Publications by authors named "Andreas Schwarting"

88 Publications

Effect of nurse-led care on outcomes in patients with ACPA/RF-positive rheumatoid arthritis with active disease undergoing treat-to-target: a multicentre randomised controlled trial.

RMD Open 2021 04;7(1)

Rheumatologie and Immunologie, Medizinische Hochschule Hannover, Hannover, Germany

Objective: To determine the non-inferiority of nurse-led care (NLC) in patients with anticitrullinated protein antibody (ACPA)-positive and/or rheumatoid factor (RF)-positive rheumatoid arthritis (RA) with active disease who are starting disease-modifying antirheumatic drug therapy, following treat-to-target (T2T) recommendations.

Methods: A multicentre, pragmatic randomised controlled trial was conducted to assess clinical effectiveness, anxiety, depression and patient satisfaction following a non-inferiority design. The participants were 224 adults with ACPA/RF-positive RA who were randomly assigned to either NLC or rheumatologist-led care (RLC). The primary outcome was the Disease Activity Score in 28 Joints measured with C reactive protein (DAS28-CRP) assessed at baseline and after 3, 6, 9 and 12 months. A DAS28-CRP difference of 0.6 was set as the non-inferiority margin. Mean differences between the groups were assessed following per-protocol and intention-to-treat strategies.

Results: Demographic data and baseline characteristics of patients in the NLC group (n=111) were comparable to those of patients in the RLC group (n=113). The improvement in disease activity (change in DAS28-CRP, primary outcome) over the course of 12 months was significant in both groups (p<0.001). No significant differences were observed between the NLC and RLC groups (p=0.317). Non-inferiority of NLC was shown for the primary outcome and all secondary outcomes.

Conclusion: This study supported the non-inferiority of NLC in managing T2T and follow-up care of patients with RA with moderate to high disease activity and poor prognostic factors in addition to RLC.

Trial Registration Number: DRKS00013055.
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http://dx.doi.org/10.1136/rmdopen-2021-001627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055148PMC
April 2021

Development and validation of rheumatoid arthritis disease activity indices including HandScan (optical spectral transmission) scores.

Arthritis Care Res (Hoboken) 2021 Mar 26. Epub 2021 Mar 26.

Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Objectives: To develop and validate a composite RA disease activity index using optical spectral transmission (OST)-scores obtained with the HandScan replacing tender and swollen joint counts.

Methods: RA patients from a single centre routinely undergoing HandScan measurements and at least one concurrent OST-score and DAS28 were included. Data was extracted from medical records. Linear regression analyses with DAS28 as outcome were performed to create a disease activity index (DAS-OST). OST-score, ESR and patient global assessment (PGA-)VAS, gender, age, disease duration and RF-status were evaluated as independent variables. Final models were derived, based on statistical significance of coefficients and model fit. Of the data, 2/3 was used for development and 1/3 for validation; external validation was performed in a cohort from another centre. Agreement between DAS-OST and DAS28 was assessed using the Bland-Altman plot method and intra-class correlation coefficient (ICC). Diagnostic value of DAS-OST was determined for established definitions of remission, and low (L), and high (H) disease activity (DA).

Results: Data of 3358 observations from 1505 unique RA patients were extracted. DAS-OST was defined as: -0.44 + OST*0.03 + male*-0.11 + LN(ESR)*0.77 + PGA-VAS*0.03. The ICC between DAS-OST and DAS28 were 0.88 (95%CI 0.87-0.90) and 0.82 (95%CI 0.75-0.86) and measurement errors 0.58 and 0.87 in internal and external validation, respectively. Sensitivity for remission, LDA and HDA were 79%, 91%, 43%, and specificity 92%, 80%, 96% in external validation.

Conclusion: Using the HandScan, RA disease activity can be accurately estimated if combined with ESR, PGA-VAS and gender into a disease activity index (DAS-OST).
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http://dx.doi.org/10.1002/acr.24607DOI Listing
March 2021

The relationship between BAFF serum levels, anti-NMDAR autoantibodies and fatigue in patients with systemic lupus erythematosus and multiple sclerosis.

Autoimmun Rev 2021 May 14;20(5):102802. Epub 2021 Mar 14.

Division of Rheumatology and Clinical Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Acura Rheumatology Center Rhineland Palatinate, Bad Kreuznach, Germany; University Center of Autoimmunity, Johannes Gutenberg-University, Mainz, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2021.102802DOI Listing
May 2021

Dr. Triantafyllias, reply.

J Rheumatol 2021 Mar 15. Epub 2021 Mar 15.

ACURA Rheumatology Center Rhineland-Palatinate, Bad Kreuznach; Internal Medicine I, Department of Rheumatology and Clinical Immunology, Johannes Gutenberg University Medical Center, Mainz; Internal Medicine I, Department of Gastroenterology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. The authors declare no financial support or other benefits from commercial sources for the work reported in the correspondence, or any other financial interests that any of the authors may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work. Address correspondence to Dr. K. Triantafyllias, ACURA Rheumatology Center, Kaiser-Wilhelm-Str. 9-11, 55543, Bad Kreuznach, Germany. Email:

We have read with great interest the letter of Verhoeven, , referring to our recent publication on the diagnostic value of optical spectral transmission (OST) in rheumatoid arthritis (RA). In our work we had described for the first time, to our knowledge, that OST values could be influenced not only by disease-associated factors (i.e., inflammatory activity) but also by patient-associated characteristics, such as sex, BMI, and age..
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http://dx.doi.org/10.3899/jrheum.201636DOI Listing
March 2021

Vascular Inflammation and Dysfunction in Lupus-Prone Mice-IL-6 as Mediator of Disease Initiation.

Int J Mol Sci 2021 Feb 25;22(5). Epub 2021 Feb 25.

Department of Nephrology and Rheumatology, University Center of Autoimmunity, Johannes-Gutenberg University Mainz, 55131 Mainz, Germany.

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients.

Methods: Here we investigated whether MRL- mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-, MRL-++, and previously generated MRL- mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage.

Results: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation.

