Publications by authors named "Laurent Arnaud"

193 Publications

Tolerance of COVID-19 vaccination in patients with systemic lupus erythematosus: the international VACOLUP study.

Lancet Rheumatol 2021 Jul 21. Epub 2021 Jul 21.

Service de rhumatologie, Centre National de Référence des Maladies Auto-immunes Systémiques Rares Est Sud-Ouest (RESO), Hôpitaux Universitaires de Strasbourg, 67098 Strasbourg, France.

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http://dx.doi.org/10.1016/S2665-9913(21)00221-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294805PMC
July 2021

Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial.

Rheumatology (Oxford) 2021 Jul 23. Epub 2021 Jul 23.

Vascular Research Center Marseille, INSERM, INRA, Aix-Marseille University, MARSEILLE, FRANCE.

Objective: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients.

Methods: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution®800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hands function, vasculopathy, hands pain, skin fibrosis, sensitivity of the finger' pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction and the safety.

Results: 40 patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 month-follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 ± 12.2 in the AD-SVF group vs -7.6 ± 13.2 in the placebo group). At 6 months, hand function improved in both groups.

Conclusion: This study showed an improvement of hand function in both groups other time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap, should be encouraged to accurately assess the benefit of AD-SVF therapy.

Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.
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http://dx.doi.org/10.1093/rheumatology/keab584DOI Listing
July 2021

Incidence and predictors of COVID-19 and flares in patients with rare autoimmune diseases: a systematic survey and serological study at a national reference center in France.

Arthritis Res Ther 2021 07 13;23(1):188. Epub 2021 Jul 13.

Service de rhumatologie, Service de rhumatologie, Hôpitaux Universitaires de Strasbourg et Université de Strasbourg, 1 avenue Molière BP 83049, 67098, Strasbourg cedex, France.

Background: The risk of severe COVID-19 and its determinants remain largely unknown in patients with autoimmune and inflammatory rheumatic diseases. The objective of this study was to assess the prevalence of COVID-19 infection in patients followed for rare autoimmune diseases as well as the predictors of COVID-19 and disease flare-ups.

Methods: Cross-sectional phone survey from April 9, 2020, to July 2, 2020, during which patients with autoimmune diseases followed at the National Reference Center for Rare Autoimmune diseases of Strasbourg were systematically contacted by phone and sent a prescription for a SARS-CoV-2 serology.

Results: One thousand two hundred thirty-two patients were contacted. One thousand fifty-five patients with a confirmed diagnosis of systemic autoimmune disease were included (4 unreachable, 4 moves abroad, 5 deaths before pandemic, 50 without consent, and 114 without autoimmune disease). Among them, 469 (44.5%) patients were tested for SARS-CoV-2 serology. Thirty-nine patients (7.9%) had SARS-CoV-2 infection (either through chest CT-scan [n = 5], RT-PCR on nasopharyngeal swab [n = 14], or serology [n = 31]) among the 496 who underwent at least one of those 3 diagnosis modalities. Of the 39 proven cases, 33 had clinical manifestations (6 asymptomatic patients were diagnosed through systematic serology testing), 31 were managed by home care, 3 were hospitalized due to a need for oxygenation, two required admission to an intensive care unit, and one died. Among patients with confirmed SARS-CoV-2 infection, reported flares were more frequent than in uninfected patients (26.3% [10/38] vs. 7.0% [32/457], p < 0.0001). Preventive sick leave had no significant impact on the prevalence of SARS-CoV-2 infection (5.8% [3/53]) compared to work continuation (7.6% [30/397], p = 0.64). Overall, the seroprevalence of SARS-CoV-2 was 6.6% (31/469) which was numerically lower to the Grand-Est general population estimated to be 9.0%.

Conclusions: This systematic survey of more than 1000 patients with rare systemic autoimmune diseases reports a low prevalence of proven SARS-CoV-2 infection and very rare severe infections, probably related to good compliance with prophylactic measures in these patients.
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http://dx.doi.org/10.1186/s13075-021-02565-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276223PMC
July 2021

Refining "Long-COVID" by a Prospective Multimodal Evaluation of Patients with Long-Term Symptoms Attributed to SARS-CoV-2 Infection.

Infect Dis Ther 2021 Sep 10;10(3):1747-1763. Epub 2021 Jul 10.

Rheumatology Department, Centre Hospitalier Universitaire de Strasbourg, 1 Avenue Molière, 67098, Strasbourg, France.

Introduction: COVID-19 long-haulers, also decribed as having "long-COVID" or post-acute COVID-19 syndrome, represent 10% of COVID-19 patients and remain understudied.

Methods: In this prospective study, we recruited 30 consecutive patients seeking medical help for persistent symptoms (> 30 days) attributed to COVID-19. All reported a viral illness compatible with COVID-19. The patients underwent a multi-modal evaluation, including clinical, psychologic, virologic and specific immunologic assays and were followed longitudinally. A group of 17 convalescent COVID-19 individuals without persistent symptoms were included as a comparison group.

