Publications by authors named "Laura Andreoli"

139 Publications

Maternal, pregnancy and neonatal outcomes of twin gestations in women with rheumatic diseases: A single-center, case-control study.

Eur J Obstet Gynecol Reprod Biol 2021 Jun 29;264:49-55. Epub 2021 Jun 29.

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Department of Obstetrics and Gynecology, ASST Spedali Civili, Brescia, Italy. Electronic address:

Objective: To assess maternal, pregnancy and neonatal outcomes of twin pregnancy (TP) in women with rheumatic diseases (RD) (Group A) as compared to those of singleton pregnancy (SP) in women with RD (Group B) and TP in the general obstetric population (GOP) (Group C).

Methods: Case-control study including TP in RD during the period 2009-2020 at single institution. Women in Group A were matched with women of the same age at conception and affected by the same RD (Group B). Women in Group A and C were also matched.

Results: Fifty-three women with RD (13 in Group A and 40 in Group B) and 39 healthy controls were included. RD was quiescent in 85% of patients in both Groups A and B. Spontaneous conception was more frequent in Group B (98%), as compared to A (62%) (p = 0.002). Emergency cesarean section and premature delivery were more frequent in Group A as compared to B and C (54% vs 15% vs 23%, p = 0.008, 69% vs 13% vs 39%, p < 0.000 and p = 0.054, respectively). Five babies (21%) in Group A required admission to the neonatal intensive care unit (NICU), but none in Group B (p = 0.007).

Conclusion: This is the first case-control study assessing the outcomes of TP in women with RD. An increased risk of preterm delivery, emergency cesarean section and admission to NICU as compared to both SP in RD and TP in the GOP was observed. Multidisciplinary management is warranted to minimize these risks.
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http://dx.doi.org/10.1016/j.ejogrb.2021.06.043DOI Listing
June 2021

Low Preconception Complement Levels Are Associated with Adverse Pregnancy Outcomes in a Multicenter Study of 260 Pregnancies in 197 Women with Antiphospholipid Syndrome or Carriers of Antiphospholipid Antibodies.

Biomedicines 2021 Jun 11;9(6). Epub 2021 Jun 11.

Lupus Clinic, Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, 00185 Rome, Italy.

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers' pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed ( = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss ( = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.
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http://dx.doi.org/10.3390/biomedicines9060671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230784PMC
June 2021

Quality indicators for systemic lupus erythematosus based on the 2019 EULAR recommendations: development and initial validation in a cohort of 220 patients.

Ann Rheum Dis 2021 Jun 23. Epub 2021 Jun 23.

Rheumatology and Clinical Immunology, Medical School, National and Kapodistrian University of Athens, "Attikon" University Hospital of Athens, Athens, Greece

Background: Quality of care is receiving increased attention in systemic lupus erythematosus (SLE). We developed quality indicators (QIs) for SLE based on the 2019 update of European League Against Rheumatism recommendations.

Methods: A total of 44 candidate QIs corresponding to diagnosis, monitoring and treatment, were independently rated for validity and feasibility by 12 experts and analysed by a modified Research and Development Corporation/University of California Los Angeles model. Adherence to the final set of QIs and correlation with disease outcomes (flares, hospitalisations and organ damage) was tested in a cohort of 220 SLE patients with a median monitoring of 2 years (IQR 2-4).

Results: The panel selected a total of 18 QIs as valid and feasible. On average, SLE patients received 54% (95% CI 52.3% to 56.2%) of recommended care, with adherence ranging from 44.7% (95% CI 40.8% to 48.6%) for diagnosis-related QIs to 84.3% (95% CI 80.6% to 87.5%) for treatment-related QIs. Sustained remission or low disease activity were achieved in 26.8% (95% CI 21.1% to 33.2%). Tapering of prednisone dose to less than 7.5 mg/day was achieved in 93.6% (95% CI 88.2% to 97.0%) while 73.5% (95% CI 66.6% to 79.6%) received the recommended hydroxychloroquine dose. Higher adherence to monitoring-related QIs was associated with reduced risk for a composite adverse outcome (flare, hospitalisation or damage accrual) during the last year of observation (OR 0.97 per 1% adherence rate, 95% CI 0.96 to 0.99).

Conclusion: We developed QIs for assessing and improving the care of SLE patients. Initial real-life data suggest face validity, but a variable degree of adherence and a need for further improvement.
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http://dx.doi.org/10.1136/annrheumdis-2021-220438DOI Listing
June 2021

Distinct patterns of dyskinetic and dystonic features following D1 or D2 receptor stimulation in a mouse model of parkinsonism.

Neurobiol Dis 2021 Jun 19;157:105429. Epub 2021 Jun 19.

Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, BMC, 221 84 Lund, Sweden. Electronic address:

L-DOPA-induced dyskinesia (LID) is a significant complication of dopamine replacement therapy in Parkinson's disease (PD), and the specific role of different dopamine receptors in this disorder is poorly understood. We set out to compare patterns of dyskinetic behaviours induced by the systemic administration of L-DOPA and D1 or D2 receptor (D1R, D2R) agonists in mice with unilateral 6-hydroxydopamine lesions. Mice were divided in four groups to receive increasing doses of L-DOPA, a D1R agonist (SKF38393), a D2/3 agonist (quinpirole), or a selective D2R agonist (sumanirole). Axial, limb and orofacial abnormal involuntary movements (AIMs) were rated using a well-established method, while dystonic features were quantified in different body segments using a new rating scale. Measures of abnormal limb and trunk posturing were extracted from high-speed videos using a software for markerless pose estimation (DeepLabCut). While L-DOPA induced the full spectrum of dyskinesias already described in this mouse model, SKF38393 induced mostly orofacial and limb AIMs. By contrast, both of the D2-class agonists (quinpirole, sumanirole) induced predominantly axial AIMs. Dystonia ratings revealed that these agonists elicited marked dystonic features in trunk/neck, forelimbs, and hindlimbs, which were overall more severe in sumanirole-treated mice. Accordingly, sumanirole induced pronounced axial bending and hindlimb divergence in the automated video analysis. In animals treated with SKF38393, the only appreciable dystonic-like reaction consisted in sustained tail dorsiflexion and stiffness. We next compared the effects of D1R or D2R selective antagonists in L-DOPA-treated mice, where only the D2R antagonist had a significant effect on dystonic features. Taken together these results indicate that the dystonic components of LID are predominantly mediated by the D2R.
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http://dx.doi.org/10.1016/j.nbd.2021.105429DOI Listing
June 2021

Characterization of B- and T-Cell Compartment and B-Cell Related Factors Belonging to the TNF/TNFR Superfamily in Patients With Clinically Active Systemic Lupus Erythematosus: Baseline BAFF Serum Levels Are the Strongest Predictor of Response to Belimumab after Twelve Months of Therapy.

Front Pharmacol 2021 21;12:666971. Epub 2021 May 21.

Department of Rheumatology and Hiller Research Center for Rheumatology, University Hospital Düsseldorf, Düsseldorf, Germany.

Patients with systemic lupus erythematosus (SLE) show increased serum levels of tumor necrosis factor (TNF)/TNF receptor (R) superfamily member, e.g. BAFF (B lymphocyte stimulator). Belimumab, a monoclonal antibody against soluble BAFF, is used for treatment of SLE. Although B cells are the main target, a BAFF-dependent T-cell activation pathway also plays a role. High levels of anti-DNA antibodies and low complement at baseline are known predictors of response to Belimumab. To explore the association of circulating lymphocytes and serum levels of B- cell related TNF/TNFR superfamily members with response to Belimumab in SLE patients. Twenty-one SLE patients received Belimumab. Clinical evaluation and laboratory tests were performed at baseline, at 6 and 12 months. TNF super-family members (BAFF, APRIL, sBCMA, sCD40L, sTACI, TWEAK) were tested by high-sensitivity ELISA in all patients, and lymphocyte immunophenotyping was performed by flow cytometry in ten subjects. SLE-disease activity was assessed by SLEDAI-2K score. Linear regression modeling was used to investigate parameters influencing SLEDAI-2K and anti-dsDNA antibody titers over time and for predictive models. Clinical improvement was observed in all patients. A global reduction of circulating B cells, especially naïve, was detected, without variation in the T-cell compartment. All TNF family members decreased, whereas APRIL remained constant. The increase in serum levels of C3 ( = 0.0004) and sTACI ( = 0.0285) was associated with a decrease of SLEDAI-2K. The increase of C4 ( = 0.027) and sBCMA ( = 0.0015) and the increase of CD8 T cells ( = 0.0160) were associated with a decrease, whereas an increase of sCD40L in serum ( = 0.0018) and increased number of CD4 T cells ( = 0.0029) were associated with an increase, in anti-dsDNA antibody titers, respectively. Using stepwise forward inclusion, the minimal model to predict SLEDAI-2K response at 12 months included BAFF ( = 3.0 - 07) and SLEDAI-2K ( = 7.0 - 04) at baseline. Baseline APRIL levels also showed an association, although the overall model fit was weaker. In our real-life cohort, baseline serum levels of BAFF were the best predictor of response to Belimumab, confirming post-hoc results of the BLISS study and suggesting the utility of this particular biomarker for the identification of patients who are more likely to respond.
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http://dx.doi.org/10.3389/fphar.2021.666971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176088PMC
May 2021

The Influence of Treatment of Inflammatory Arthritis During Pregnancy on the Long-Term Children's Outcome.

Front Pharmacol 2021 18;12:626258. Epub 2021 Mar 18.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili and University of Brescia, Brescia, Italy.

