs. 2%, pBaseline HRQoL in MCTD was comparable to HRQoL in SSc, with mean SF36-PCS of 40.2 (SD:9.1) and mean SF36-MCS of 44.9 (SD:9.9), which is (nearly) one standard deviation lower than the general Dutch population. The SF36 subscore “general health perception” was the most impacted in both groups (MCTD: 38.5 [SD:7.0], SSc: 39.9 [SD:8.9]). The median EQ5DNL was 0.38 (IQR:0.14 – 0.54) and comparable between SSc and MCTD.At baseline, in MCTD, ILD was significantly associated with SF36-PCS (β:6.98, 95% CI: 1.10 to 12.86) and SF36-MCS (β:-8.10, 95% CI:-14.93 to -1.26). Sclerodactyly was significantly associated with EQ5DNL (β:0.006; 95% CI:0.002 to 0.010) and SF36-PCS (β:0.12, 95% CI:0.03 to 0.21). No other significant associations were identified.Over time, in MCTD, both the SF36-MCS and SF36-PCS improved significantly (MCS: β:2.35/year [95% CI:0.58 to 4.13], PCS: β:1.34/year [95% CI:0.03 to 2.65), whereas EQ5DNL was stable. Explorative analyses did not reveal a specific clinical characteristic with significant impact on the change of HRQoL over time. With an MCID of 3 points on the MCS and PCS, 7 MCTD-patients worsened on the MCS and 3 on the PCS. Patients who showed worsening of MCS over time tended to be older, more often had ILD, sclerodactyly and GI complaints, and had worse exercise tolerance. All these differences did not reach statistical significance. The patients who decreased PCS more often had ILD (100% vs. 41%, p=0.015), and used glucocorticoids more often (33% vs. 0%, p=0.046), were slightly older and had a worse exercise tolerance as compared to those who showed a stable/improving PCS over time.ConclusionLike in SSc, HRQoL is significantly impaired in MCTD, especially the general health perception of patients. Cardiac involvement, ILD, age and worse functional disability might specifically impact HRQoL in MCTD. However, these associations need further evaluations in larger cohorts.Disclosure of InterestsNone declared

BackgroundPatients with Systemic Lupus Erythematosus (SLE) experience both physical and psychosocial restrictions that negatively impact their quality of life. Coping mechanisms have turned out to be important contributors to health-related outcomes, not only in SLE but also other chronic conditions. However, there is limited understanding of factors that enhance or hamper coping in SLE.ObjectivesTo analyse parameters associated with longitudinal changes in coping behaviour in patients with SLE who take part in a long-term SLE patient cohort study.MethodsSince 2001, the German nationwide SLE patient longitudinal (Lupus Langzeit ‘LuLa’) study annually administers self-reported questionnaires to SLE patients.In addition to demographic and the annually probed extended clinical data (e.g., medication, disease activity, fatigue, depression), in both 2009 and 2014 we assessed the Pain-related Self Statements Scale (PRSS) to perceive information related to coping behaviour. This includes ‘positive coping’ as well as catastrophizing as a dysfunctional form of coping behaviour.Statistical analysis was accomplished by a linear regression model adjusting for age, pain, number of comorbidities and net income. The PRSS score difference from 2009 and 2014 was used as the dependent variable. Factors from the i) medical (involvement of the skin, pain, fatigue), ii) activity (basic, leisure, sports), iii) intrinsic (depression, kinesiophobia, perceived health control), and iv) social participation categories were entered as independent variables.Results272 patients (96.7% female) provided valid PRSS questionnaires in both 2009 and 2014. In 2009 the mean age in this cohort was 51 years (SD 11.2) with an average disease duration of 16.2 years (SD 8.3). The mean reported lupus activity (VAS 0-10) during the last three months was 3.7 (SD 2.4). During the six-year observation period, the proportion of improvement (46.2%) and deterioration (47.4%) in coping score was almost balanced, while in catastrophizing score more participants improved (50.0%) than deteriorated (37.0%).A perceived high internal control, thus the belief that health outcomes are contingent on personal behaviour, was associated with an improvement in the coping score [HLC, b=0.061 (95%-CI 0.014; 0.109), p=0.012]. Conversely, high external control convictions, e.g., the belief that doctors and other third parties determine health outcomes, were associated with a worse coping score [HLC, b=-0.090 (95%-CI -0.154; -0.026), p=0.006]. Deterioration in depression [ADS-L, b=0.015, (95%-CI 0.006; 0.025), p=0.002] and impaired social participation [IMET, b=0.043, (95%-CI 0.000; 0.085), p=0.050] were associated with a deterioration of catastrophizing, whereas better internal control [HLC, b=-0.046, (95%-CI -0.080; -0.012), p=0.009] was associated with its improvement.Mucocutaneous involvement, fatigue and the extent of physical activity were not significantly associated with either coping or catastrophizing scores in the regression analysis.ConclusionIn line with data from other chronic diseases, our findings in a longitudinal SLE cohort emphasise the role of intrinsic factors, such as mental health status and self-efficacy, improving the quality of life in SLE patients via successful coping behaviour. Affirmative action measures and programs to improve social participation may yield additional benefits.AcknowledgementsThe LuLa study is supported by unrestricted grants from GlaxoSmithKline, UCB Pharma and AstraZeneca.Disclosure of InterestsEmily Reutemann: None declared, Ralph Brinks: None declared, Jutta G. 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, Martin Aringer: None declared, Matthias Schneider Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Gamal Chehab Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study.