Results: The median age was 40 [interquartile range: 35-54] years and 18 (60%) were female. At a median time of 152 [102-164] days after symptom onset, fever, cough and dyspnea were less frequently reported compared with the initial presentation, but paresthesia and burning pain emerged in 18 (60%) and 13 (43%) patients, respectively. The clinical examination was unremarkable in all patients, although the median fatigue and pain visual analog scales were 7 [5-8] and 5 [2-6], respectively. Extensive biologic studies were unremarkable, and multiplex cytokines and ultra-sensitive interferon-α2 measurements were similar between long-haulers and convalescent COVID-19 individuals without persistent symptoms. Using SARS-CoV-2 serology and IFN-γ ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with evidence of a lack of immune response, or a waning immune response, in two patients. Finally, psychiatric evaluation showed that 11 (36.7%), 13 (43.3%) and 9 (30%) patients had a positive screening for anxiety, depression and post-traumatic stress disorder, respectively.

Conclusions: Half of patients seeking medical help for post-acute COVID-19 syndrome lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity, or not, had no consequence on the clinical or biologic characteristics of post-acute COVID-19 syndrome patients, all of whom reported severe fatigue, altered quality of life and psychologic distress.
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http://dx.doi.org/10.1007/s40121-021-00484-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270770PMC
September 2021

Inter-center comparison of good manufacturing practices-compliant stromal vascular fraction and proposal for release acceptance criteria: a review of 364 productions.

Stem Cell Res Ther 2021 07 1;12(1):373. Epub 2021 Jul 1.

Swiss Stem Cell Foundation, Gentilino, Lugano, Switzerland.

Background: Even though the manufacturing processes of the stromal vascular fraction for clinical use are performed in compliance with the good manufacturing practices applying to advanced therapy medicinal products, specifications related to stromal vascular fraction quality remain poorly defined. We analyzed stromal vascular fraction clinical batches from two independent good manufacturing practices-compliant manufacturing facilities, the Swiss Stem Cell Foundation (SSCF) and Marseille University Hospitals (AP-HM), with the goal of defining appropriate and harmonized release acceptance criteria.

Methods: This retrospective analysis reviewed the biological characteristics of 364 batches of clinical-grade stromal vascular fraction. Collected data included cell viability, recovery yield, cell subset distribution of stromal vascular fraction, and microbiological quality.

Results: Stromal vascular fraction from SSCF cohort demonstrated a higher viability (89.33% ± 4.30%) and recovery yield (2.54 × 10 ± 1.22 × 10 viable nucleated cells (VNCs) per mL of adipose tissue) than stromal vascular fraction from AP-HM (84.20% ± 5.96% and 2.25 × 10 ± 1.11 × 10 VNCs per mL). AP-HM batches were significantly less contaminated (95.71% of sterile batches versus 74.15% for SSCF batches). The cell subset distribution was significantly different (higher proportion of endothelial cells and lower proportion of leukocytes and pericytes in SSCF cohort).

Conclusions: Both centers agreed that a good manufacturing practices-compliant stromal vascular fraction batch should exert a viability equal or superior to 80%, a minimum recovery yield of 1.50 × 10 VNCs per mL of adipose tissue, a proportion of adipose-derived stromal cells at least equal to 20%, and a proportion of leukocytes under 50%. In addition, a multiparameter gating strategy for stromal vascular fraction analysis is proposed.
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http://dx.doi.org/10.1186/s13287-021-02445-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252207PMC
July 2021

Digital health, big data and smart technologies for the care of patients with systemic autoimmune diseases: Where do we stand?

Autoimmun Rev 2021 Aug 9;20(8):102864. Epub 2021 Jun 9.

Department of neuroradiology, A. Rothshield Foundation Hospital, Paris, France. Electronic address:

The past decade has seen tremendous development in digital health, including in innovative new technologies such as Electronic Health Records, telemedicine, virtual visits, wearable technology and sophisticated analytical tools such as artificial intelligence (AI) and machine learning for the deep-integration of big data. In the field of rare connective tissue diseases (rCTDs), these opportunities include increased access to scarce and remote expertise, improved patient monitoring, increased participation and therapeutic adherence, better patient outcomes and patient empowerment. In this review, we discuss opportunities and key-barriers to improve application of digital health technologies in the field of autoimmune diseases. We also describe what could be the fully digital pathway of rCTD patients. Smart technologies can be used to provide real-world evidence about the natural history of rCTDs, to determine real-life drug utilization, advanced efficacy and safety data for rare diseases and highlight significant unmet needs. Yet, digitalization remains one of the most challenging issues faced by rCTD patients, their physicians and healthcare systems. Digital health technologies offer enormous potential to improve autoimmune rCTD care but this potential has so far been largely unrealized due to those significant obstacles. The need for robust assessments of the efficacy, affordability and scalability of AI in the context of digital health is crucial to improve the care of patients with rare autoimmune diseases.
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http://dx.doi.org/10.1016/j.autrev.2021.102864DOI Listing
August 2021

Prescription strategy of antimalarials in cutaneous and systemic lupus erythematosus: an international survey.

Ther Adv Musculoskelet Dis 2021 19;13:1759720X211002595. Epub 2021 May 19.

Service de Rhumatologie, Centre National de Référence des Maladies Autoimmunes et Systémiques Rares (RESO), Hôpital de Hautepierre, 1 Avenue Molière BP 83049, Strasbourg Cedex, 67098, France.

Background: Antimalarial agents (AMs), mainly hydroxychloroquine (HCQ) and chloroquine, are the cornerstone of treatment of cutaneous and systemic lupus erythematosus. However, many aspects of AM prescription remain empirical. The aim of this study was to assess the modalities of AM prescription among physicians treating patients with lupus and to verify the assumption that AM use is heterogeneous and frequently at variance with international guidelines.

Methods: We performed an international cross-sectional study among physicians involved in lupus care, using a web-based survey (from September 2019 to July 2020) addressing the main controversial aspects of AM prescription.

