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

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

Management of recurrent thrombosis in antiphospholipid syndrome

One of the challenges of managing patients with antiphospholipid syndrome is the prevention of rethrombosis (secondary prophylaxis). Risk stratification, i.e. traditional cardiovascular and thrombosis risk factors, systemic autoimmune diseases, antiphospholipid antibody profile, and the intensity of anticoagulation are all relevant to the management of APS patients with recurrent thrombosis. The paper will review "state of the art" strategies for optimizing therapy for APS patients with recurrent thrombosis

Pregnancy implications for systemic lupus erythematosus and the antiphospholipid syndrome

Multidisciplinary approach and patient counselling have been the key points in the improvement of the management of pregnancy in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Most of these women can have successful pregnancy when thoroughly informed and instructed on several different issues. Disease activity should be in stable remission prior to pregnancy in order to reduce the chance for flare during pregnancy. To this purpose, medications must be modulated: "safe" drugs should be continued throughout pregnancy, embryotoxic/foetotoxic drugs should be withdrawn timely, and beneficial drugs such as low dose aspirin and heparin should be added for prophylaxis of maternal and foetal outcome, especially in the presence of antiphospholipid antibodies. The safety profile of anti-rheumatic drugs during pregnancy and breastfeeding should be kept constantly updated, as new data from inadvertent exposure accumulates and new drugs (especially biological agents) are available. Patients may carry autoantibodies that can negatively affect the baby, being neonatal lupus the prototypical case of passively acquired autoimmunity. Research has been greatly active in this field and more information on risk stratification and management are now available for counselling. The effect of both autoantibodies and drug exposure has been evaluated in the offspring: some concerns about learning disabilities have been raised, but these are treatable conditions that are likely to be overcome. To counsel a woman with SLE/APS during childbearing age means also to deal with contraception. Despite the "preferred choice" - combined oral contraceptive - may not be suitable for most of the patients, other options are available and should be offered and discussed with the patient. Fertility is not generally affected in SLE/APS patients, but those cases who require assisted reproduction techniques should be carefully evaluated and managed

Long-term outcome of children born from mothers with autoimmune diseases

Autoimmune diseases often affect young women and this may represent a problem in family planning. Pregnancies in these patients may carry several complications but nowadays the continued amelioration in treatment and management has greatly improved the pregnancy outcome. The main concern of these women obviously is the short- and long-term outcome of their children. A child born from a woman with autoimmune disease is potentially exposed in utero to maternal autoantibodies, cytokines, and drugs, and each item could impair his or her development. In addition, the maternal genetic heritage can favor autoimmunity. All these items could have a role, for example, in the development of autoimmune diseases (the same as the mother or different ones) or neurological disorders. Data in literature are controversial. This review will gather the available data possibly providing a useful tool for counseling future mothers

CXCL-13 serum levels in patients with rheumatoid arthritis treated with abatacept

Objectives: C-X-C motif chemokine 13 (CXCL-13), which is expressed by synovial follicular dendritic cells and activated mature antigen-experienced T-helper cells, has been described as a surrogate marker of lymphoid phenotype of synovitis in rheumatoid arthritis (RA). A preferential response to anti-interleukin-6 receptor (IL-6R) as compared to anti-tumour necrosis factor alpha (TNFα) monotherapy has been described in patients with increased levels of CXCL-13. We hypothesised that serum levels of CXCL-13 could be used as a biomarker of response to treatment with abatacept (ABA), a T-cell co-stimulation blocker. Methods: Serum levels of CXCL-13 and of soluble intracellular adhesion molecule 1 (sICAM-1) (a putative marker of the myeloid subtype of synovitis) were measured by indirect solid-phase enzyme immunoassays, before (T0) and after 6 months of therapy with ABA (T6) in 63 patients with RA. Circulating T follicular helper cells and B cell subpopulations were identified by flow-cytometry. Results: At T0, CXCL-13 serum levels were higher in RA patients than in healthy controls (p=0.0001) and correlated with disease activity, while no difference between the two groups was observed as far as sICAM-1 levels. Serum levels of CXCL-13 levels decreased after therapy with ABA both in patients who achieved a clinical response (p<0.01) and in non-responders (p=0.01), whereas sICAM-1 levels did not significantly change. When comparing RA patients who responded to ABA with non-responders no significant difference of baseline serum levels of CXCL-13 was observed. Conclusions: CXCL-13 serum levels are raised in RA patients and decrease after therapy with ABA. We were not able to demonstrate that serum CXCL-13 levels predict the clinical response to ABA in RA patients