Conclusion: Our findings demonstrate that the MRL- mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.
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http://dx.doi.org/10.3390/ijms22052291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956579PMC
February 2021

The Burden of Systemic Lupus Erythematosus in Germany: Incidence, Prevalence, and Healthcare Resource Utilization.

Rheumatol Ther 2021 Mar 5;8(1):375-393. Epub 2021 Feb 5.

BioPharmaceuticals Medical, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USA.

Introduction: We evaluated incidence, prevalence, costs, and healthcare utilization associated with systemic lupus erythematosus (SLE) in patients in Germany.

Methods: Adult patients with SLE were identified from the German Betriebskrankenkassen (BKK) health insurance fund database between 2009 and 2014. SLE incidence and prevalence were calculated for each year and extrapolated (age and sex adjusted) to the German population. The 2009 SLE population was followed through 2014. Healthcare utilization and costs for patients with SLE were calculated and compared with controls matched by age, sex, and baseline Charlson Comorbidity Index scores.

Results: This analysis included 1160 patients with SLE. Estimated SLE incidence between 2009 and 2014 ranged from 4.59 to 6.89 per 100,000 persons and prevalence ranged from 37.32 to 47.36 per 100,000. SLE incidence in Germany in 2014 was 8.82 per 100,000 persons; prevalence was 55.80 (corrected for right-censored data). At baseline, 12.8, 41.7, and 45.5% of patients were categorized as having mild, moderate, and severe SLE, respectively. Patients with SLE had greater mean (standard deviation [SD]) annual medical costs compared with matched controls 1 year after index diagnosis (€6895 [14,424] vs. €3692 [3994]; P < 0.0001) and in subsequent years. Patients with moderate or severe SLE had significantly more hospitalizations, outpatient visits, and prescription medication use compared with matched controls. Mean annual costs for 5 years ranged from €1890 to 3010, €4867 to 5876, and €8396 to 10,001 for patients with mild, moderate, and severe SLE, respectively.

Conclusions: SLE incidence in Germany increased 1.4-fold over 5 years. Patients with SLE have higher healthcare costs, and costs increase with baseline severity. Early and effective treatments may delay progression and reduce the burden of SLE.
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http://dx.doi.org/10.1007/s40744-021-00277-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991067PMC
March 2021

Alloimmune Myositis as Paraneoplastic Complication of an Oral Squamous Cell Carcinoma After Severe Chronic Graft vs Host Disease or a Manifestation of Chronic Graft vs Host Disease? A Case Report and Literature Discussion.

Transplant Proc 2021 Jan 19. Epub 2021 Jan 19.

Hematology, Oncology and Pneumology, UCT, University Medical Center Mainz, Mainz, Germany.

A 53-year-old female patient with acute myeloid leukemia developed severe chronic graft vs host disease (cGVHD) of the oral mucosa after allogeneic hematopoietic stem cell transplantation with leukoplakia and relapsing oral squamous cell carcinoma (SCC) of the tongue. cGVHD needed long-lasting immunosuppressive therapy; SCC was treated with radiation and surgery. Acute myeloid leukemia remained in complete remission. The patient developed a myositis with pain of all muscles as well as paraparesis with elevated creatine kinase and C-reactive protein and detection of antiskeletal muscle autoantibodies 3500 days after hematopoietic stem cell transplantation. No other clinical features of chronic GVHD were apparent at this time. Symptoms disappeared after treatment with corticosteroids but relapsed while tapering. Weekly therapy with the B-cell-depleting antibody rituximab was started and administered for 6 weeks. Symptoms disappeared again but partly returned after some weeks, so therapy with azathioprine was started. During therapy with azathioprine slow tapering of corticosteroids was possible and clinical symptoms remained absent. Here we present a case report and review of the literature on alloimmune myositis as paraneoplastic complication of an oral SCC of the tongue after severe chronic GVHD or as late manifestation of chronic GVHD itself.
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http://dx.doi.org/10.1016/j.transproceed.2020.11.010DOI Listing
January 2021

Current status of use of high throughput nucleotide sequencing in rheumatology.

RMD Open 2021 01;7(1)

Department of Internal Medicine, University Center of Autoimmunity, University Medical Center Mainz, Mainz, Germany.

Objective: Here, we assess the usage of high throughput sequencing (HTS) in rheumatic research and the availability of public HTS data of rheumatic samples.

Methods: We performed a semiautomated literature review on PubMed, consisting of an R-script and manual curation as well as a manual search on the Sequence Read Archive for public available HTS data.

Results: Of the 699 identified articles, rheumatoid arthritis (n=182 publications, 26%), systemic lupus erythematous (n=161, 23%) and osteoarthritis (n=152, 22%) are among the rheumatic diseases with the most reported use of HTS assays. The most represented assay is RNA-Seq (n=457, 65%) for the identification of biomarkers in blood or synovial tissue. We also find, that the quality of accompanying clinical characterisation of the sequenced patients differs dramatically and we propose a minimal set of clinical data necessary to accompany rheumatological-relevant HTS data.

Conclusion: HTS allows the analysis of a broad spectrum of molecular features in many samples at the same time. It offers enormous potential in novel personalised diagnosis and treatment strategies for patients with rheumatic diseases. Being established in cancer research and in the field of Mendelian diseases, rheumatic diseases are about to become the third disease domain for HTS, especially the RNA-Seq assay. However, we need to start a discussion about reporting of clinical characterisation accompany rheumatological-relevant HTS data to make clinical meaningful use of this data.
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http://dx.doi.org/10.1136/rmdopen-2020-001324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789458PMC
January 2021

Absence of Anti-Glomerular Basement Membrane Antibodies in 200 Patients With Systemic Lupus Erythematosus With or Without Lupus Nephritis: Results of the GOODLUPUS Study.

Front Immunol 2020 14;11:597863. Epub 2020 Dec 14.

Département de médecine interne, Centre Hospitalier Universitaire de Reims, Reims, France.

Introduction: Anti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.

Objective: The main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or without proliferative renal damage and compared to a healthy control group.