Schwangerschaften bei Patientinnen mit rheumatischen Erkrankungen stellen eine besondere Herausforderung fur den behandelnden Arzt dar. Dies beginnt bei einer kompetenten Beratung der oft besorgten Patientin vor Konzeption und mundet in eine engmaschige Begleitung wahrend und nach der Graviditat. Inzwischen sind immer mehr Risikofaktoren fur ungunstige Schwangerschaftsverlaufe identifiziert, die teils kontrollierbar oder gar iatrogen bedingt sind und folglich bedacht werden sollten. Ein weiterer Grundstein in der Behandlung dieser Patientengruppe ist die Auswahl von und Aufklarung zu geeigneten Medikamenten wahrend Schwangerschaft und Stillzeit. Hierzu liefern Studien und aktuelle Empfehlungen wertvolle Hilfestellungen. Gelingt eine konsequente Krankheitskontrolle unter schwangerschaftskompatibler Medikation, konnen betroffene Frauen in vielen Fallen einen erfolgreichen Schwangerschaftsausgang erleben.

Improvement of health-related quality of life (HRQoL) is a prioritized treatment target in systemic lupus erythematosus (SLE). A retrospective chart review of patients with repeated HRQoL measurements from the outpatient department was conducted in order to better understand which factors drive HRQoL in established SLE. Of particular interest was the association between HRQoL and disease activity.The medical outcomes study short form 36 (SF-36), systemic lupus activity measure (SLAM) and routine clinical data of 169 patients (83% female, mean age 40.3 ± 13 years, disease duration 9.4 ± 7 years) over an average of 7.1 ± 4.2 years were available for analysis by linear mixed modelling. Factors associated with the physical component summary (PCS) and mental component summary (MCS) of the SF-36 were assessed. The proportion of HRQoL which could be explained by the variables was estimated by marginal RAt baseline, SLE patients showed a reduced HRQoL in all subscales of the SF-36 including PCS and MCS with the exception of vitality. A higher PCS over time was significantly associated with concurrent parameters, such as intake of antimalarial drugs, no glucocorticoid use, less fatigue, lower disease activity as well as to the baseline parameters of younger age and higher PCS (mRThe use of antimalarial drugs and no glucocorticoid intake as well as low current disease activity are modifiable factors associated with a better physical HRQoL. The mental component of HRQoL was poorly represented by conventional parameters and not associated with parameters of disease activity in the present study cohort.