The management of reproductive issues in women with inflammatory arthritis has greatly changed over decades. In the 1980-1990s, women with refractory forms of arthritis were either not able to get pregnant or did choose not to get pregnant because of their disabling disease. Hence, the traditional belief that pregnancy can induce a remission of arthritis. The availability of biologic agents has allowed a good control of aggressive forms of arthritis. The main topic of discussion during preconception counselling is the use of drugs during pregnancy and breastfeeding. Physicians are now supported by international recommendations released by the European League Against Rheumatism and the American College of Rheumatology, but still they must face with cultural reluctance in accepting that a pregnant woman can take medications. Patient-physician communication should be centered on the message that active maternal disease during pregnancy is detrimental to fetal health. Keeping maternal disease under control with drugs which are not harmful to the fetus is the best way to ensure the best possible outcome for both the mother and the baby. However, there might be concerns about the influence of the exposure to medications on the newborn's health conditions. Particularly, studies suggesting an increased risk of autism-spectrum-disorders in children born to women with rheumatoid arthritis has raised questions about neuropsychological impairment in the offspring of women with chronic arthritis. As a multidisciplinary group of rheumatologists and child neuropsychiatrists, we conducted a study on 16 women with chronic forms of arthritis whose diagnosis was determined before pregnancy and their 18 school-age children. The children underwent a complete neurological examination and validated tests/questionnaires. Behavioral aspects of somatization and anxiety/depression (internalizing problem) or an "adult profile" were found in nearly one third of children. Children at a high risk of neurodevelopmental problems were born to mothers with a longer history of arthritis and were breastfeed for less than 6 months of age or were not breastfeed at all. No association was found with other maternal characteristics such as autoantibody existence and disease activity during and after the pregnancy.
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http://dx.doi.org/10.3389/fphar.2021.626258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013697PMC
March 2021

Long-term Outcome of Children Born to Women with Autoimmune Rheumatic Diseases: A Multicentre, Nationwide Study on 299 Randomly Selected Individuals.

Clin Rev Allergy Immunol 2021 Mar 16. Epub 2021 Mar 16.

Department of Medicine, Rheumatology Unit, University of Perugia, Piazzale Gambuli 1, 06132, Perugia, Italy.

The concern about the offspring's health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.
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http://dx.doi.org/10.1007/s12016-021-08857-2DOI Listing
March 2021

Safety considerations when using drugs in pregnant patients with systemic lupus erythematosus.

Expert Opin Drug Saf 2021 May 8;20(5):523-536. Epub 2021 Mar 8.

Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

: Systemic lupus erythematosus (SLE) mainly affects young females during childbearing age; therefore, reproductive issues are of major interest.: Pregnancy planning is crucial to adjust the treatment toward drugs that are safe throughout pregnancy and breastfeeding. The evidence about drug safety is limited to post-marketing surveillance, registries, case series, and case reports, as pregnant patients are excluded from randomized clinical trials. The aim of this review is to report the safety considerations when treating pregnant SLE patients. Regarding maternal side effects of drugs, we focused on metabolic, infectious, and hemorrhagic complications. Fetal safety was analyzed looking at drugs teratogenicity, their possible effects on immune system, and on the long-term neuropsychological development of children.: The management of pregnancy in SLE has changed when knowledge about the safety of drugs has become available. Keeping SLE disease activity under control before, during and after pregnancy is of fundamental importance to ensure the best possible outcomes for mother and child. All these issues must be discussed with the patient and her family during preconception counseling. International efforts in terms of pregnancy registries and reproductive health guidelines help physicians improve their communication with SLE patients.
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http://dx.doi.org/10.1080/14740338.2021.1893298DOI Listing
May 2021

Are remission and low disease activity state ideal targets for pregnancy planning in Systemic Lupus Erythematosus? A multicentre study.

Rheumatology (Oxford) 2021 Feb 16. Epub 2021 Feb 16.

Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.

Objectives: To determine whether disease remission or low disease activity state at the beginning of pregnancy in SLE patients is associated with better pregnancy outcome.

Methods: pregnancies in SLE patients prospectively monitored by pregnancy clinics at four rheumatology centres were enrolled. Patient demographics and clinical information were collected at baseline (pregnancy visit before 8 weeks of gestation) including whether patients were in remission according to DORIS criteria and and/or Lupus Low Disease Activity State (LLDAS). Univariate and multivariate analysis were performed to determine predictors of disease flare and adverse pregnancy outcomes (APOs) including preeclampsia, preterm delivery, small for gestational age infant, intrauterine growth restriction and intrauterine fetal death.

Results: 347 pregnancies were observed in 281 SLE patients. Excluding early pregnancy losses, 212 pregnancies (69.7%) occurred in patients who were in remission at baseline, 33 (10.9%) in patients in LLDAS, and the remainder in active patients. 73 flares (24%) were observed during pregnancy or puerperium, and 105 (34.5%) APOs occurred. Multivariate analysis revealed that patients in disease remission or taking hydroxychloroquine were less likely to have disease flare, while a history of lupus nephritis increased the risk. The risk of APOs was increased in patients with shorter disease duration, while being on hydroxychloroquine resulted a protective variable. An almost significant association between complete remission and a decreased risk of APOs was observed.