Methodology: This retrospective study was performed on SLE patients' sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer >6 U/ml).

Results: The cohort was composed of 100 SLE patients with proliferative LN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (>10 U/ml) by the automated technique, three sera were found "ambivalent" (>7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies.

Conclusion: Anti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.
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http://dx.doi.org/10.3389/fimmu.2020.597863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768036PMC
December 2020

Treatment of cytokine storm syndrome with IL-1 receptor antagonist anakinra in a patient with ARDS caused by COVID-19 infection: A case report.

Clin Case Rep 2020 Dec 15;8(12):2990-2994. Epub 2020 Sep 15.

Department of Internal Medicine I University Medical Center of the Johannes Gutenberg-University Mainz Germany.

The biological anakinra appears promising to halt cytokine storm syndrome seen in severe courses of COVID-19. However, immunosuppression with anakinra may facilitate sepsis, necessitating continuous screening for bacterial superinfections.
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http://dx.doi.org/10.1002/ccr3.3307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752410PMC
December 2020

B cell activating factor (BAFF): Structure, functions, autoimmunity and clinical implications in Systemic Lupus Erythematosus (SLE).

Autoimmun Rev 2021 Feb 14;20(2):102736. Epub 2020 Dec 14.

Department of Internal Medicine I, Division of Rheumatology and Clinical Immunology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Acura Rheumatology Center Rhineland Palatinate, Bad Kreuznach, Germany.

The B cell activating factor (BAFF), or B lymphocyte stimulator (BLyS), is a B cell survival factor which supports autoreactive B cells and prevents their deletion. BAFF expression is closely linked with autoimmunity and is enhanced by genetic alterations and viral infections. Furthermore, BAFF seems to be involved in adipogenesis, atherosclerosis, neuro-inflammatory processes and ischemia reperfusion (I/R) injury. BAFF is commonly overexpressed in Systemic Lupus Erythematosus (SLE) and strongly involved in the pathogenesis of the disease. The relationship between BAFF levels, disease activity and damage accrual in SLE is controversial, but growing evidence is emerging on its role in renal involvement. Belimumab, a biologic BAFF inhibitor, has been the first biologic agent licensed for SLE therapy so far. As Rituximab (RTX) has been shown to increase BAFF levels following B cell depletion, the combination therapy of RTX plus belimumab (being evaluated in two RCT) seems to be a valuable option for several clinical scenarios. In this review we will highlight the growing body of evidence of immune and non-immune related BAFF expression in experimental and clinical settings.
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http://dx.doi.org/10.1016/j.autrev.2020.102736DOI Listing
February 2021

Real-World Effectiveness of Belimumab in the Treatment of Systemic Lupus Erythematosus: Pooled Analysis of Multi-Country Data from the OBSErve Studies.

Rheumatol Ther 2020 Dec 18;7(4):949-965. Epub 2020 Nov 18.

GlaxoSmithKline, London, UK.

Introduction: The real-world effectiveness of belimumab for systemic lupus erythematosus (SLE) in six countries was evaluated in the OBSErve program. The aim of this post hoc analysis (GSK study 206351) was to pool individual patient OBSErve data to further evaluate the effectiveness of belimumab in a large sample of patients with SLE.

Methods: OBSErve (Argentina, Canada, Germany, Spain, Switzerland, and the USA) enrolled adults ≥ 18 years of age with SLE, who were prescribed belimumab as part of standard therapy (index: date of belimumab initiation). Endpoints (month 6 vs. index) included physician-assessed overall clinical response to belimumab in the overall population (primary) and high disease activity subgroups (secondary; patients with a SLEDAI-2K/SELENA-SLEDAI score ≥ 10 or patients with high anti-dsDNA or low complement at index); other secondary endpoints included changes in glucocorticosteroid (GCS) use and changes in disease activity. Factors associated with physician-assessed overall clinical response were also evaluated.

Results: In total, 830 patients were included in the overall population (mean [standard deviation (SD)] age: 41.9 [12.57] years; female: 89.3%; 60.4% from the USA). Nearly half (48.1%) of belimumab-treated patients experienced a ≥ 50% physician-assessed improvement in their overall manifestations, and 13% achieved a near normalization of their condition (equal to ≥ 80% improvement). Initiating belimumab while on high-dose (> 7.5 mg/day) GCS use was associated with ≥ 50% clinical improvement at month 6 (OR: 1.9, p = 0.003). Most (78.1%; n = 518/663) patients were able to reduce or discontinue their oral GCS dose after 6 months of belimumab, with a mean (SD) change of - 8.5 (10.74) mg/day prednisone-equivalent. The mean (SD) change from belimumab initiation in disease activity score (SLEDAI-2K/SELENA-SLEDAI) was - 5.7 (4.5; n = 344).

Conclusions: Belimumab improves clinical manifestations of SLE and is associated with GCS dose reductions in a real-world clinical setting, supporting the real-world effectiveness of belimumab for SLE.
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http://dx.doi.org/10.1007/s40744-020-00243-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695800PMC
December 2020

Patterns of fatigue and association with disease activity and clinical manifestations in systemic lupus erythematosus.

Rheumatology (Oxford) 2020 Nov 11. Epub 2020 Nov 11.

Centre National de Référence des Maladies Autoimmunes Systémiques Rares Est Sud-Ouest (RESO)-LUPUS, European Reference Networks (ERN) ReCONNET and RITA, Strasbourg.

Objective: The prevalence of fatigue is high in patients with systemic lupus erythematosus (SLE). In this study, we used latent class analysis to reveal patterns of fatigue, anxiety, depression and organ involvement in a large international cohort of SLE patients.

Methods: We used the Lupus BioBank of the upper Rhein to analyse patterns of fatigue using latent class analysis (LCA). After determining the optimal number of latent classes, patients were assigned according to model generated probabilities, and characteristics of classes were compared.