Results: A total of 298 physicians [median age: 42 (interquartile range: 17) years, mainly internists and rheumatologists] from 35 countries participated to the study. A total of 93% used HCQ as the first-line AM, 69.5% used fixed doses of AMs (mainly 400 mg/day for HCQ) and only 37.9% adjusted the dose in case of renal failure. The main reasons for measuring HCQ blood levels were suspected non-adherence (55.7%) and failure of AM treatment (34.1%). In case of AM failure, 58.0% added an immunosuppressive agent. In case of remission, 49.7% maintained the same dose of AM, whereas 48.3% reduced the dose. One-third of respondents reported not following the American screening guidelines on AM retinal toxicity and 40.9% started retinal screening from the first year of treatment.

Conclusion: This study highlights the strong heterogeneity of AM prescription in lupus, as well as several key unmet needs regarding AMs. This may be improved by developing more comprehensive recommendations and favoring dissemination among physicians.
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http://dx.doi.org/10.1177/1759720X211002595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138289PMC
May 2021

Cluster analysis reveals 3 main patterns of behavior towards SARS-CoV-2 vaccination in patients with autoimmune and inflammatory diseases.

Rheumatology (Oxford) 2021 May 13. Epub 2021 May 13.

Service de rhumatologie, Centre National de Référence des Maladies Auto-immunes Systémiques Rares Est Sud-Ouest RESO, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Introduction: Given the COVID19 pandemic, it is crucial to understand the underlying behavioral determinants of SARS-CoV-2 vaccine hesitancy in patients with autoimmune or inflammatory rheumatic diseases AIIRD. We aimed to analyze patterns of behaviors regarding SARS-CoV-2 vaccination in AIIRD patients, as a mean to identify pragmatic actions to increase vaccine coverage in this population.

Methods: Data of 1258 AIIRD patients were analyzed using univariate and multivariate logistic regression models, to identify variables associated independently with the willingness to get vaccinated against SARS-CoV-2. Subsets of patients showing similar behaviors towards SARS-CoV-2 vaccination were characterized using cluster analysis.

Results: Hierarchical cluster analysis identified 3 distinct clusters of AIIRD patients. Three predominant patients' behavior towards SARS-COV-2 vaccination: 'voluntary', 'hesitant' and 'suspicious' were identified. While vaccine willingness was significantly different across the 3 clusters p< 0.0001, there was no difference regarding the fear to get COVID-19 p= 0.11, the presence of co-morbidities p= 0.23, the use of glucocorticoids p= 0.21 or the immunocompromised status p= 0.63. However, patients from cluster #3 'suspicious' were significantly more concerned about vaccination, the use of a new vaccine technology, the lack of hindsight regarding COVID vaccination and potential financial links with pharmaceutical companies p< 0.0001 in all than in the other 2 clusters.

Discussion: Importantly, the differences between patients' behaviors are not related to the fear of getting COVID-19 or to any state of frailty, but point out to specific concerns about vaccination. This study may serve as a basis for improved communication, to increase COVID-19 vaccine coverage in AIIRD patients.
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http://dx.doi.org/10.1093/rheumatology/keab432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194533PMC
May 2021

Significance of Sjögren's syndrome and anti-cN1A antibody in myositis patients.

Rheumatology (Oxford) 2021 May 11. Epub 2021 May 11.

Service de Physiologie, Explorations Fonctionnelles Musculaires, CHU de Strasbourg, Strasbourg, France.

Objective: We recently recorded a high prevalence of inclusion body myositis (IBM) in patients with Sjögren's syndrome (SS). Whether myositis patients with SS differ from myositis patients without SS in terms of the characteristics of the myositis is currently unknown. Anti-cytosolic 5'-nucleotidase 1 A (cN1A) has recently been proposed as a biomarker for IBM but is also frequent in SS. Whether anti-cN1A is independently associated with IBM is still an open question. We aimed to assess the significance of SS and anti-cN1A in myositis patients.

Methods: Cumulative data on all myositis patients (EULAR/ACR 2017 criteria) screened for SS (ACR/EULAR 2016 criteria) in a single center were analyzed. Ninety-nine patients were included, covering the whole spectrum of EULAR/ACR 2017 myositis subgroups and with a median follow-up of 6 years [range 1.0-37.5]. The 34 myositis patients with SS (myositis/SS+) were compared with the 65 myositis patients without SS (myositis/SS-).

Results: IBM was present in 24% of the myositis/SS+ patients vs 6% of the myositis/SS- group (p = 0.020). None of the IBM patients responded to treatment, whether they had SS or not. Anti-cN1A was more frequent in myositis/SS+ patients (38% vs 6%, p = 0.0005), independently of the higher prevalence of IBM in this group (multivariate p-value: 0.02). Anti-cN1A antibody specificity for IBM was 0.96 [95% CI, 0.87-0.99] in the myositis SS- group but dropped to 0.70 [95% CI, 0.48-0.85] in the myositis SS/+ group.

Interpretation: In myositis patients, SS is associated with IBM and with anti-cN1A antibodies, independently of the IBM diagnosis. As a consequence, anti-cN1A has limited specificity for IBM in myositis patients with SS.
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http://dx.doi.org/10.1093/rheumatology/keab423DOI Listing
May 2021

Endorsement of the OMERACT core domain set for shared decision making interventions in rheumatology trials: Results from a multi-stepped consensus-building approach.