Conclusions: Prenatal planning with a firm treat-to-target goal of disease remission is an important strategy to reduce the risk of disease flares and severe obstetrical complications in SLE pregnancies.
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http://dx.doi.org/10.1093/rheumatology/keab155DOI Listing
February 2021

Neuropsychiatric Outcome of Children Born to Women With Systemic Lupus Erythematosus and Exposed to Azathioprine: A Case-Control Study.

Front Pharmacol 2020 16;11:613239. Epub 2020 Dec 16.

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

The long-term outcome of children born to SLE mothers still represents a controversial topic in literature, with some studies reporting a possible increased prevalence of different neurologic and psychiatric diseases (NPD), including neurodevelopmental disorders (ND), and in particular learning disorders (LD). Different risk factors have been advocated, such as the exposure to auto-antibodies and drugs, particularly Azathioprine (AZA). A case-control study was designed to compare pregnancies treated with AZA (cases) with those not treated with AZA (controls). All the pregnancies had been prospectively followed in two Italian centers. The match was based upon renal involvement, antiphospholipid (aPL) status, maternal age at pregnancy (±5 years) and child's age at the time of the study (±2 years). SLE mothers were interviewed by a telephone survey, particularly focused on the presence of a certified NPD in their children ≥6 years of age. Twenty-seven cases and 65 controls were similar in terms of demographic, immunological and clinical features, except for a higher rate of SLE flares during pregnancy in cases (22.2% vs. 10.8%, :0.191). The 92 children had a mean age of 14.0 years at the time of the survey; 11 had at least one NPD (12.0%). The frequency of each single NPD was similar to that of the general pediatric population and no association was found with either the exposure to AZA, or other specific factors (auto-antibodies, disease activity, obstetric complications, prematurity). The long-term neuropsychiatric outcome of the children born to SLE mothers did not show neither an increased frequency of NPD as compared to the general pediatric population nor a specific pattern of NPD. The exposure to AZA was not associated with the development of NPD in this case-control study of prospectively-followed pregnancies. NPD are complex conditions and large prospective studies are needed to capture the wide range of variables that may contribute to their development in the offspring of SLE women.
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http://dx.doi.org/10.3389/fphar.2020.613239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772243PMC
December 2020

Anti-Phospholipid Antibodies in COVID-19 Are Different From Those Detectable in the Anti-Phospholipid Syndrome.

Front Immunol 2020 15;11:584241. Epub 2020 Oct 15.

Immunorheumatology Research Laboratory, Istituto Auxologico Italiano, Istituto di Ricovero Cura a Carattere Scientifico (IRCCS), Milan, Italy.

Background: Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPLs) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-βGPI), and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-βGPI antibodies was not reported.

Objective: To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-βGPI antibodies.

Methods: ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events.

Results: Anti-βGPI IgG/IgA/IgM was the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM was detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of βGPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-βGPI nor with thrombosis.

Conclusions: aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against βGPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.
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http://dx.doi.org/10.3389/fimmu.2020.584241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593765PMC
December 2020

Trial of Rivaroxaban in AntiPhospholipid Syndrome (TRAPS): Two-year outcomes after the study closure.

J Thromb Haemost 2021 02 29;19(2):531-535. Epub 2020 Nov 29.

Thrombosis Research Laboratory, Department of Cardiac Thoracic and Vascular Sciences, and Public Health, University of Padova, Padova, Italy.

Background: Trial of Rivaroxaban in AntiPhospholipid Syndrome was a prospective randomized, open-label, noninferiority study conducted in 14 centers in Italy. Rivaroxaban was compared with warfarin for the prevention of thromboembolic events, major bleeding, and vascular death in high-risk, triple-positive patients with antiphospholipid syndrome.

Objective: The aim of this paper is to report the events during the 2-year follow-up after the study closure.

Methods: On January 28, 2018, the trial was prematurely stopped by adjudication and safety committee for an excess of events in the rivaroxaban group. Randomized patients were advised on trial results and those randomized to rivaroxaban were solicited to switch to warfarin. All 14 participating centers were asked and accepted to follow their patients for clinical events. This report describes the rate of events that occurred between January 28, 2018, and January 28, 2020.

Results: Of 120 randomized patients, 115 were available for follow-up. Outcome events were two in six (33.3%) patients who remained on direct oral anticoagulants (DOACs) and six in 109 (5.7%) patients on warfarin (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.4-34.5, P = .018). The two patients on DOACs (one taking dabigatran and one taking rivaroxaban) suffered from thromboembolic events, whereas of the six patients with composite outcomes on warfarin, three had thromboembolic events (HR for thrombosis 13.3; 95% CI 2.2-79.9, P = .005).

Conclusion: These data further support the use of warfarin in high-risk patients with antiphospholipid syndrome.
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http://dx.doi.org/10.1111/jth.15158DOI Listing
February 2021

Epigenetics, pregnancy and autoimmune rheumatic diseases.