As long as we cannot cure diseases such as systemic lupus erythematosus (SLE), it must be our goal that people with SLE can live a largely normal life. It should not be dominated by the disease. The main goal is secondary prevention, i. e. the prevention of harm. In 2020 we want to make a better contribution to this aim. For this article on SLE, being fit for 2020 therefore means applying the basic concepts of care for patients with SLE on a regular basis. The focus is on the new concepts resulting from the new classification criteria, the optimized basic care (BASIC), the complex communication with those affected, the new EULAR recommendations for monitoring SLE, the integration of biologics into the treatment regimen, the targeted therapy (T-2-T) and thus the criteria low disease activity and remission, the question of new care structures for rare and complex systemic diseases and finally the outlook on future treatment concepts, the basis of which we will all create in the coming years. If we consistently apply the current options, we will be able to further improve the life situation and quality of life of those affected even without newly approved drugs.

Supplemental Material for Successful conception in a 34-year-old lupus patient following spontaneous pregnancy after autotransplantation of cryopreserved ovarian tissue by G Chehab, J Krüssel, T Fehm, R Fischer-Betz, M Schneider, A Germeyer, MB Suerdieck, V Kreuzer and J Liebenthron in Lupus

Young patients and adolescents with chronic rheumatic diseases have the same desires, fears and needs in terms of sexuality and pregnancy as their healthy peers. In most cases adolescents are already sexually active before transition from pediatric to adult rheumatological care takes place. Pregnancies in women with rheumatic diseases are associated with increased maternal and fetal risks, especially when they occur unplanned in the course of active disease or under teratogenic drugs. Safe contraception is therefore crucial in preventing unwanted pregnancies. The choice of contraception should anticipate the safety of the method of contraception as well as age-dependent practicability. A strategy of "double protection" through the use of condoms for contraception and prevention of sexually transmitted diseases combined with another safe contraception method should be recommended. Women with rheumatic diseases are more susceptible to acquire persisting human papilloma virus (HPV) infections and the subsequent progression to cervical cancer. In women with rheumatic diseases HPV vaccination induces high seroconversion rates, is safe and does not seem to induce disease activity. The care of adolescent women with rheumatic diseases before, during and after medical transition needs to encompass an open, early and continuous counselling regarding these topics in order to retain the individual health-related quality of life and to adapt this care to age-specific needs.

The German Registry of Autoimmune Diseases 2 (GRAID2) is a retrospective, non-interventional, multicenter registry study collecting data from patients with inflammatory, mainly rheumatic diseases refractory to standard of care therapy and treated with an off-label biologic therapy. The retrospective documentation comprised case history, diagnosis, course of disease (including safety and global efficacy). The objective was to evaluate the global clinical outcome and safety of off-label biologic therapy in clinical practice.Data from 311 patients with an overall observation period of 338.5 patient-years were collected. The mean patients age was 47.8 years with 56.9% females. The most frequently documented diagnoses comprised rejection prophylaxis/therapy after renal transplantation (NTX, 18.3%), ANCA-vasculitides (17.4%), systemic lupus erythematosus (SLE, 10.3%), autoinflammatory fever syndromes (8.4%), autoimmune myositis (7.4%) and pemphigus (5.8%). Documented biologic therapies included rituximab (RTX, 70.1%), tocilizumab (TCZ, 9.3%), infliximab (IFX, 7.1%), anakinra (ANK, 5.5%), adalimumab (ADA, 3.5%), etanercept (ETA, 2.3%) and certolizumab (CTZ, 0.6%). After initiation of off-label biologic treatment, tolerability was assessed by the physicians as "very good"/"good" in 95.5%. Altogether, 275 adverse events were documented and of these, 104 were classified as serious adverse events and occurred in 62 patients. In 19 of these patients severe infections (30.6%) were documented, resulting in a rate of 5.6 severe infections per 100 patient years. A total of six deaths were documented, while five of these cases were rated as not related to the biologics treatment. Notably, the use of RTX in patients with small vessel vasculitides and of TCZ in patients with large vessel vasculitides prior to their approval support their relevance in clinical management of patients with severe diseases.The results of this registry together with data of GRAID1 provide evidence that use of off-label biologic therapies in patients with inflammatory rheumatic diseases refractory to conventional treatment did not result in any new safety signal already known for these compounds or subsequently shown by clinical trials in certain entities.