Semin Arthritis Rheum 2021 Jun 6;51(3):593-600. Epub 2021 Apr 6.

Institute for Work & Health, Institute Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.

Objective: To gain consensus on the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials of shared decision making (SDM) interventions.

Methods: The process followed the OMERACT Filter 2.1 methodology, and used consensus-building methods, with patients involved since the inception. After developing the draft core domain set in previous research, we conducted five steps: (i) improving the draft core domain set; (ii) developing and disseminating white-board videos to promote its understanding; (iii) conducting an electronic survey to gather feedback on the draft core domain set; (iv) finalizing the core domain set and developing summaries, a plenary session video and discussion boards to promote its understanding; and (v) conducting virtual workshops with voting to endorse the core domain set.

Results: A total of 167 participants from 28 countries answered the survey (62% were patients/caregivers). Most participants rated domains as relevant (81%-95%) and clear (82%-93%). A total of 149 participants (n = 48 patients/caregivers, 101 clinicians/researchers) participated in virtual workshops and voted on the proposed core domain set which received endorsement by 95%. Endorsed domains are: 1- Knowledge of options, their potential benefits and harms; 2- Chosen option aligned with each patient's values and preferences; 3- Confidence in the chosen option; 4- Satisfaction with the decision-making process; 5- Adherence to the chosen option and 6- Potential negative consequences of the SDM intervention.

Conclusion: We achieved consensus among an international group of stakeholders on the OMERACT core domain set for rheumatology trials of SDM interventions. Future research will develop the Core Outcome Measurement Set.

Clinical Significance: Prior to this study, there had been no consensus on the OMERACT core domain set for SDM interventions. The current study shows that the OMERACT core domain set achieved a high level of endorsement by key stakeholders, including patients/caregivers, clinicians and researchers.
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http://dx.doi.org/10.1016/j.semarthrit.2021.03.017DOI Listing
June 2021

Prevalence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and spatial association with quarries in a French Northeast region.

Arthritis Rheumatol 2021 Apr 21. Epub 2021 Apr 21.

Department of Rheumatology, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Hôpitaux Universitaires de Strasbourg, F-67000, Strasbourg, France.

Objective: Silica is one of the strongest environmental substances linked with autoimmunity. The aim of this study was to assess the prevalence of granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and renal limited vasculitis (RLV) in a French northeast region, and their geospatial association with quarries.

Methods: Potential ANCA-Associated Vasculitis (AAV) cases were identified using three sources: hospital records, immunology laboratories and the National Health Insurance System. Patients who resided in Alsace on January 1, 2016 and fulfilled ACR AAV criteria or Chapel Hill Consensus Conference 2012 definition were included. Incomplete case ascertainment was corrected using capture-recapture analysis. The spatial association between the number of cases and quarries in each administrative entity was assessed using geographical weighted regression (GWR).

Results: From 910 potential AAV cases, we identified 185 patients meeting inclusion criteria: 120 GPA, 35 MPA, 30 RLV. The number of cases missed by any source was 6.4 (95%CI 3.6-11.5). Accordingly, the 2016 estimated prevalence in Alsace was 65.5 cases per million inhabitants (95%CI 47.3-93.0) for GPA, 19.1 (95%CI 11.3-34.3) for MPA, and 16.8 (95%CI 8.7-35.2) for RLV. The risk of AAV was significantly increased in communes with quarries (OR: 2.51 [95%CI: 1.66-3.80]) and GWR revealed a significant spatial association between quarries and GPA cases (p = 0.039), and, regarding ANCA serotype, between quarries and both PR3-AAV (p = 0.04) and MPO-AAV (p = 0.03)."

Conclusion: In a region with a high density of quarries, the spatial association of AAV with quarries supports the role of silica as a specific environmental factor.
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http://dx.doi.org/10.1002/art.41767DOI Listing
April 2021

Follow-up of COVID-19 patients: LA is transient but other aPLs are persistent.

Autoimmun Rev 2021 Jun 16;20(6):102822. Epub 2021 Apr 16.

Service d'Immunologie Clinique-Médecine Interne, Centre National de Référence des Maladies Auto-immunes et Systémiques Rares Est/Sud-Ouest RESO, Hôpitaux Universitaires de Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2021.102822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050395PMC
June 2021

Living with systemic lupus erythematosus in 2020: a European patient survey.

Lupus Sci Med 2021 04;8(1)

Service de rhumatologie, Centre National de Références des Maladies Auto-immunes et Systémique (RESO), Hopitaux universitaires de Strasbourg, Strasbourg, France

Objective: The aim of this study was to analyse the 2020 burden of Systemic Lupus Erythematosus (SLE) in Europe, from the patients' perspective.

Methods: In May 2020, Lupus Europe, the European umbrella patient association for SLE, designed and disseminated a multilingual anonymous online survey to individuals with a self-reported physician's diagnosis of SLE living in Europe.

Results: Data from 4375 SLE survey respondents (95.9% women, median age: 45 (IQR: 36-54) years, 70.7% Caucasians) from 35 European countries were analysed. The median age at SLE diagnosis was 30 years (IQR: 22-40) and the median diagnosis delay was 2 years (IQR: 0-6). The most commonly affected organ-systems included the joints (81.8%) and skin (59.4%), with renal involvement in 30%. Another diagnosis was given before that of SLE in 45.0%, including psychological/mental disorders in 9.1% and fibromyalgia in 5.9%. The median number of symptoms reported was 9 (IQR: 6-11) out of 21, with fatigue most common (85.3%) and most bothersome. The median number of SLE-related medications was 5 (IQR: 3-7), including antimalarials (75%), oral glucocorticoids (52.4%), immunosuppressants (39.8%) and biologics (10.9%). Respondents reported significant impact over their studies, career and emotional/sexual life in 50.7%, 57.9% and 38.2%, respectively. Appropriate access to care was highly variable across countries and care component.