Autoimmun Rev 2020 Dec 22;19(12):102685. Epub 2020 Oct 22.

Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS San Martino Polyclinic Hospital, Genova, Italy. Electronic address:

Autoimmune rheumatic diseases (ARDs) are chronic conditions with a striking female predominance, frequently affecting women of childbearing age. Sex hormones and gender dimorphism of immune response are major determinants in the multifactorial pathogenesis of ARDs, with significant implications throughout reproductive life. Particularly, pregnancy represents a challenging condition in the context of autoimmunity, baring profound hormonal and immunologic changes, which are responsible for the bi-directional interaction between ARDs outcome and pregnancy course. In the latest years epigenetics has proven to be an important player in ARDs pathogenesis, finely modulating major immune functions and variably tuning the significant gender effects in autoimmunity. Additionally, epigenetics is a recognised influencer of the physiological dynamic modifications occurring during pregnancy. Still, there is currently little evidence on the pregnancy-related epigenetic modulation of immune response in ARDs patients. This review aims to overview the current knowledge of the role of epigenetics in the context of autoimmunity, as well as during physiologic and pathologic pregnancy, discussing under-regarded aspects in the interplay between ARDs and pregnancy pathology. The outline of a new ongoing European project will be presented.
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http://dx.doi.org/10.1016/j.autrev.2020.102685DOI Listing
December 2020

EULAR recommendations for a core data set for pregnancy registries in rheumatology.

Ann Rheum Dis 2021 01 14;80(1):49-56. Epub 2020 Oct 14.

Epidemiology and Health Care Research, German Rheumatism Research Center Berlin, Berlin, Germany.

Background And Objective: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD.

Methods: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items.

Results: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering 'maternal information', 'pregnancy' and 'treatment'. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed.

Conclusion: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy.
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http://dx.doi.org/10.1136/annrheumdis-2020-218356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788063PMC
January 2021

Classical Examples of the Concept of the ASIA Syndrome.

Biomolecules 2020 10 12;10(10). Epub 2020 Oct 12.

Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5265601, Israel.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren's syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.
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http://dx.doi.org/10.3390/biom10101436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600067PMC
October 2020

Characteristics of Antiphospholipid Antibody Positive Patients in AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking.

Arthritis Care Res (Hoboken) 2020 Sep 28. Epub 2020 Sep 28.

Barbara Volcker Center for Women and Rheumatic Disease, Hospital For Special Surgery, Weill Cornell Medicine, New York, NY, USA.

Objective: To describe baseline characteristics of antiphospholipid antibody (aPL)-positive patients, overall and by clinical and laboratory subtypes, enrolled in an international registry.

Methods: AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Registry includes persistently aPL-positive adults. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS [TAPS] only, obstetric APS [OAPS] only, and both TAPS/OAPS). We assessed baseline characteristics of patients tested for three aPL (lupus anticoagulant test [LA], anticardiolipin antibody [aCL], and anti-β -Glycoprotein-I [aβ GPI]) by aPL profiles (LA only, single, double, and triple aPL positivity).

Results: Of 804 aPL-positive patients (mean age: 45 ± 13y; female: 74%; white 68%; other systemic autoimmune diseases: 36%), 80% were classified as APS (55% TAPS, 9% OAPS, and 15% TAPS/OAPS). In the overall cohort, 71% had vascular thrombosis, 50% with pregnancy history had obstetric morbidity, and 56% had at least one non-criteria manifestation. Among those with three aPL tested (n: 660), 42% were triple aPL positive. While single, double and triple aPL positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup consisting of aCL or aβ GPI only.

Conclusion: Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter, international cohort. Within single aPL-positivity, LA may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.
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http://dx.doi.org/10.1002/acr.24468DOI Listing
September 2020

Disease course and obstetric outcomes of pregnancies in juvenile idiopathic arthritis: are there any differences among disease subtypes? A single-centre retrospective study of prospectively followed pregnancies in a dedicated pregnancy clinic.

Clin Rheumatol 2021 Jan 18;40(1):239-244. Epub 2020 Sep 18.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, Brescia, Italy.

To study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery. Key Points • In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy. • Flares were observed only in PLA and OLA-E patients. • Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy.
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http://dx.doi.org/10.1007/s10067-020-05404-wDOI Listing
January 2021

Psychosocial burden in young patients with primary anti-phospholipid syndrome: an Italian nationwide survey (The AQUEOUS study).

Clin Exp Rheumatol 2020 Sep 16. Epub 2020 Sep 16.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, Department of Clinical and Experimental Sciences, University of Brescia, Italy.

Objectives: The AQUEOUS (Anti-phospholipid syndrome: a QUEstionnaire for yOUng patientS) study aimed to assess how the diagnosis of primary anti-phospholipid syndrome (PAPS) affects the psychosocial status of young patients.

Methods: Subjects with PAPS aged 18-45 years were invited to compile an ad hoc designed questionnaire and the Short Form-12 to assess quality of life (QoL).