Results: A total of 502 patients were included. Significant fatigue, anxiety and depression were reported by 341 (67.9%), 159 (31.7%) and 52 (10.4%) patients, respectively. LCA revealed a first cluster (67.5% of patients) with low disease activity [median (25th-75th percentile interquartile range) Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI: 2 (0-4)], significant fatigue (55.5%, P < 0.0001), low anxiety (11.8%, P < 0.0001) and depression (0.9%, P < 0.0001). Cluster 2 (25.3%) also comprised patients with low disease activity [SELENA-SLEDAI: 2 (0-6)], but those patients had a very high prevalence of fatigue (100%, P < 0.0001), anxiety (89%, P < 0.0001) and depression (38.6%, P < 0.0001). Cluster 3 (7.2%) comprised patients with high disease activity [SELENA-SLEDAI: 12 (8-17), P < 0.0001] and high fatigue (72.2%, P < 0.0001) with low levels of anxiety (16.7%, P < 0.0001) and no depression (0%, P < 0.0001).

Conclusion: LCA revealed three patterns of fatigue with important practical implications. Based on these, it is crucial to distinguish patients with active disease (in whom remission will be achieved) from those with no or mild activity but high levels of fatigue, depression and anxiety, for whom psychological counselling should be prioritized.
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http://dx.doi.org/10.1093/rheumatology/keaa671DOI Listing
November 2020

Twelve-Week Internet-Based Individualized Exercise Program in Adults With Systemic Lupus Erythematosus: Protocol for a Randomized Controlled Trial.

JMIR Res Protoc 2020 Nov 3;9(11):e18291. Epub 2020 Nov 3.

Department of Rheumatology and Nephrology, University Medical Center Mainz, Mainz, Germany.

Background: Systemic lupus erythematosus is a systemic autoimmune disease, which is associated with high cardiovascular risk, a predisposition to metabolic disorders, muscle wasting, and fatigue. Exercise therapy has become an important part of the long-term treatment of comorbidities in systemic lupus erythematosus. Exercise can lead to various benefits in patients with systemic lupus erythematosus such as increased aerobic capacity and exercise tolerance, resulting in an increased quality of life, decreased depression, and decreased fatigue. At the moment, no evidence-based treatment guidelines that recommend exercise for patients with systemic lupus erythematosus exist. Also, the efficacy of different training programs requires further investigation.

Objective: This study focuses on the feasibility, efficacy, and safety of an internet-based exercise program in patients with systemic lupus erythematosus. Furthermore, we investigate the feasibility and efficiency of anaerobic training compared to aerobic training.

Methods: Overall, patients with systemic lupus erythematosus from the Division of Nephrology, Rheumatology, and Immunology outpatient clinic of the University Medical Center Mainz who are clinically stable status are included and randomized in an aerobic exercise group (n=10), anaerobic exercise group (n=10), or treatment as usual group (n=10). After completing initial clinical testing and physical fitness tests, patients undergo supervised 12-week online exercise programs, receiving weekly individualized training plans adapted to their physical performance. The primary outcome is change in physical fitness (VO2 peak) after 12 weeks compared to baseline. Secondary outcomes are disease activity measured via laboratory results (complement, autoantibodies) and questionnaires, as well as changes in muscle mass (anaerobic exercise group), results of the Chair-Stand test, and measurements of circulating cell-free DNA and extracellular vesicles.

Results: The study was registered in May 2019. Enrollment began in May 2019. Of 40 patients who were initially screened, 30 patients fulfilled the inclusion criteria and were included in the study; 1 participant withdrew prior to the start of the exercise program. Among the 25 patients who completed the study, no serious adverse events have been reported; 3 participants withdrew during the program (due to frequent colds, n=1; Crohn relapse, n=1; physical strain, n=1), and 1 participant has not yet completed the program. Data analysis is ongoing, and results are expected to be submitted for publication in January 2021.

Conclusions: We expect the online exercise intervention to be a feasible and efficient tool to provide regular individualized exercise for patients with systemic lupus erythematosus.

Trial Registration: ClinicalTrials.gov NCT03942718; http://clinicaltrials.gov/ct2/show/NCT03942718.

International Registered Report Identifier (irrid): DERR1-10.2196/18291.
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http://dx.doi.org/10.2196/18291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671835PMC
November 2020

Possible misclassification of cardiovascular risk by SCORE in antisynthetase syndrome: results of the pilot multicenter study RI.CAR.D.A.

Rheumatology (Oxford) 2021 Mar;60(3):1300-1312

Department of Rheumatology, ACURA Rheumatology Center, Bad Kreuznach, Germany.

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<0.001 and r = 0.664; P<0.001, respectively). Moreover, cfPWV correlated with BMI (Padj=0.001) and diabetes (Padj=0.043). CCA-RI and CCA-PI showed significant associations with creatine phosphokinase (r = 0.629; P=0.012 and r = 0.574; P=0.032, respectively) and ICA-RI and ICA-PI were higher in patients with lung involvement (both; P=0.039).

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.
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http://dx.doi.org/10.1093/rheumatology/keaa525DOI Listing
March 2021

Life-threatening disseminated enterovirus infection during combined rituximab and ibrutinib maintenance treatment for mantle cell lymphoma: a case report.

J Med Case Rep 2020 Aug 28;14(1):135. Epub 2020 Aug 28.

Department of Hematology, Medical Oncology & Pneumology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, D-55131, Mainz, Germany.

Background: Rituximab is a well-established component of treatment regimens for B-cell non-Hodgkin lymphoma. Rituximab binds the CD20 antigen on the surface of B lymphocytes, causing an enhanced clearance of malignant and benign B cells. Thus, rituximab leads to depletion of normal B lymphocytes as well, which can cause substantial immunodeficiency. Ibrutinib inhibits the Bruton tyrosine kinase and thereby B-cell activity. It is used for the treatment of different B-lymphocyte malignancies, such as mantle cell lymphoma. Recently, the combination of both drugs has been tested in various clinical scenarios.