Conclusion: This survey underlines the 2020 burden and strong heterogeneity in the care of SLE across Europe, from the patient's perspective. Altogether, these data may prove crucial to physicians, patients and policy-makers to improve the diagnosis and management of this rare and complex disease.
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http://dx.doi.org/10.1136/lupus-2020-000469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051432PMC
April 2021

Correspondence on 'Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry'.

Ann Rheum Dis 2021 Feb 18. Epub 2021 Feb 18.

Internal Medicine and Systemic Diseases, Hôpital François Mitterrand, CHU de Dijon, Dijon, France.

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http://dx.doi.org/10.1136/annrheumdis-2021-220037DOI Listing
February 2021

Dissemination of extreme levels of extracellular vesicles: tissue factor activity in patients with severe COVID-19.

Blood Adv 2021 02;5(3):628-634

Aix Marseille University, INSERM 1263, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), Centre de Recherche en CardioVasculaire et Nutrition (C2VN), Marseille, France.

Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century. Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis. Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events. Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218). The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P < .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters. High EV-TF values were associated with an increased thrombotic risk in multivariable models. Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1). Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease.
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http://dx.doi.org/10.1182/bloodadvances.2020003308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846479PMC
February 2021

Physician Global Assessment as a Disease Activity Measure for Relapsing Polychondritis.

Arthritis Care Res (Hoboken) 2021 Feb 5. Epub 2021 Feb 5.

Systemic Autoimmunity Branch, National Institutes of Health, NIAMS, Bethesda, MD, USA.

Objective: Relapsing polychondritis (RP) is a systemic inflammatory disorder of cartilage that lacks validated disease activity measures. Physician global assessment (PhGA), a measure of disease activity commonly used in rheumatologic diseases, has not been tested in a cohort of patients with RP.

Methods: Adult patients in an observational cohort of RP underwent standardized, comprehensive evaluation at approximately 6-month intervals. PhGA was scored by three physicians from the evaluating institution on a scale of 0 to 10 for each visit. A random subset of twenty visits was scored by three, independent physicians not affiliated with the evaluating institution. Treatment change between consecutive visits was categorized as increased, decreased or unchanged.

Results: 78 patients were evaluated over 164 visits. The interclass correlation coefficient (ICC) (2, 1) for the three raters from the evaluating institution was excellent (0.79, 95% CI: 0.73-0.84) but was poor in the subset of cases scored by the additional raters (ICC (2,1) = 0.27, 95% CI: -0.01-0.53). Median PhGA was 3 (range 0-7). PhGA weakly correlated with CRP (r = 0.30, p< 0.01). In response to increased treatment, median PhGA decreased from 3 (IQR: 2-4) to 2 (IQR: 2-3) (p< 0.01) but rarely went to 0.

Conclusion: Within a single-center, PhGA can be used to quantify disease activity and monitor disease response in RP. Persistent disease activity despite treatment, rather than a relapsing-remitting pattern, is observed for most patients with RP. Reliability of PhGA may not generalize across different institutions. A validated disease-specific activity index is needed in RP.
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http://dx.doi.org/10.1002/acr.24574DOI Listing
February 2021

Hydroxychloroquine in systemic and autoimmune diseases: Where are we now?

Joint Bone Spine 2021 05 28;88(3):105143. Epub 2021 Jan 28.

National reference centre for rare auto-immune and systemic diseases Est Sud-Est (RESO), 67000 Strasbourg, France; Department of rheumatology, hôpitaux universitaires de Strasbourg, 67098 Strasbourg, France; Université de Strasbourg, Inserm UMR-S 1109, 67000 Strasbourg, France. Electronic address:

Hydroxychloroquine (HCQ), one of the oldest drugs used in rheumatology, came recently into attention as one of the potential therapies tested for the severe acute respiratory syndrome coronavirus-2 disease treatment. Used initially as an antimalarial, then translated to rheumatic diseases, HCQ has been used in a wide range of pathologies, including infectious diseases, immune disorders, diabetes, dyslipidemia, or neoplasia. Regarding systemic diseases, HCQ is the mainstay treatment for systemic lupus erythematosus (SLE), where, according to last European guidelines, it is proposed to all SLE patients unless contraindicated or with side effects. HCQ proved positive impact in SLE on robust outcomes, such as accrual damage, disease activity and survival, but also pleiomorphic effects, including decrease in the need for glucocorticoids, reduction in the risk of neonatal lupus, lower fasting glucose and protection against diabetes, thrombotic risk, dyslipidemia, infections, etc. Moreover, HCQ can be used during pregnancy and breast-feeding. Besides SLE, the role for HCQ in the anti-phospholipid syndrome and Sjögren's disease is still under debate. On the contrary, recent advances showed only limited interest for rheumatoid arthritis, especially due the lack of structural damage prevention. There are still no strong data to sustain the HCQ use in other systemic diseases. In this review, we summarised the utility and efficacy of HCQ in different clinical conditions relevant for rheumatology practice.
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http://dx.doi.org/10.1016/j.jbspin.2021.105143DOI Listing
May 2021

Rheumatic presentations of Guillain-Barré syndrome as a diagnostic challenge: A case series.