Long-term neurodevelopmental outcome of children born to prospectively followed pregnancies of women with systemic lupus erythematosus and/or antiphospholipid syndrome

Background Systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are autoimmune diseases that affect women of childbearing age. Maternal IgG antiphospholipid antibodies (aPL) can cross the placenta during pregnancy and theoretically reach the fetal brain. Some studies showed an increased number of learning disabilities in these children. Objectives To evaluate the long-term neurodevelopmental outcome of 40 children (median age 7.4 years) born to mothers with SLE and/or APS carrying positive IgG aPL during the third trimester of pregnancy. Methods Children were checked for neurological physical exam and intellectual/cognitive functioning by the Wechsler scale for corrected age. We submitted to the mothers the Child Behavior CheckList (CBCL) and a homemade set of questions created by pediatric neurologists. Results In all children neurological physical exam and intelligence levels were found to be normal. A cognitive impairment or a discrepant cognitive profile was found in 3 (7%) and 11 (28%) children, respectively. Learning disabilities were diagnosed in 3 children (19% of school-age children), all born to mothers with triple aPL positivity. A history of epilepsy was shown in four children (10%)

A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus

Nowadays, most of the young women affected by Systemic Lupus Erythematosus (SLE) can carry out one or more pregnancies thanks to the improvement in treatment and the consequent reduction in morbidity and mortality. Pregnancy outcome in these women has also greatly improved in the last decades. A correct timing for pregnancy (tailored on disease activity and established during a preconception counselling), together with a tight monitoring during the three trimesters and the post-partum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently milestones of the management of pregnancy in SLE patients. Nevertheless, the increasing knowledge on the compatibility of drugs with pregnancy has allowed a better treatment of these patients, by choosing medications that control maternal disease activity without harming the foetus. However, particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis and patients with aPL positivity or Antiphospholipid syndrome, who are at higher risk for maternal and foetal complications, but also patients with anti-Ro/SSA and/or anti-La/SSB antibodies, because of the risk of neonatal lupus. A discussion on family planning, as well as counselling on contraception, should be part of the everyday-practice for physicians caring for SLE women during their reproductive age. Another issue is the possible reduction of fertility in these women, that can be due to different reasons. Consequently, the request for assisted reproduction techniques has been increasing in the last years, so that rheumatologists and gynaecologists should be prepared to counsel SLE patients also in this particular setting

Managing puerperium in patients with systemic autoimmune diseases: an update

Introduction: Puerperium is a critical period for patients affected by autoimmune rheumatic diseases for the risk of disease's flares and difficulties in treating lactating mothers. We want to summarize the literature data about psychological and pharmacological management of these patients and possible risk factors of disease's flares. Areas covered: We made a narrative review on recent studies about puerperium in rheumatic autoimmune diseases patients. Expert opinion: The physicians involved in management of patients during puerperium and in the follow-up of babies need to agree on maternal treatment because they need to reassure mothers about the safety of the prescribed medications. Furthermore, women with rheumatic diseases could present some musculoskeletal limitations and psychological problems, such as postpartum depression, which can lead to a sense of inadequacy to the mother's task. Families and physicians should be aware of these possible complications and support the new mothers providing correct counseling and practical help

The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation

To analyze the glycosylation of anti-β2GP1, we investigated purified IgG from healthy children, patients with APS, and asymptomatic adult carriers of antiphospholipid antibodies. We observed that in the sera of healthy children and of patients with APS, IgG3 and IgG2 were predominant, respectively. The potentially protective anti-β2GP1-IgM was lower in the sera of healthy children. Although anti-β2GP1-associated C1q did not differ between children and patients with antiphospholipid syndrome, the associated C3c was significantly higher in the sera of healthy children. This indicates a more efficient clearance of anti-β2GP1 immune complexes in the healthy children. This clearance is not accompanied by inflammation or coagulatory events. It is likely that the most important pathogenic factor of the anti-β2GP1-IgG is related to the different glycosylation observed in healthy and diseased individuals. We detected a significantly higher sialylation of anti-β2GP1-IgG isolated from the sera of healthy children and asymptomatic adults when compared with that of patients with clinically apparent antiphospholipid syndrome. Low sialylated IgG reportedly ameliorates inflammation and inflammation promotes hyposialylation. Thus, both reactions create a vicious circle that precipitates the pathology of the antiphospholipid syndrome including thrombus-formation. We conclude that the increased sialylation of anti-β2GP1-IgG of sera of healthy individuals limits their pathogenicity