Kinderwunsch und Schwangerschaften bei entzundlich rheumatischen Erkrankungen stellen eine besondere Herausforderung in der Arzt-Patienten-Beziehung dar und erfordern eine optimale gemeinsame Strategie. Die meisten betroffenen Frauen konnen eine erfolgreiche Schwangerschaft erleben, und die uberwiegende Zahl der Kinder kommt gesund zur Welt. Die Planung einer Schwangerschaft in einer moglichst inaktiven Erkrankungsphase und eine regelmasige Uberwachung sind von entscheidender Bedeutung. Dabei sind die sorgfaltige Einschatzung von moglichen Risiken und die Aufklarung uber den Einsatz von antirheumatischen Therapien vor, wahrend und nach einer Graviditat ein wichtiger Bestandteil.

Similar to patients with other rheumatic diseases, patients with systemic lupus erythematosus (SLE) nowadays can also have the desire to terminate immunosuppressive and immunomodulatory medications. In order to provide appropriate advice to patients, the two main issues are the risk of severe adverse events under long-term therapy with any drug and the perceived risk of a flare, in particular of severe flares. The risks of long-term therapy vary greatly between drugs, ranging from severe unacceptable risks with cyclophosphamide and higher dose glucocorticoids to low risks usually outweighed by long-term benefits with hydroxychloroquine. The individual risk of flares is often difficult to estimate but clinical remission and at least 3 years of immunosuppression are recommended for lupus nephritis. The duration of remission can also be shorter in cases of milder forms of disease. This review article tries to put the available evidence into a clinical perspective and to derive concrete recommendations.

Viele Lupus-Patientinnen befinden sich im gebarfahigen Alter, und Kinderwunsch und Schwangerschaft sind fur sie daher ein wichtiges Thema. Die gute Nachricht ist, dass die meisten Betroffenen eine erfolgreiche Schwangerschaft haben konnen und die uberwiegende Zahl der Kinder gesund zur Welt kommt. Dennoch gibt es Besonderheiten zu beachten. So kommt es bei Frauen mit Lupus in einer Schwangerschaft durchschnittlich zu mehr Lupus-Schuben als auserhalb der Schwangerschaft. Zudem haben Frauen mit Lupus haufiger geburtshilfliche Probleme wie zum Beispiel Fehlgeburten oder Fruhgeburten. Diese Probleme treten vor allem bei Frauen auf, die schwanger werden, wenn ihr Lupus aktiv ist, bei Frauen mit einer Nierenbeteiligung, Frauen mit einem Antiphospholipidsyndrom und wenn Antimalariamittel abgesetzt werden. Durch Planung einer Schwangerschaft lasst sich dieses Risiko deutlich verringern! Ganz wichtig ist es daher, einen Kinderwunsch fruhzeitig mit dem behandelnden Rheumatologen zu besprechen und eine Schwangerschaft bei stabiler Erkrankung und angepasster Therapie optimal zu planen

In a joint initiative by the boards of the German Society for Rheumatology (DGRh) and the Association of Rheumatology Clinics (VRA) the European "standards of care" for rheumatoid arthritis, recently suggested by the European Musculoskeletal Conditions Surveillance and Information Network (eumusc.net) and supported by the European League Against Rheumatism (EULAR), were translated and annotated. The recommendations include aspects of the management of the disease, actual medical care, and access to information - this includes all types of support people with RA need, and, last but not least communication of the necessary knowledge. Furthermore, health care structures such as the availability of medical staff with relevant expertise are also important.

Die Behandlungsmoglichkeiten entzundlich-rheumatischer Erkrankungen wie der rheumatoiden Arthritis, Spondylitis ankylosans und des systemischen Lupus erythematodes verbessern sich stetig. Dies fuhrt auch dazu, dass sich eine wachsende Zahl der oft jungen Patientinnen ihren Kinderwunsch erfullen mochte. Das zunehmende Verstandnis der Erkrankungsverlaufe in der Schwangerschaft bzw. postpartal erlaubt eine optimierte Beratung der betroffenen Frauen vor Konzeption. Von entscheidender Bedeutung sind die Planung einer Schwangerschaft in einer moglichst inaktiven Erkrankungsphase und eine regelmasige Uberwachung. Dabei sind die sorgfaltige Einschatzung moglicher Risiken und die Aufklarung uber den Einsatz von antirheumatischen Therapien vor, wahrend und nach einer Graviditat wichtige Bestandteile.