Joint Bone Spine 2021 05 27;88(3):105144. Epub 2021 Jan 27.

Service de rhumatologie, Centre National de Référence des Maladies Auto-Immunes (RESO), Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France. Electronic address:

Background: Guillain-Barré syndrome (GBS) is an immune-mediated acute polyradiculoneuritis often in post-infectious context. It is a therapeutic emergency as early treatment may prevent disabilities. Pain in GBS has been described extensively, may precede neurological symptoms and bring the patient to rheumatology departments in the first place.

Objective: To describe the clinical presentations and diagnosis of GBS cases referred to rheumatology departments.

Method: For this retrospective case-series, we screened patients of the rheumatology department (university hospitals of Strasbourg), whose hospitalization records were associated with the ICD-10 Code G61.0 (GBS) from 1993 to 2020. We included patients fulfilling the 1990 NINDS criteria and level one of the Brighton collaboration criteria. We measured the time from symptoms onset to admission and from admission to lumbar puncture as a marker of outpatient and inpatient diagnosis delay, respectively.

Results: We describe 8 GBS cases. Six had nociceptive-like prodromal pain: back pain (n=3), peripheral arthralgia (n=1) or diffuse myalgia (n=3). The median time from symptoms onset to admission was 7days [range: 3-60] and the median time from admission to lumbar puncture was 2days [range: 0-8]. Two patients became severely tetraparetic, one requiring intubation. At last follow-up (median: 5.5years; range: 0.5-23years), 4 patients had recovered completely and 4 kept disabilities.

Conclusions: Rheumatic presentations of GBS are rare and diverse. Rheumatologists should be aware of this presentation because early diagnosis and treatment may prevent rapid motor worsening. Rapidly progressive symmetric weakness and areflexia appear as the best clinical diagnosis markers.
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http://dx.doi.org/10.1016/j.jbspin.2021.105144DOI Listing
May 2021

Atrial fibrillation in patients treated with intravenous zoledronic or pamidronic acid: a pharmacoepidemiological study.

Eur J Endocrinol 2021 Mar;184(3):437-444

Department of Rheumatology, Hôpitaux Universitaires de Strasbourg, Strasbourg University, Strasbourg, France.

Objective: Atrial fibrillation (AF) may be triggered by intravenous bisphosphonates (IVBPs) such as zoledronic acid or pamidronic acid. Our objective was to confirm the association between AF and IVBPs in a real-life large pharmacovigilance database.

Design: A systematic analysis of VigiBase, the World Health Organization's pharmacovigilance database.

Methods: Analysis of adverse events reported as 'atrial fibrillation' (according to the Medical Dictionary for Drug Regulatory Activities) associated with the use of zoledronic acid or pamidronic acid, in VigiBase, the World Health Organization's global Individual Case Safety Report (ICSR) database. All ICSRs reporting AF associated with zoledronic acid or pamidronic acid were included in a disproportionality analysis determining the lower end of the 95% credibility interval for the information component (IC025), showing a statistical association when >0.

Results: 530 ICSRs reporting on the association between AF and IVBPs were extracted. Bayesian disproportionality analysis detected a significant association between AF and use of zoledronic acid (IC025 = 1.83) and pamidronic acid (IC025 = 2.16). Further analysis of these ICSRs determined that AF was severe in 85.0% of cases and with a mortality of 17.7%. The risk of severe AF was increased (OR: 2.98 (95% CI: 1.17-7.57), P = 0.02) following zoledronic acid vs pamidronic acid, after adjustment for age and gender.

Conclusions: This is the first VigiBase pharmacoepidemiological study confirming the association between IVBPs and AF. Most AF were severe, with a high frequency of lethal outcome. The risk of severe AF was increased following zoledronic acid use compared to pamidronic acid, advocating for a cautious use of IVBPs.
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http://dx.doi.org/10.1530/EJE-20-0650DOI Listing
March 2021

The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

J Clin Med 2021 Jan 11;10(2). Epub 2021 Jan 11.

Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, 67000 Strasbourg, France.

Systemic lupus erythematosus (SLE) is an immune-mediated multi-systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Despite significant advances in the understanding of the pathophysiology and optimization of medical care, patients with SLE still have significant mortality and carry a risk of progressive organ damage accrual and reduced health-related quality of life. New tools allow earlier classification of SLE, whereas tailored early intervention and treatment strategies targeted to clinical remission or low disease activity could offer the opportunity to reduce damage, thus improving long-term outcomes. Nevertheless, the early diagnosis of SLE is still an unmet need for many patients. Further disentangling the SLE susceptibility and complex pathogenesis will allow to identify more accurate biomarkers and implement new ways to measure disease activity. This could represent a major step forward to find new trials modalities for developing new drugs, optimizing the use of currently available therapeutics and minimizing glucocorticoids. Preventing and treating comorbidities in SLE, improving the management of hard-to-treat manifestations including management of SLE during pregnancy are among the remaining major unmet needs. This review provides insights and a research agenda for the main challenges in SLE.
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http://dx.doi.org/10.3390/jcm10020243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827672PMC
January 2021

The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET.

Nat Rev Rheumatol 2021 03 6;17(3):177-184. Epub 2021 Jan 6.

Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.
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http://dx.doi.org/10.1038/s41584-020-00565-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786339PMC
March 2021

Shared development of targeted therapies among autoimmune and inflammatory diseases: a systematic repurposing analysis.