Case Presentation: We present a case of disseminated enterovirus infection resulting from combined rituximab and ibrutinib maintenance treatment in a 57-year-old Caucasian patient. with mantle cell lymphoma. Initially presenting with myositis symptoms, further diagnostic investigation revealed myocarditis, enteritis, myeloencephalitis, and hepatitis. These organ manifestations led to potentially life-threatening complications such as rhabdomyolysis, delirium, and heart rhythm disturbances. After treatment with high-dose intravenous immunoglobulins, virus clearance was achieved and organ functions could be restored.

Conclusions: This case emphasizes the risk of combined therapy with rituximab/ibrutinib for severe immune-related side effects with the necessity of continuous patient monitoring. High-dose intravenous therapy should be considered as treatment for severe enterovirus infection. In severe enterovirus infections, we recommend subtyping for the development of efficient preventive and therapeutic strategies.
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http://dx.doi.org/10.1186/s13256-020-02457-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456041PMC
August 2020

Systemic lupus erythematosus and neutropaenia: a hallmark of haematological manifestations.

Lupus Sci Med 2020 07;7(1)

Department of Clinical Immunology and Internal Medicine, National Reference Center for autoimmune diseases (RESO), Strasbourg University Hospital, Strasbourg, France.

Objective: Systemic lupus is a chronic autoimmune disease characterised by its phenotypic heterogeneity. Neutropaenia is a frequent event in SLE occurring in 20%-40% of patients depending on the threshold value of neutrophil count. On a daily basis, the management of neutropaenia in SLE is difficult with several possible causes. Moreover, the infectious consequences of neutropaenia in SLE remain not well defined.

Methods: 998 patients from the Lupus BioBank of the upper Rhein (LBBR), a large German and French cohort of patients with SLE, mostly of Caucasian origin (83%), were included in this study. Neutropaenia was considered when neutrophil count was below 1800×10/L. An additional analysis of detailed medical records was done for 65 LBBR patients with neutropaenia.

Results: 208 patients with neutropaenia (21%) were compared with 779 SLE patients without neutropaenia. Neutropaenia in SLE was significantly associated with thrombocytopaenia (OR 4.11 (2.57-10.3)), lymphopaenia (OR 4.41 (2.51-11.5)) and low C3 (OR 1.91 (1.03-4.37)) in multivariate analysis. 65 representative patients with neutropaenia were analysed. Neutropaenia was moderate to severe in 38%, chronic in 31%, and both severe and chronic in 23% of cases. Moderate to severe and chronic neutropaenia were both associated with lymphopaenia and thrombopaenia. Chronic neutropaenia was also associated anti-Ro/SSA antibodies and moderate to severe neutropaenia with oral ulcers.

Conclusion: This study is to date the largest cohort to describe neutropaenia in SLE. Neutropaenia displays a strong association with other cytopaenias, suggesting a common mechanism. Chronic neutropaenia is associated with anti-Ro/SSA antibodies with or without identified Sjögren's disease.
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http://dx.doi.org/10.1136/lupus-2020-000399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333801PMC
July 2020

Systemic Lupus Erythematosus (SLE) Therapy: The Old and the New.

Rheumatol Ther 2020 Sep 2;7(3):433-446. Epub 2020 Jun 2.

Acura Rheumatology Center Rhineland Palatinate, Bad Kreuznach, Germany.

Despite recent improvements in the treatment of systemic lupus erythematosus (SLE), disease activity, comorbidities and drug toxicity significantly contribute to the risk of progressive irreversible damage accrual and increased mortality in patients with this chronic disease. Moreover, even lupus patients in remission often report residual symptoms, such as fatigue, which have a considerable impact on their health-related quality of life. In recent decades, SLE treatment has moved from the use of hydroxychloroquine, systemic glucocorticosteroids and conventional immunosuppressive drugs to biologic agents, of which belimumab is the first and only biologic agent approved for the treatment for SLE to date. Novel therapies targeting interferons, cytokines and their receptors, intracellular signals, plasma cells, T lymphocytes and co-stimulatory molecules are being evaluated. In the context of a holistic approach, growing evidence is emerging of the importance of correct lifestyle habits in the management of lupus manifestations and comorbidities. The aim of this paper is to provide an overview of current pharmacological and non-pharmacological treatment options and emerging therapies in SLE.
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http://dx.doi.org/10.1007/s40744-020-00212-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410873PMC
September 2020

Diagnostic Value of Optical Spectral Transmission in Rheumatoid Arthritis: Associations with Clinical Characteristics and Comparison with Joint Ultrasonography.

J Rheumatol 2020 09 1;47(9):1314-1322. Epub 2020 Apr 1.

From the ACURA Rheumatology Center Rhineland-Palatinate, Bad Kreuznach; Internal Medicine I, Department of Rheumatology and Clinical Immunology, Johannes Gutenberg University Medical Center; Internal Medicine I, Department of Gastroenterology, University Medical Center of Johannes Gutenberg University, Mainz, Germany.

Objective: To examine the value of optical spectral transmission (OST) in detecting joint inflammation in patients with rheumatoid arthritis (RA) and to evaluate whether OST correlates with certain patient characteristics.

Methods: OST measurements were performed in the metacarpophalangeal, proximal intraphalangeal, and wrist joints of 168 patients with RA and 114 controls. OST difference between the 2 groups was statistically examined and subsequently controlled for the effect of possible confounding factors. Diagnostic OST performance was tested by receiver-operating characteristics. Moreover, associations of OST with clinical and serological activity markers (patient group), joint ultrasound (US; patient subgroup) and various anthropometric and epidemiologic parameters (patient and control group) were evaluated by Spearman correlation coefficient and a generalized linear statistical adjustment model.

Results: OST was significantly higher in the RA group than in the control group, even after adjustment for confounding factors (1.89; 95% CI 0.709-3.070, p = 0.002). Taking US as a reference, area under the curve for all 1251 joints simultaneously was 0.67 (95% CI 0.631-0.709). In the patient group, correlation and adjustment analyses showed associations of OST with various disease activity markers [28-joint count Disease Activity Score (rho 0.313), swollen joint counts (rho 0.361), C-reactive protein (rho 0.389); all, p = 0.001], age (rho 0.276, p < 0.001), and osteoarthritis (p = 0.022). Moreover, OST associated with a power Doppler US score (rho 0.442; p = 0.001) and a greyscale US score (rho 0.591; p < 0.001). In both groups males had significantly higher OST values than females and OST associated moderately weakly with body mass index (rho patients 0.316, rho controls 0.24; all, p < 0.001).