Results: Ninety-two patients (83.7% females) were recruited in 10 Italian centres. Vascular and obstetric manifestations were equally represented. Nearly half of the patients perceived the need for psychological support, 89.2% when considering women after pregnancy complications. Social activities and working efficiency were reduced in APS patients, also intimacy was threatened. In all cases, fatigue appeared to be the main determinant. PAPS affected family planning, due to fears of treatment side-effects, disease hereditariness, inability to care for the newborn child. Fertility appeared to be conserved: the median time to pregnancy was 2 months; assisted reproduction techniques were pursued by 5 women. Our survey documented significantly lower rates of hospitalisation and learning disabilities in 51 children born after APS diagnosis as compared to 48 children born before. PAPS patients displayed lower QoL in physical and, to a greater extent, mental scores compared to the general Italian population. Both components were significantly lower in women and in patients with fatigue.

Conclusions: The AQUEOUS study assessed for the first time the unmet needs of young PAPS patients, enabling the development of a future "youth-focused" strategy to reduce disease burden.
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September 2020

Coagulation dysfunction in COVID-19: The interplay between inflammation, viral infection and the coagulation system.

Blood Rev 2021 03 24;46:100745. Epub 2020 Aug 24.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. Electronic address:

COVID-19 is a new pandemic, caused by Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-Cov2) infection and characterized by a broad spectrum of clinical manifestations. Inflammation and the innate immune system have been recently recognized as pivotal players in the most severe forms, characterized by significantly elevated levels of pro-inflammatory cytokines. In this setting, several studies have also reported the presence of abnormalities in coagulation parameters and platelets count, possibly identifying a subgroup of patients with poor prognosis. Some reports of full-blown thromboembolic events are emerging. Among the possible mechanisms underlying coagulation dysfunction, the so-called "cytokine storm" seems to play a pivotal role. Other candidate factors include virus-specific mechanisms, related to the virus interaction with renin angiotensin system (RAS) and the fibrinolytic pathway, but also comorbidities affecting these patients. Coagulation dysfunction is therefore a candidate risk factor for adverse outcomes in COVID-19 and should be carefully addressed in clinical practice.
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http://dx.doi.org/10.1016/j.blre.2020.100745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444609PMC
March 2021

COVID-19 in patients with rheumatic diseases in northern Italy: a single-centre observational and case-control study.

Lancet Rheumatol 2020 Sep 18;2(9):e549-e556. Epub 2020 Jun 18.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia, Brescia, Italy.

Background: The highest number of COVID-19 cases in Italy have been reported in Lombardy, a region in northern Italy. We aimed to analyse the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic and musculoskeletal diseases living in a district of Lombardy with a high prevalence of COVID-19.

Methods: We did a single-centre observational study at the Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili of Brescia, Italy. We collected data from patients with rheumatic and musculoskeletal diseases enrolled in our outpatient clinic to identify confirmed or possible cases of SARS-CoV-2 infection. Data were collected through a survey that was administered via telephone or in the outpatient clinic by rheumatologists. We also did a case-control study of all patients with confirmed COVID-19 pneumonia and rheumatic and musculoskeletal diseases who were admitted to the ASST Spedali Civili of Brescia during the study period. Cases were matched by age, sex, and month of hospital admission to at least two controls admitted to the same hospital for COVID-19 pneumonia during the study period.

Findings: Between Feb 24 and May 1, 2020, we collected data from 1525 patients with rheumatic and musculoskeletal diseases: 117 (8%) presented with symptoms that were compatible with COVID-19. 65 patients had a swab confirmation of SARS-CoV-2 infection, whereas 52 presented with a spectrum of symptoms indicative of COVID-19 but were not swab tested. Patients with confirmed COVID-19 were older than those with suspected COVID-19 (median age 68 [IQR 55-76] years 57 [49-67] years; p=0·0010) and more likely to have arterial hypertension (33 [51%] 14 [27%] patients; odds ratio [OR] 2·8 [95% CI 1·3-6·1]; p=0·031) and obesity (11 [17%] 1 [2%]; OR 11·0 [1·3-83·4]; p=0·0059). We found no differences in rheumatological disease or background therapy between confirmed and suspected COVID-19 cases. 47 (72%) of the 65 patients with confirmed COVID-19 developed pneumonia that required admission to hospital. 12 (10%) deaths occurred among the 117 patients with confirmed or suspected COVID-19 (ten in those with confirmed COVID-19 and two in those with suspected COVID-19). Deceased patients with confirmed COVID-19 were older than survivors (median age 78·8 years [IQR 75·3-81·3] 65·5 years [53·3-74·0]; p=0·0002). We observed no differences in sex, comorbidities, or therapies between the deceased patients and survivors. The case-control study comprised 26 patients with rheumatic and musculoskeletal diseases and COVID-19 pneumonia and 62 matched controls. We found no significant differences between cases and controls in duration of COVID-19 symptoms before admission, duration of stay in hospital, or the local chest X-ray scoring system. Glucocorticoids were used for severe respiratory manifestations related to lung involvement in 17 (65%) of 26 cases and tocilizumab in six (23%) of 26; thrombotic events occurred in four (15%) of 26 cases. Four (15%) of 26 cases and six (10%) of 62 controls died during the study period.