ZusammenfassungDer systemische Lupus erythematodes (SLE) ist eine komplexe Autoimmunerkrankung und betrifft vor allem Frauen im reproduktiven Alter. Eine Konsequenz daraus ist die häufige Interaktion mit Kinderwunsch und Schwangerschaft. Der Ausgang von Schwangerschaften bei SLE hat sich in den vergangenen Jahrzehnten unzweifelhaft verbessert, mit einem deutlichen Anstieg der Anzahl an Lebendgeburten. Dennoch kann eine Schwangerschaft für Lupus-Patientinnen mit erheblichen mütterlichen und kindlichen Risiken verbunden sein. Eine adäquate Betreuung in der Schwangerschaft umfasst eine gynäkologisch-rheumatologische Zusammenarbeit, ein abgesprochenes und definiertes Management sowie eine erfahrene Neonatologie. Jede SLE-Schwangerschaft sollte im Rahmen eines präkonzeptionellen Gesprächs geplant werden, um das individuelle Risiko einzuschätzen.

Inflammatory rheumatic diseases often affect females of childbearing age and pregnancy remains a challenge for this group of patients and their physicians. However, the majority of patients can now have successful pregnancies and deliver healthy babies as a result of our improved knowledge of the risks encountered during pregnancy, better preventive and therapeutic measures, and in particular close rheumatological, obstetric and neonatal monitoring. To ensure a favorable outcome, pregnancy should be planned to take place during a period of disease stability, monitored closely (physical examination, laboratory tests, and Doppler ultrasound), and treated appropriately.

Early diagnosis of systemic lupus erythematosus (SLE) is a challenge even for experienced rheumatologists due to the heterogeneous appearance of the disease. The initial phase of SLE often comprises unspecific general symptoms and only few characteristic clinical and laboratory abnormalities in the early course. Seriously affected patients meet the classification criteria in early stages but many other affected patients do not. A concentration only on young women as possible new cases means that more than 50 % of all persons affected will not be identified. Therapy is mainly guided by the type and severity of symptoms. Organ manifestations need to be examined at each presentation because there is a high possibility for modification in the course of the disease especially in the early stages. Early intervention should prevent increasing damage. Key elements of medical treatment are antimalarial agents. Furthermore, control of co-morbidities and optimization of lifestyle are crucial.

Pregnancy in women with rheumatic diseases represents a challenge for patients and physicians and requires optimal shared decision-making strategies. However, the majority of women can have a successful pregnancy and the vast majority of babies are born healthy. Specific preconception care should be offered to women with rheumatic diseases to optimize and increase the chances of a successful pregnancy. A careful assessment of possible risks and the justified use of antirheumatic drugs before, during and after pregnancy are key issues.

Mycophenolate mofetil (MMF) is among the few immunosuppressive drugs with sufficient data from controlled studies on the therapy of systemic lupus erythematosus (SLE). In the light of results from recently published randomized controlled trials on the effectiveness of MMF in the treatment of lupus nephritis, it has become necessary to revise the statement of the Germany Society of Rheumatology on the use of MMF for SLE. In the induction therapy of lupus nephritis MMF has been shown to be equivalent in effectiveness to i.v. cyclophosphamide and superior to azathioprine in the maintenance phase. Cyclophosphamide is inferior to MMF and probably also to azathioprine as maintenance therapy and should therefore, not be considered for this purpose and also because of its toxicity. For other organ manifestations MMF also constitutes an alternative when approved immunosuppressants are not able to control the disease and glucocorticoids cannot be reduced to 7.5 mg prednisolone daily equivalents or less.