Ther Adv Musculoskelet Dis 2020 16;12:1759720X20969261. Epub 2020 Dec 16.

Service de rhumatologie, Centre National de Référence des Maladies Autoimmunes et Systémiques Rares, Hôpital de Hautepierre, 1 Avenue Molière BP 83049, Strasbourg Cedex, 67098, France.

Background: Pathogenic inflammatory pathways are largely shared between different autoimmune and inflammatory diseases (AIDs). This offers the potential to develop a given targeted therapy in several AIDs.

Methods: We analyzed two clinical trials registries (ClinicalTrials.gov and EU Clinical Trials Register) to identify the targeted therapies whose development is shared between at least two of the most common AIDs [rheumatoid arthritis (RA), spondyloarthritis (SpA), cutaneous psoriasis (cPso), inflammatory bowel diseases (IBD), systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), giant cell arteritis (GCA), and multiple sclerosis (MS)] using an in-depth repurposing analysis.

Results: We identified 142 shared targeted therapies. The four diseases in which shared targeted therapies were the most numerous were RA ( = 92), cPso ( = 67), IBD ( = 58), and SLE ( = 56). The two clusters of diseases between which the overlap of targeted therapies was the most important were RA and SLE as well as RA, SpA, cPso, and IBD. The targeted therapies which were shared by five diseases or more were abatacept, ustekinumab, rituximab, anakinra, etanercept, infliximab, secukinumab, tofacitinib, alemtuzumab, tocilizumab, adalimumab, apremilast, baricitinib, belimumab, brodalumab, filgotinib, and upadacitinib. The most frequently targeted molecules and pathways were (by descending frequency): JAK-STAT pathways, Th17 axis, TNF-α, IL-6, costimulation molecules, BAFF, CD20, BTK, chemokines and integrins, IL-1, and type I interferon.

Conclusion: Many targeted therapies are developed in several AIDs, reflecting the overlap of pathogenic pathways and potential of drug repurposing. This suggests that a revision of the current, clinically based classification of AIDs towards a more mechanistic-based taxonomy might be relevant.
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http://dx.doi.org/10.1177/1759720X20969261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747103PMC
December 2020

Immunosuppressive agents for rheumatoid arthritis: a systematic review of clinical trials and their current development stage.

Ther Adv Musculoskelet Dis 2020 16;12:1759720X20959971. Epub 2020 Dec 16.

Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Centre National de Référence des Maladies Autoimmunes et Systémiques Rares, Hôpital de Hautepierre, 1 Avenue Molière BP 83049, Strasbourg, Cedex, 67098, France.

Aims: With the arrival of conventional synthetic (csDMARDs), biological (bDMARDS) and then targeted synthetic (tsDMARDs) disease-modifying anti-rheumatic drugs, the therapeutic arsenal against rheumatoid arthritis (RA) has recently expanded. However, there are still some unmet needs for patients who do not achieve remission and continue to worsen despite treatments. Of note, most randomized controlled trials show that, for methotrexate-inadequate responders, only 20% of patients are ACR70 responders. With our better understanding of RA pathogenesis, finding new treatments is a necessary challenge. The objective of our study was to analyse the whole pipeline of immunosuppressive and immunomodulating drugs evaluated in RA and describe their mechanisms of action and stage of clinical development.

Methods: We conducted a systematic review of all drugs in clinical development in RA, in 17 online registries of clinical trials.

Results: The search yielded 4652 trials, from which we identified 243 molecules. Those molecules belong to csDMARDs ( = 22), bDMARDs ( = 118), tsDMARDs ( = 103). Twenty-four molecules are already marketed in RA in at least one country: eight csDMARDs, 10 bDMARDs and six tsDMARDs. Molecules under current development are mainly bDMARDs ( = 34) and tsDMARDs ( = 33). Seven of those have reached phase III. A large number of molecules (150/243, 61.7%) have been withdrawn.

Conclusion: Despite the availability of 24 marketed molecules, the development of new targeted molecules is ongoing with a total of 243 molecules in RA. With seven molecules currently reaching phase III, we can expect an increase in the armamentarium in the years to come.
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http://dx.doi.org/10.1177/1759720X20959971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747097PMC
December 2020

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
June 2021

Systemic sclerosis overlap and non-overlap syndromes share clinical characteristics but differ in prognosis and treatments.

Semin Arthritis Rheum 2021 02 18;51(1):36-42. Epub 2020 Dec 18.

Centre Hospitalier Universitaire de Bordeaux, FHU ACRONIM, Place Amélie Raba Léon, 33076 Bordeaux, France; Centre national de référence des maladies auto-immunes et systémiques rares Est/Sud-Ouest (RESO), France; CNRS-UMR 5164 Immuno ConcEpT, 146 rue Léo Saignat, 33076 Bordeaux, France. Electronic address:

Objectives: To screen for concomitant autoimmune disease in patients with systemic sclerosis (overlap SSc) and to describe their clinical characteristics and prognosis.

Methods: This was a two-center retrospective observational study. Patients diagnosed with SSc according to the 2013 ACR-EULAR scleroderma classification criteria were screened for concomitant rheumatoid arthritis (RA), Sjögren syndrome (SgS) and systemic lupus erythematosus (SLE). Patient characteristics were retrieved from the medical records and were compared to those of a non-overlap SSc cohort.