Conclusion: Patients with RA showed higher OST values in comparison to controls. Moreover, OST associated with clinical, US, and laboratory disease activity markers.
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http://dx.doi.org/10.3899/jrheum.190650DOI Listing
September 2020

[Infection-triggered arthralgia and arthritis].

MMW Fortschr Med 2020 02;162(2):39-42

Schwerpunkt Rheumatologie und klinische Immunologie, Universitätsmedizin Mainz, Langenbeckstr. 1, D-55131, Mainz, Deutschland.

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http://dx.doi.org/10.1007/s15006-020-0104-9DOI Listing
February 2020

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course.

J Clin Med 2019 Nov 18;8(11). Epub 2019 Nov 18.

Department of Rheumatology, S. Maria Hospital-IRCCS, 42123 Reggio Emilia, Italy.

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.
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http://dx.doi.org/10.3390/jcm8112013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912490PMC
November 2019

Implementation of a Web-Based Work-Related Psychological Aftercare Program Into Clinical Routine: Results of a Longitudinal Observational Study.

J Med Internet Res 2019 06 18;21(6):e12285. Epub 2019 Jun 18.

Department for Psychosomatic Medicine and Psychotherapy, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.

Background: As inpatient medical rehabilitation serves to promote work ability, vocational reintegration is a crucial outcome. However, previous Web-based trials on coping with work-related stress have been limited to Web-based recruitment of study participants.

Objective: The aim of our study was to evaluate the implementation of an empirically supported transdiagnostic psychodynamic Web-based aftercare program GSA (Gesund und Stressfrei am Arbeitsplatz [Healthy and stress-less at the workplace])-Online plus into the clinical routine of inpatient medical rehabilitation, to identify characteristics of patients who have received the recommendation for GSA-Online plus, and to determine helpfulness of the intervention and satisfaction of the participants as well as improvement in quality of life and mental health status of the regular users of GSA-Online plus.

Methods: GSA-Online plus was prescribed by physicians at termination of orthopedic psychosomatic inpatient rehabilitation. Participants' use of the program, work-related attitudes, distress, and quality of life were assessed on the Web.

Results: In 2 rehabilitation centers, 4.4% (112/2562) of rehabilitants got a recommendation for GSA-Online plus during inpatient rehabilitation. Compared with usual person aftercare, the Web-based aftercare program was rarely recommended by physicians. Recommendations were made more frequently in psychosomatic (69/1172, 5.9%) than orthopedic (43/1389, 3.1%) rehabilitation (χ=11.845, P=.001, Cramér V=-0.068) and to younger patients (P=.004, d=0.28) with longer inpatient treatment duration (P<.001, r=-0.12) and extended sick leaves before inpatient medical rehabilitation (P=.004; Cramér V=0.072). Following recommendation, 77% (86/112) of rehabilitants participated in Web-based aftercare. Completers (50/86, 58%) reported statistically significant improvements between discharge of inpatient treatment and the end of the aftercare program for subjective work ability (P=.02, d=0.41), perceived stress (P=.01, d=-0.38), functioning (P=.002, d=-0.60), and life satisfaction (P=.008, d=0.42).

Conclusions: Physicians' recommendations of Web-based aftercare are well accepted by patients who derive considerable benefits from participation. However, a low rate of prescription compared with other usual aftercare options points to barriers among physicians to prescribing Web-based aftercare.
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http://dx.doi.org/10.2196/12285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604507PMC
June 2019

Fatigue in SLE: diagnostic and pathogenic impact of anti-N-methyl-D-aspartate receptor (NMDAR) autoantibodies.

Ann Rheum Dis 2019 09 11;78(9):1226-1234. Epub 2019 Jun 11.

Division of Rheumatology and Clinical Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Objectives: We explored the impact of circulating anti-N-methyl-D-aspartate receptor (NMDAR) antibodies on the severity of fatigue in patients with systemic lupus erythematosus (SLE).

Methods: Serum samples of 426 patients with SLE were analysed for the presence of antibodies to the NR2 subunit of the NMDAR. In parallel, the severity of fatigue was determined according to the Fatigue Scale for Motor and Cognitive functions questionnaire. In a subgroup of patients with SLE, the hippocampal volume was correlated with the levels of anti-NR2 antibodies. Isolated immunoglobulin G from patients with anti-NR2 antibodies were used for murine immunohistochemical experiments and functional assays on neuronal cell lines. Treatment effects were studied in 86 patients with lupus under belimumab therapy.

Results: We found a close correlation between the titre of anti-NR2 antibodies, the severity of fatigue, the clinical disease activity index (Systemic Lupus Erythematosus Disease Activity Index 2000) and anti-double stranded DNA antibodies-independently of the presence of neuropsychiatric lupus manifestations. Pathogenic effects could be demonstrated by (1) detection of anti-NR2 antibodies in the cerebrospinal fluid, (2) in situ binding of anti-NR2 antibodies to NMDAR of the hippocampus area and (3) distinct functional effects in vitro: downregulating the energy metabolism of neuronal cells without enhanced cytotoxicity. Treatment with belimumab for at least 6 months affected both the severity of fatigue and the levels of anti-NR2 antibodies.

Conclusion: The presence of anti-NR2 antibodies in patients with SLE with fatigue is a helpful diagnostic tool and may offer a major approach in the therapeutic management of this important disabling symptom in patients with SLE.
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http://dx.doi.org/10.1136/annrheumdis-2019-215098DOI Listing
September 2019

[Real World Management of Gouty Arthritis: Clinical, Epidemiological and Comorbidity Data from 4016 Patients in Rhineland-Palatinate, Germany].

Dtsch Med Wochenschr 2019 04 15;144(8):e51-e57. Epub 2019 Apr 15.