The central role of B-lymphocytes in the pathogenesis of systemic lupus erythematosus (SLE) has turned the attention particularly to more specific B-cell targeted therapies in recent years. Belimumab is a monoclonal antibody against the B-lymphocyte stimulator BlyS and was approved in 2011 as additional therapy for adult patients with SLE. Based upon the available data, treatment with belimumab is recommended in patients with clinically and serologically active SLE despite individually adjusted standard therapy. The standard therapy usually consists of antimalarial agents, an immunosuppressive drug (e.g. azathioprine) and/or steroids. Even the necessity for regular higher dosages of ≥ 7.5 mg prednisolone equivalents/day could be a feasible medical indication for belimumab. Due to lacking data the use of belimumab is not recommended for the purpose of treating severe active SLE with renal or central nervous system involvement until efficacy has been shown for these indications.

The treatment of inflammatory rheumatic diseases, such as rheumatoid arthritis, spondylitis ankylosans and systemic lupus erythematosus, is improving continuously. This has lead to an increasing number of young patients with a wish to have children. Greater insight into the course of rheumatic diseases during pregnancy and post partum has enabled optimized support for women with rheumatic diseases wishing to have children. To ensure a favorable outcome, pregnancy should be started during a period of disease stability and should be monitored closely. A careful assessment of possible risks and the justified use of antirheumatic drugs before, during and after pregnancy are key issues for success.

To analyse if defensins, immunomodulatory peptides involved in angiogenesis and elevated in the sera of systemic lupus erythematosus (SLE) patients, relate to cardiovascular disease in SLE.Serum levels of the defensins human beta defensin 2 (hBD2) and human neutrophil peptide (HNP) of 72 SLE patients were determined by ELISA at baseline. Cardiovascular risk factors and the occurrence of cardiovascular events (CVE: stroke, claudication, angina pectoris, myocardial infarction) were recorded over 6 years. Intima media thickness of the carotid arteries (CIMT) was measured by ultrasound in 42 patients at baseline and at 4 years. Normally distributed log-transformed defensin levels (log-hBD2 and log-HNP) were used for statistical analysis.SLE patients who experienced a CVE had significantly higher log-hBD2 values and a likelihood-ratio for CVE of 2.23 when levels increased above 3.3 log(ng/ml). Using binary logistic regression analysis, log-hBD2 significantly contributed to a model also incorporating the number of traditional cardiovascular risk factors (dyslipidemia, hypertension, positive family history, age, smoking) as explanatory variables for the incidence of cardiovascular events. Moreover, SLE patients with progressive CIMT showed increased log-hBD2 and log-HNP values. Both defensin-levels also showed some correlation to the plaque stadium at baseline (hBD2: r2 0.10; HNP r2 0.12). Neither log-hBD2 nor log-HNP were correlated to traditional cardiovascular risk factors.HNP and especially hBD2 may be indicators of progressive cardiovascular disease in SLE.

Cardiovascular diseases are the main cause of death worldwide and dyslipidemia constitutes a substantial risk factor. Patients with rheumatic diseases, especially active inflammatory arthritis and systemic lupus erythematosus, show unfavorable lipid profiles, which, however, do not account for the total excess cardiovascular morbidity. Effective disease management, life-style changes and cholesterol-lowering agents can ameliorate the lipid profile and lower cardiovascular mortality. Due to their anti-inflammatory and potent cholesterol-lowering properties, statins are the pharmacological agents of first choice. National and international guidelines on cardiovascular risk prevention differ concerning appraisal of the individual risk and lipid targets. The EULAR recently released recommendations for cardiovascular risk management in patients with inflammatory arthritis.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with increased mortality, largely as a consequence of cardiovascular (CV) disease. Studies found relative risk ratios of 2 for myocardial infarction in RA and up to 7 for myocardial infarction in SLE patients.Beyond the traditional CV risk factors, chronic systemic inflammation has been shown to be a crucial factor in atherosclerosis development and progression from endothelial dysfunction to plaque rupture and thrombosis. Numerous studies have shown that atherosclerosis is not a passive process characterized by accumulation of lipids in the vessel walls, but rather represents active inflammation of the vasculature. Inflammatory cells such as macrophages, monocytes and T cells play an important role in the development of both RA and atherosclerosis.According to the recently published EULAR recommendations for CV risk screening and management in patients with inflammatory arthritis, annual CV risk assessment is recommended for all patients with RA. Any CV risk factors identified should be optimally managed. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower CV risk.