Results: Among the 534 SSc patients studied, thirty-four (6.4%) were identified as having overlap SSc. There were 21 (3.9%) patients with RA, 14 (2.6%) with SgS and 4 (0.7%) with SLE (5 patients had 2 AISD) . The disease phenotype of overlap SSc was similar to that of non-overlap SSc in terms of cutaneous phenotype, prevalence of pulmonary arterial hypertension, interstitial lung disease, digital ulcers and mortality. Using a multivariate Cox model, age (HR = 1.04, 95% CI [1.02-1.07]), the modified Rodnan skin score (HR = 1.08 per point, 95% CI [1.05-1.11]), and the presence of concomitant SgS (HR = 3.79, 95% CI [1.38-10.40]) were significantly associated with mortality. Overlap SSc were more likely to receive corticosteroids (85.3% vs. 45%, p < 0.001), immunosuppressive drugs (82.4% vs. 49.2%, p < 0.001) and biologics (52.9% vs. 3.8%, p < ZZ0.001).

Conclusions: While overlap and non-overlap SSc shared common characteristics, patients with SgS/SSc had a higher risk of mortality, and those with RA/SSc received more corticosteroids, methotrexate and biologics. Screening for an associated AISD should be promoted since their co-occurrence with SSc may affect prognosis and treatments.
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http://dx.doi.org/10.1016/j.semarthrit.2020.10.009DOI Listing
February 2021

Long-term outcomes in systemic lupus erythematosus: trends over time and major contributors.

Rheumatology (Oxford) 2020 12;59(Suppl5):v29-v38

Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Joint Rheumatology Program, Laiko Hospital, Athens, Greece.

SLE is a chronic autoimmune rheumatic disorder of high heterogeneity in clinical presentation, treatment response and prognosis. Long-term outcomes in SLE have been dramatically improved over the past decades, however, increased morbidity and mortality, especially among young individuals, still exists. Unmet needs include residual disease activity and frequent flares, glucocorticoid treatment dependency and toxicity, comorbidity burden, reduced health-related quality of life, health disparities and damage. The main determinants of long-term outcomes in SLE are age, sex, race/ethnicity, genetic profile, environmental factors including smoking, disease activity, major organ involvement such as lupus nephritis and CNS involvement, comorbidities including cardiovascular disease and serious infections, coexistence with APS, treatment adherence, socio-economic factors and access to care. In this review we discuss trends in long-term outcomes in SLE over the years and major contributors such as genetic, disease-related, treatment, comorbidity, socio-economic and other factors.
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http://dx.doi.org/10.1093/rheumatology/keaa382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719040PMC
December 2020

Venous thromboembolism in anti-neutrophil cytoplasmic antibody-associated vasculitis: an underlying prothrombotic condition?

Rheumatol Adv Pract 2020 16;4(2):rkaa056. Epub 2020 Oct 16.

Department of Medicine, Division of Rheumatology, Karolinska Institutet.

Objectives: We investigated the incidence and potential underlying risk factors of venous thromboembolism (VTE) in patients with AAV. We assessed haemostatic disturbances and factors that might contribute to the risk of development of VTE.

Methods: ANCA-positive AAV patients ( = 187) were included. Previously identified risk factors for VTE and current medication were retrieved from the medical records. We assessed haemostasis using different methods [endogenous thrombin potential (ETP), overall haemostatic potential (OHP), overall coagulation potential (OCP) and overall fibrinolysis potential (OFP)] in patients with active AAV ( = 19), inactive AAV ( = 15) and healthy controls ( = 15).

Results: Twenty-eight VTEs occurred in 24 patients over a total follow-up time of 1020 person-years. A majority of VTEs occurred within the first year after diagnosis. Old age ( < 0.01), ongoing prednisolone treatment and recent rituximab administration were more common in the VTE group ( < 0.05 for all). ETP and OHP were significantly increased and OFP significantly decreased in plasma from active compared with inactive AAV patients ( < 0.05,  < 0.01 and  < 0.05, respectively) and healthy controls ( < 0.001). We could not confirm previously reported risk factors for VTE development.

Conclusion: A high prevalence of VTE in AAV patients was seen within the first year after diagnosis, suggesting that disease activity contributes to development of VTE. Old age and concurrent treatment should also be taken into account when estimating VTE risk. The results also indicate disturbances in the haemostatic balance towards pro-thrombotic conditions in AAV patients, where ETP and OHP might be useful markers for identifying patients at high risk.
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http://dx.doi.org/10.1093/rap/rkaa056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661844PMC
October 2020

Towards a practical management of fatigue in systemic lupus erythematosus.

Lupus Sci Med 2020 11;7(1)

Department of Rheumatology, Hôpitaux universitaires de Strasbourg, Strasbourg, France

Significant fatigue is reported by two-thirds of patients with SLE and severe fatigue by one-third. The assessment and treatment of fatigue remains a major challenge in SLE, especially in patients with no disease activity. Here, we suggest a practical algorithm for the management of fatigue in SLE. First, common but non-SLE-related causes of fatigue should be ruled out based on medical history, clinical and laboratory examinations. Then, presence of SLE-related disease activity or organ damage should be assessed. In patients with active disease, remission is the most appropriate therapeutic target while symptomatic support is needed in case of damage. Both anxiety and depression are major independent predictors of fatigue in SLE and require dedicated assessment and care with psychological counselling and pharmacological intervention if needed. This practical algorithm will help in improving the management of one the most common and complex patient complaints in SLE.
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http://dx.doi.org/10.1136/lupus-2020-000441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678390PMC
November 2020
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