Interpretation: In this cohort of patients with rheumatic and musculoskeletal diseases in a geographical region with a high prevalence of COVID-19, a poor outcome from COVID-19 seems to be associated with older age and the presence of comorbidities rather than the type of rheumatic disease or the degree of pharmacological immunosuppression.

Funding: None.
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http://dx.doi.org/10.1016/S2665-9913(20)30169-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302769PMC
September 2020

Effectiveness of reproductive health counseling of women with systemic lupus erythematosus: observational cross-sectional study at an academic lupus clinic.

Rheumatol Int 2021 Feb 7;41(2):403-408. Epub 2020 Aug 7.

Rheumatology Department, Centro Hospitalar Universitário de Coimbra, Praceta Professor Mota Pinto, 3000-075, Coimbra, Portugal.

Systemic lupus erythematosus (SLE) affects women of childbearing age. To optimize fetal and maternal outcomes, effective reproductive health counseling is crucial. To analyze the effectiveness of reproductive health counseling in women with SLE and identify gaps in patient educational needs. Cross-sectional study including women aged 18-45 years fulfilling ACR'97 and/or SLICC criteria, followed at an academic lupus clinic. Participants fulfilled a questionnaire evaluating brief obstetric history, knowledge about impact of SLE in pregnancy outcomes, recall of reproductive health counseling, contraception use and reproductive healthcare received. Effectiveness of reproductive health counseling was analyzed, and potential predictors of contraceptive use (age, previous spontaneous abortion, level of knowledge about SLE and reproductive planning) were tested by multiple regression analysis. We enrolled 108 women (mean age: 34.4 ± 7.1 years; mean disease duration: 10.3 ± 7.3 years). 64.8% of the patients recalled receiving information about family planning, and 81% about contraception. Only 38% declared to be well informed about the impact of SLE on pregnancy. In this cohort, 23.2% wanted a pregnancy in the future; the remainder already had the children they wanted or planned a subsequent pregnancy. Contraceptive use was reported by 79.6% of the patients (oral contraceptives by 39.8% and intrauterine device by 20.4%), while 11.1% reported unprotected intercourses. No statistically significant predictors of contraceptive use were identified. In this academic Lupus Clinic, most SLE women of childbearing age received effective reproductive health counseling and use contraceptive methods. Their unmet needs were identified to guide optimization of patient counseling.
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http://dx.doi.org/10.1007/s00296-020-04671-9DOI Listing
February 2021

"APS pregnancy - The offspring".

Lupus 2020 Oct 4;29(11):1336-1345. Epub 2020 Aug 4.

Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.

Background: Antiphospholipid antibody syndrome (APS) is an autoimmune disease that affects women in childbearing age. In recent years, great improvements were achieved in the management of pregnancies in these women. Prematurity could be an issue in these pregnancies, mainly due to the direct pathogenic effect of antiphospholipid antibodies (aPL) on the placental surface. Maternal IgG aPL can cross the placenta and theoretically interact with the growing fetus; it could reach the fetal brain because of the incompleteness of the fetal blood-brain barrier: whether this can have an effect on brain development is still debated. Neonatal thrombosis episodes have been described in children positive for aPL, not always associated with maternal antibody positivity, suggesting the hypothesis of a possible aPL de novo synthesis in fetus and neonates.

Methods: A keyword-based literature search was conducted. We also described a case of neonatal catastrophic antiphospholipid syndrome (CAPS).

Results: Offspring of patients with APS are generally healthy but the occurrence of neonatal thrombosis or minor neurological disorders were reported.

Conclusions: The limited number of the available data on this sensitive issue supports the need for further studies. Clinical follow-up of children of mothers with APS seems to be important to exclude, in the neonatal period, the occurrence of aPL associated pathological events such as thrombosis, and in the long-term, impairment in learning skills or behavioral problems.
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http://dx.doi.org/10.1177/0961203320947154DOI Listing
October 2020

Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome.

Ann Rheum Dis 2020 10 30;79(10):1286-1289. Epub 2020 Jul 30.

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Lombardia, Italy.

Objectives: The outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with 'standard-of-care' (SoC).

Methods: In the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5-19 March 2020, were treated with 'SoC' (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction).

Results: Patients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%) 63.6% (SE=4.1%), p=0.001). Cox proportional hazards regression survival analysis showed that a lower risk of death was independently associated with colchicine treatment (HR=0.151 (95% CI 0.062 to 0.368), p<0.0001), whereas older age, worse PaO2/FiO2, and higher serum levels of ferritin at entry were associated with a higher risk.

Conclusion: This proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.
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http://dx.doi.org/10.1136/annrheumdis-2020-217712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509521PMC
October 2020

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19).