Inflammatory rheumatic diseases often affect females of childbearing age and pregnancy remains a challenge for this group of patients and their physicians. However, the majority of patients can now have successful pregnancies and deliver healthy babies as a result of our improved knowledge of the risks encountered during pregnancy, better preventive and therapeutic measures, and in particular close rheumatological, obstetric and neonatal monitoring. To ensure a favorable outcome, pregnancy should be planned to take place during a period of disease stability, monitored closely (physical examination, laboratory tests, and Doppler ultrasound), and treated appropriately.

In contrast to many other medications, chloroquine and hydroxychloroquine are approved treatment options for systemic lupus erythematosus (SLE). Antimalarials reduce the frequency of disease flares and contribute to the maintenance of remission. Apart from its direct effects on SLE activity, antimalarials seem to protect against thrombotic events and have a beneficial effect on glucose and lipid profiles, which might help reduce the high cardiovascular risk of SLE. Hydroxychloroquine is the only treatment shown to be effective in reducing the risk of damage accrual in SLE patients. Finally, antimalarials are inexpensive, especially compared with more recent treatments, and are well tolerated in SLE. Despite all these benefits, still only about 40%-50% of SLE patients are treated with (hydroxy)chloroquine. Particularly in early disease phases, antimalarials should be considered for every lupus patient, assuming there are no contraindications.

Even though no new treatment for systemic lupus erythematosus (SLE) has been approved in over 40 years, the treatment possibilities have expanded decisively in this time. The available evidence for most forms of therapy is rather thin, yet there is a wide consensus on an individual immunosuppressive therapy that is adjusted to the illness activity and severity. Various new substances, e.g. other immunosuppressants and anti-cell therapies have been tested, mostly in open studies. Considering the experience in other indications, mycophenolate mofetil and rituximab have a very promising potential to be approved for therapy of SLE. Aside from these, "old medications" such as antimalarial drugs still possess a high value. Besides the effective suppression of the illness activity, this is especially decisive for the improvement of the long-term prognosis, the treatment of co-morbidities and secondary prevention and the avoidance of negative effects of the illness and therapy, such as infections, osteoporosis, and premature arteriosclerosis. As these "simple" measures often remain disregarded in modern therapy, they will be focused on in this overview on the current treatment concepts for SLE and these aspects will be discussed in greater depth. With regard to new future therapies, we refer the reader to other current publications.

We present nine cases of systemic lupus erythematosus with refractory disease that we treated with the chimeric monoclonal anti-CD20 antibody rituximab. Three patients had renal disease, three neurological involvement with transverse myelitis and vasculitis of the central nervous system, one thrombocytopenia, one skin involvement with generalized erythema and one patient had constitutional, haematological and immunological symptoms. Two patients with renal disease, the patient with immune thrombocytopenia and the three patients with neurological disease, who stayed in remission despite a reduction of immunosuppressive therapy, responded particularly well to the therapy. Five of nine patients showed an improvement in ECLAM of at least two points. During therapy only minor adverse events were observed. One patient died during follow-up which was unrelated to the therapy. The selective depletion of B-lymphocytes in the therapy of systemic lupus erythematosus seems to be an effective and safe treatment option for different manifestations.

According to the NIH scheme, the "evidence based medicine" standard in the treatment of severe proliferative lupus-nephritis is cyclophosphamide in combination with steroids. Undesired effects, therapy resistance, and deficient long-term effects underscore the necessity for the development of alternative therapies for the treatment of organ involvement. Mycophenolate mofetil (MMF) possesses the potential to decisively improve the therapeutic possibilities for systemic lupus erythematosus (SLE). On the basis of the available data, MMF represents an alternative to the current standard therapies for severe lupus-nephritises and shows less toxicity. MMF is also effective in patients with other manifestations refractory to conventional therapy. Questions remain unanswered on the optimal dosage and possible reduction in cases of remission. In addition, the duration of maintenance therapy is unclear. Therefore, large, prospective, randomized clinical studies in the treatment of lupus-nephritis with a sufficiently long follow-up phase are underway.