ACURA Rheuma-Kliniken, Bad Kreuznach, Deutschland.

Background: To examine clinical, comorbidity and demographic aspects of gout and to explore the routine clinical practice of gout treatment among general practitioners (G.P.'s) in southwest Germany.

Methods: Gout specific questionnaires were sent to all G.P.'s in Rhineland Palatinate (RL-P), through the Panel physicians' Association. Questionnaires consisted of items exploring epidemiological, medication and comorbidity data. Moreover, questions regarding clinical gout manifestations were included with an extra focus on therapy-refractory cases. Finally, G.P.'s were asked to rate the current care status of gout.

Results: Data from 4016 gout patients (age at diagnosis: 62.8 years, IQR 55 - 67.8) were collected. The majority of patients were male (75 %) with podagra being the most common gout manifestation (85 %). Chronic tophaceous courses were reported in 15 % (median 10 %, IQR 2 - 20) and spinal involvement in 2.7 % (median 0 %, IQR 0 - 2) of patients respectively. An average of 11.3 % cases (median 10 %, IQR 2.3 - 20) were defined as "hard-to-treat". However, biologic agents were not namely reported as applied treatments. 32 % of patients were diagnosed with gout by their G.P., whereas 68 % had to visit further physicians. A definite diagnosis could be reached after 3.1 months on average (median 0.3, IQR 0.1 - 1).

Conclusions: In the era of biologic therapies there is a need for optimization of gout management. Important targets are the shortening of diagnostic periods and the prevention of chronic disease courses. Critical awareness of the disease and its comorbidities, standardized treatment and patient-training could be important steps toward this direction.
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http://dx.doi.org/10.1055/a-0755-1341DOI Listing
April 2019

High cardiovascular risk in mixed connective tissue disease: evaluation of macrovascular involvement and its predictors by aortic pulse wave velocity.

Clin Exp Rheumatol 2019 Nov-Dec;37(6):994-1002. Epub 2019 Apr 2.

ACURA Rheumatology Clinics, Bad Kreuznach, and Division of Rheumatology and Clinical Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Germany.

Objectives: Macrovascular involvement and cardiovascular (CV) risk has not been sufficiently studied in mixed connective tissue disease (MCTD). In particular, the gold standard assessment method of aortic stiffness carotid-femoral pulse wave velocity (cfPWV) has never been evaluated in patients with this disease. The aims of the present study were therefore to examine cfPWV in MCTD and to evaluate its associations with MCTD-associated markers and traditional CV risk factors.

Methods: Measurements of cfPWV were performed in 43 MCTD patients and 107 healthy controls. The difference between cfPWV in the two groups was statistically examined and subsequently controlled for the effect of possible confounding factors. The association of cfPWV with MCTD-associated organ involvement, routine laboratory parameters and immunoserological markers was also evaluated. Finally, the relationship of cfPWV with medications and traditional CV risk factors was examined.

Results: Adjusted statistical analyses for confounding factors showed significantly higher cfPWV values in MCTD patients in comparison to controls (padj<0.001). cfPWV correlated in both the patients and the control group significantly with age (rho=0.69, p<0.001 and rho=0.67, p<0.001 respectively) and diastolic arterial pressure (padj=0.024 and padj=0.032 respectively). Moreover, cfPWV correlated in the control group with systolic and mean arterial pressure (padj<0.001 and p=0.002 respectively). Finally, higher cfPWV values could be documented in the subset of MCTD patients without lung involvement (padj=0.007).

Conclusions: Patients with MCTD have significantly higher aortic stiffness and thus CV risk in comparison to controls. Except for the disease itself, age and blood pressure were the main predictors of cfPWV.
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December 2019

Vascular stiffness: influencing factors on carotid-femoral pulse wave velocity in systemic lupus erythematosus.

Clin Exp Rheumatol 2020 Jan-Feb;38(1):74-81. Epub 2019 Mar 18.

Department of Internal Medicine I, Division of Rheumatology and Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Germany.

Objectives: Patients with systemic lupus erythematosus (SLE) are under increased risk for cardiovascular events (CVE) and mortality. Aortic stiffness, as measured by carotid-femoral pulse wave velocity (cfPWV), has been shown to predict CVE and mortality in the general population. The aim of the present study was to examine the factors associated with cfPWV in patients with SLE and to determine differences of SLE patients in comparison to healthy controls.

Methods: 125 patients with SLE and 104 controls were included. Demographic, medication and cardiovascular risk factor data were collected from all participants. Furthermore, clinical and laboratory SLE associated parameters were documented in the patients' group. All subjects underwent measurements of blood pressure and cfPWV.

Results: Interestingly, only age (β=0.55; p<0.001), mean arterial pressure (MAP) (β=0.29; p<0.001) and estimated glomerular filtration rate (eGFR) (β=-0.20; p=0.033) were associated independently with cfPWV in patients with SLE. Moreover, there was no difference of cfPWV between patients with SLE and controls before (p=0.301) and after adjustment for disparities between the groups (p=0.671).

Conclusions: Vascular stiffness in patients with SLE seems to be independent from SLE-related factors and from most traditional CVRF and is mainly associated with age, MAP and renal function defined as eGFR. There is an independent correlation between eGFR and cfPWV in a SLE population with a widely normally ranged eGFR. There is no difference of cfPWV between patients with SLE and controls.
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March 2020

Predictors of fatigue and severe fatigue in a large international cohort of patients with systemic lupus erythematosus and a systematic review of the literature.

Rheumatology (Oxford) 2019 06;58(6):987-996

Centre National de Référence des Maladies Autoimmunes Systémiques Rares Est Sud-Ouest (RESO)-LUPUS.

Objective: Fatigue is reported in up to 90% of patients with SLE. This study was conducted to identify the determinants associated with fatigue in a large cohort of patients with SLE, as well as to provide a systematic review of the literature.