Clin Exp Rheumatol 2020 Jul-Aug;38(4):748-753. Epub 2020 Jul 28.

Italian Society for Rheumatology, Milan, Italy.

Objectives: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance.

Methods: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry.

Results: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death.

Conclusions: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments.
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July 2020

Impact of the new 2019 EULAR/ACR classification criteria for Systemic Lupus Erythematosus in a multicenter cohort study of 133 women with undifferentiated connective tissue disease.

Arthritis Care Res (Hoboken) 2020 Jul 23. Epub 2020 Jul 23.

Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, S. Giovanni Bosco Hospital, Turin, Italy.

Objective: We aimed to investigate the impact of applying the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) in a previously described cohort of women with undifferentiated connective tissue disease (UCTD).

Methods: This study included 133 women with UCTD. At the time of inclusion into the study, none of the patients meet any classification criteria for other defined systemic connective tissue disease.

Results: When applying the 2019 EULAR/ACR classification criteria to the cohort, 22 patients (17%) fulfilled the classification criteria of SLE. Patients classified as SLE had significantly higher frequency of mucocutaneous manifestations (23%vs.5%;p=0.007), arthritis (59%vs.17%; p<0.001), isolated urine abnormalities (18%vs.1%;p<0.001) and highly specific antibodies (50%vs.15%;p<0.001). At follow-up, these patients were statistically significantly more likely to fit also the ACR 1997 and SLICC criteria (18.2%vs. 1.8%;p<0.001). Patients who were diagnosed as SLE per the ACR 1997 and SLICC criteria during the follow-up scored significantly more points in the new 2019 EULAR/ACR classification criteria when compared to the other UCTD patients (mean score 8.3±3.7 vs. 4.5±4;p<0.05).

Conclusion: When applying the 2019 EULAR/ACR criteria for SLE in a cohort of patient with UCTD, we observed that in up to 17% of cases the original classification could be challenged. New implementation will help to early identify patients at higher risk of developing more severe CTD manifestations.
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http://dx.doi.org/10.1002/acr.24391DOI Listing
July 2020

Long-term treatment with tocilizumab in giant cell arteritis: efficacy and safety in a monocentric cohort of patients.

Rheumatol Adv Pract 2020 15;4(2):rkaa017. Epub 2020 May 15.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili di Brescia.

Objective: The efficacy of tocilizumab (TCZ) in GCA is supported by two randomized controlled studies, in which TCZ allowed remission to be achieved after 52 weeks of treatment. However, after discontinuation of treatment, half of the patients relapsed. The aim of this study was to analyse the efficacy and safety of long-term treatment with TCZ and the role of fluorodeoxyglucose (FDG)-PET/CT scanning in the follow-up of these patients.

Methods: We collected the clinical data of a monocentric cohort of GCA patients retrospectively.

Results: Thirty-two patients were treated with TCZ [25 males and 7 females; age = 74 (59-81) years]. Most of them achieved and maintained clinical remission (1 month: 69%; 3 months: 91%; 6 months: 96%; 12 months: 100%), with serological and FDG-PET/CT scan improvement and a reduction of concomitant glucocorticoid therapy. Nineteen patients were treated for >52 weeks, and in 13 of them a dose tapering was performed, whereas in 2 cases TCZ was suspended for disease remission. Only two patients relapsed: one during TCZ tapering and one after TCZ discontinuation. Ten cases of mild infections and a case of urinary sepsis were reported; in patients treated for >1 year there was no increase in the incidence of side effects compared with patients treated for <12 months.

Conclusion: In our cohort of patients, we confirmed the efficacy of TCZ in the induction and maintenance of remission of GCA, demonstrating an important steroid-sparing effect and a good safety profile. Long-term treatment seems to prevent relapse of the disease, suggesting that TCZ treatment can be continued for >52 weeks with efficacy and safety.
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http://dx.doi.org/10.1093/rap/rkaa017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359771PMC
May 2020

Beyond current concepts in anti-phospholipid syndrome: The 16th International Congress on Anti-phospholipid Antibodies (ICAPA) in Manchester.

Autoimmun Rev 2020 Sep 11;19(9):102615. Epub 2020 Jul 11.

Experimental Laboratory of Immunological and Rheumatologic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Milan, Italy; Unit of Allergology, Immunology and Rheumatology, IRCCS Istituto Auxologico Italiano, Milan, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2020.102615DOI Listing
September 2020

Prevalence, specificity, and clinical association of anti-phospholipid antibodies in COVID-19 patients: are the antibodies really guilty?

medRxiv 2020 Jun 19. Epub 2020 Jun 19.

Background: Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPL) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-β GPI and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-β GPI antibodies was not reported.

Aim: To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-β GPI antibodies.

Methods: ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events.

Results: Anti-β GPI IgG/IgA/IgM were the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM were detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of β GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-β GPI nor with thrombosis.

Conclusion: aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against β GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.
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http://dx.doi.org/10.1101/2020.06.17.20134114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310661PMC
June 2020
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