Morbidity and co-morbidities in patients with lupus erythematosus (LE) result in an impairment, limiting activities of daily living. We compared the handicap, appraised by the German welfare system in patients with LE and their diagnosis, morbidities and co-morbidities, therapy, functional capacity, psychological status and general health. The data were obtained in an anonymous self-administered questionnaire conducted by the lupus patient association. 892 data sets were available for the trial. The mean age was 46.9y, disease duration was 10.3y. The patients had 3.8 concomitant diseases on average. 39.7% were still working and 35.4% drew a pension. 59.2% made an application for disability, which wasn't assigned in only 2.5% of cases. 82.6% had an average grade of disability of more than 50%. It demonstrated a good correlation to age, disease duration, type of LE and therapy. Predictors for a worse assessment were disease duration, osteoarthritis, cerebral insults and functional capacity. In conclusion the data demonstrate a fair appraisal of disability by the German welfare system in patients with LE. Self-administered questionaires can yield credible results.

Large increases in mortality related to premature atherosclerosis with coronary artery disease and stroke have been reported during the last few years in patients with systemic lupus erythematosus (SLE). Studies found relative risks of 5 to 7 for myocardial infarction in SLE patients. The traditional risk factors fail to fully account for accelerated atherosclerosis in SLE and APS, in addition prolonged glucocorticoid therapy and long duration of SLE seem to be of importance. The disease SLE per se is an independent risk factor. The current pathogenic hypothesis for atherosclerosis involves an inflammatory response, autoantibodies, immune complexes (containing antibodies to phospholipids, to oxidized LDLs, and to endothelial cells), CD40/CD40 ligand interactions, and bacterial or viral infections responsible for an immune response. The determination of classic and new risk factors, together with specific autoantibody titers and the use of Doppler carotid ultrasound, are useful methods to detect early atherosclerosis. Therapeutic strategies, including early risk factor intervention and effective control of inflammation, are essential to reduce morbidity and mortality and should be incorporated into the management of connective tissue disease with the goal of protecting patients against atherosclerosis.

During the last few decades, the prognosis for patients with systemic lupus erythematosus (LE) has changed from high early mortality to a more chronic longterm course. Although the prevalence of LE has been estimated at 20-50/100,000, data concerning the situation of LE patients in Germany are sparse. Since 2001, a documentation within the German Lupus Self-Help Organisation scheduled for a period of 10 years (LULA) has been recording at the patient level the actual status and the long-term course of a large group of LE patients. A questionnaire adapted from the German rheumatological database is updated once a year and sent to all members.In 2001, 1033 members participated in the documentation. Of these, 92.2% were women (mean age 45.8 years) with a mean disease duration of 9.9 years. 37.6% were employed, and 24.5% were on early retirement. 50.2% rated their overall health status as "not so good" or "poor". Most were receiving treatment with [hydroxy-]chloroquine (35.2%) or azathioprine (21.9%), while 67.9% were receiving corticosteroids. The most frequent comorbidities reported were hypertension (33%), scarring skin disease (24.4%), osteoarthritis (25.2%), osteoporosis (24%), psychiatric disorders/depression (22.9%) and chronic renal disease (22%). Thromboembolic events were reported in 18.5%, myocardial infarction in 2.3% and stroke in 4.8% of cases. Concerning their main contact person for health care, 63.6% specified the rheumatologist. In comparison with other cohort studies and in particular with the German rheumatological database, the data provided exclusively by patients are feasible. Concerning the severity of their disease, their treatment and their global assessment of health status, LULA participants are comparable with other LE patients and can be seen as representative of LE patients in Germany. Further assessment especially of long-term data are needed to obtain additional insights into the burden of the disease and the need for special medical care.

Guidelines for assessments of connective tissue diseases in social jurisdiction and for insurance are not available in Germany. This article is a guideline reflecting published data, modern therapy and actual prognosis. In addition, help for interpretation and examples are given.