Methods: Patients from the Lupus BioBank of the upper Rhein, a large German-French cohort of SLE patients, were included in the FATILUP study if they fulfilled the 1997 ACR criteria for SLE and had Fatigue Scale for Motor and Cognitive Functions scores collected. Multivariate logistic regression analyses were performed to assess the determinants of fatigue and severe fatigue.

Results: A total of 570 patients were included (89.1% female). The median age was 42 years (interquartile range 25-75: 34-52). The median value of the SAfety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI was 2 (0-4). Fatigue was reported by 386 patients (67.7%) and severe fatigue by 209 (36.7%). In multivariate analyses, fatigue was associated with depression [odds ratio (OR): 4.72 (95% CI: 1.39-16.05), P = 0.01], anxiety [OR: 4.49 (95% CI: 2.60-7.77), P < 0.0001], glucocorticoid treatment [OR: 1.59 (95% CI 1.05-2.41), P = 0.04], SELENA-SLEDAI scores [OR: 1.05 (95% CI: 1.00-1.12) per 1 point increase, P = 0.043] and age at sampling [OR: 1.01 (95% CI: 1.00-1.03) per 1 year increase, P = 0.03]. Severe fatigue was independently associated with anxiety (P < 0.0001), depression (P < 0.0001), glucocorticoid treatment (P = 0.047) and age at sampling (P = 0.03).

Conclusion: Both fatigue and severe fatigue are common symptoms in SLE, and are strongly associated with depression and anxiety. Disease activity and the use of glucocorticoids were also independently associated with fatigue, although more weakly.
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http://dx.doi.org/10.1093/rheumatology/key398DOI Listing
June 2019

Nailfold Capillaroscopy Characteristics of Antisynthetase Syndrome and Possible Clinical Associations: Results of a Multicenter International Study.

J Rheumatol 2019 03 15;46(3):279-284. Epub 2018 Nov 15.

From the Rheumatology Unit, Azienda Policlinico of Modena, University of Modena and Reggio Emilia, Modena, Italy; ACURA Rheumatology Center, Bad Kreuznach, Germany; Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDiVAL, University of Cantabria, Santander, Spain; Rheumatology Division, University Hospital of Frankfurt, Frankfurt, Germany; Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Mexico City, Mexico; Servicio de Reumatología, Hospital Universitario La Paz, Madrid, Spain; Interdisciplinary Department of Medicine (DIM), Rheumatology Unit, University of Bari, Bari, Italy; Rheumatology Department, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria (IIS) Princesa, Madrid; Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Universidad Autonoma de Barcelona, on behalf of the GEAS group, Barcelona, Spain; Department of Experimental and Clinical Medicine, and Department of Medical and Surgical Critical Care, Section of Dermatology, University of Florence, Florence; Unità Operativa Complessa (UOC) Reumatologia, Ospedale San Camillo-Forlanini, Rome; ACURA Centre for Rheumatic Diseases, Baden-Baden, Germany; Rheumatology Department, Città Della Salute e della Scienza, Torino; Division of Rheumatology, University and Institute for Research and Health Care (IRCCS) Policlinico S. Matteo Foundation, Pavia, Italy; Servicio de Reumatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Dermatology Clinic, University Hospital of Trieste; Department of Pneumology and Respiratory Intermediate Care Unit, University Hospital of Cattinara, Trieste; Rheumatology Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Trieste, Trieste, Italy; Medizinische Klinik A, Klinikum der Stadt, Ludwigshafen, Germany; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, San Martino Polyclinic Hospital IRCCS Genoa, Genoa, Italy; Interstitial and Rare Lung Disease Unit, Ruhrlandklinik University Hospital, University of Duisburg-Essen, Essen, Germany; UOC Reumatologia, Azienda Ospedaliero Universitaria S. Anna, University of Ferrara, Italy; Department for Rheumatology and Clinical Immunology, St. Josef Krankenhaus, University Clinic, Essen, Germany; Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa; Department of Internal Medicine, Rheumatology and Clinical Immunology, University Hospital Johannes-Gutenberg, Mainz, Germany; University of Ghent, Ghent University Hospital, Ghent, Belgium.

Objective: To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease.

Methods: We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non-anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody-negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures.

Results: NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP.

Conclusion: NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.
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http://dx.doi.org/10.3899/jrheum.180355DOI Listing
March 2019

[Current patient care of giant cell arteritis in Rhineland-Palatinate].

Z Rheumatol 2019 Sep;78(7):677-684

Schwerpunkt Rheumatologie und klinische Immunologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Langenbeckstraße 1, 55131, Mainz, Deutschland.

Background: Giant cell arteritis (GCA) is one of the most common forms of inflammatory vasculitis in older patients. Because of possible irreversible vision deterioration, a fastest possible diagnosis and therapy is of absolute importance. To date, there are still no reliable data to obtain an initial assessment of the outpatient health care situation of patients diagnosed with GCA in Rhineland-Palatinate.

Methods: The specialists (neurologists, rheumatologists, ophthalmologists and general practitioners) participating in the statewide rheumatology network ADAPTHERA were questioned with the help of a questionnaire regarding disease frequency, activity, drug therapy and possible comorbidities. In addition, the collected data were compared and supplemented by the ambulatory coding of the Association of Statutory Health Insurance Physicians in Rhineland-Palatinate.

Results: Based on the information provided by general practitioners, 272 GCA patients were treated in Rhineland-Palatinate during the survey period. The average duration of the disease until diagnosis was 3.6 (SD ± 4.8) months. Drug therapy in the form of glucocorticoids was in first place followed by methotrexate, acetylsalicylic acid (ASA) and azathioprine. Cardiovascular diseases, chronic pain syndromes, depression, osteoporosis and diabetes mellitus were also described as comorbidities.

Conclusion: The majority of patients with GCA are being cared for by general practitioners (GP). Long-term therapy and timely rheumatological co-treatment seem to be problematic. The primary care providers expressed their wishes for rheumatological training and further education measures. In terms of diagnosis and treatment, there is a demand to implement a "vasculitis fast-track" module.
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http://dx.doi.org/10.1007/s00393-018-0484-8DOI Listing
September 2019