Libman-Sacks Endocarditis With Triple Valvular Involvement.

Annals for Educators - 19 November 2019.

Libman-Sacks endocarditis (LSE) is a form of nonbacterial thrombotic endocarditis (NBTE) observed in patients with malignancies, systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), resulting from endothelial injury in a hypercoagulable state. The mitral and aortic valves are most commonly affected. Complications can include valvular injury, heart failure (HF), and widespread embolic events. We present a rare case of embolic stroke caused by NBTE in a 51-year-old man with no significant medical history. The patient presented to the emergency department with the sudden onset of slurred speech, numbness, and weakness in his right hand. Physical examination revealed Janeway lesions, splinter hemorrhages, and widespread livedo reticularis. Laboratory tests showed elevated anticardiolipin antibody (aCL-IgM), increased BNP and high-sensitivity troponin, thrombocytopenia (68,000/μL), and elevated homocysteine. Repeated blood cultures were negative. Computed tomography (CT) of the brain revealed chronic right posterior temporal, occipital, and left occipital infarctions. Magnetic resonance imaging (MRI) of the brain demonstrated numerous small foci of early subacute ischemia in both cerebral hemispheres and the left cerebellar hemisphere. A transthoracic echocardiogram (TTE) identified a 0.93 x 0.51 cm mobile echodensity near the right coronary cusp. Transesophageal echocardiography (TEE) confirmed verrucous and nodular vegetations with heterogeneous echodensity at the commissural border of both aortic valve leaflets, severe aortic regurgitation (AR), and reduced left ventricular ejection fraction (LVEF = 45–50%). The patient was diagnosed with an embolic stroke caused by LSE in the context of underlying APS. He was treated with low molecular weight heparin (LMWH), vancomycin, and piperacillintazobactam (Zosyn). Subsequently, he underwent mechanical aortic valve replacement followed by warfarin therapy (target INR 3-4). Intraoperative findings confirmed thickening and numerous tiny nodular vegetations on the aortic valve. This case highlights the importance of early diagnosis of embolic stroke caused by NBTE in young patients without significant medical history. Prompt and appropriate treatment, including antibiotics, anticoagulants, and surgery, is crucial to prevent serious complications.

Background Cardiovascular involvement is frequent in systemic lupus erythematosus (SLE). Aortic insufficiency is a common valvular abnormality seen in patients with systemic lupus erythematosus (SLE), it may be caused by a primary valve pathology or by an aortitis One of the cardiac manifestations associated with SLE and antiphospholipid syndrome (APLS) is Libman–Sacks endocarditis, also known as non–bacterial thrombotic endocarditis Although rare, there are reported cases of lupus aortitis which has also been associated with dissection, aneurysm and thrombus. Case Report We present a case of a 40 –years–old lady with lupus glomerulonephritis requiring immunosuppression and dialysis, who presented to the emergency department with fever and dyspnea. She was first treated with dialysis. Blood cultures drawn from central venous catheter peripheral were positive for staphylococcus epidermidis, the cultures from peripheral blood was negative instead.Transthoracic and transesophageal Echocardiography showed severe aortic regurgitation (not present three month earlier) with doubt valvular vegetations and with a focal enlargement of the aortic root (figure 1, 2).The patient met one major criterion (blood culture) and two minor criteria (high risk and fever), implying possible infective endocarditis. The patient was then started on intravenous antibiotics (vancomycin) and immunosuppression was reduced. Given the hemodynamic instability due to the severe aortic insufficiency, an Heart CT scan was performed to planned the surgical intervention. The CT scan confirmed the presence of small, multiple vegetation attached to the aortic leaflet and an aortic dissection on the right coronary cusp (figure 3). She proceeded to urgent surgery with aortic valve and aortic root replacement, the histology revealed evidence of Libman–Sacks endocarditis and aortitis. Discussion Our patient showed two different cardiovascular complications of SLE: the more frequent Libman –Sack endocarditis and the rare lupus aortitis associated to aortic dissection.The patient had risk factors for infective endocarditis and she did fulfil the modified Duke’s criteria for infective endocarditis and was treated with antibiotics and with a reduction of immunosuppression therapy. In fact, it can be difficult to distinguish between infective endocarditis and Libman–Sacks endocarditis especially in the setting of risk factors for both. Antibiotics and immunosuppressants should be used both.

Relationships between viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) are still elusive. Recent reports demonstrated the association of some viral infections with peculiar clinical events in the general population, such as cytomegalovirus (CMV) with arterial damage and Parvovirus B19 (PV-B19) with hematologic abnormalities. We planned to look for this kind of viral imprinting in SLE, hypothesizing that traces of specific features of some viral infections might be found in some subsets of seropositive SLE patients. In 60 SLE patients recruited at our nephrologic center, serology for CMV, PV-B19, Epstein-Barr virus viral capsid antigen (EBV-VCA), Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr virus early antigen (EBV-EA) was performed. χ² and ANOVA were employed to compare the frequency and titers of antiviral antibodies in SLE patients with groups of transplant, hemodialysis and blood donor subjects. χ², Fisher’s test, Bonferroni and Scheffe’s test were employed to compare the different biochemical/clinical features between seropositive and seronegative SLE patients. Univariate and multivariate analysis (logistic regression models) were employed to evaluate the odds ratio (OR) of different risk factors for vascular events (including Raynaud’s phenomenon, deep venous thrombosis) and hematologic abnormalities (including severe anemia, leukopenia and thrombocytopenia). Anti-CMV (82%), anti-PV-B19 (60%), anti-EBV-VCA (92%) and EBV-EA (45%) IgG antibodies were frequent in SLE, with higher prevalence in comparison with the blood donor group and higher titers in comparison with transplant and hemodialysis groups. CMV seropositivity was a highly significant risk factor for Raynaud’s phenomenon (OR +α in univariate and multivariate analysis = 13.51 using a correction of 0.5 in case of a zero event), but not for venous vascular events (OR = 1.31). An increased though not significant risk factor was found for antiphospholipid antibodies (OR = 2.71, p = 0.19), while the presence of nephrotic syndrome during the follow-up was a significant protective factor (OR = 0.15, p = 0.035). There was no significantly increased OR for PV-B19 seropositivity in cases with severe anemia (OR = 2.09, p = 0.29). No significant associations were found with the status of EBV reactivation. In conclusion, our results support the hypothesis that viral infection may imprint the course of SLE leading to specific clinical subsets (i.e. CMV and ‘vascular’ SLE, with more frequent Raynaud’s phenomenon and a less frequent typical histological renal picture responsible for nephrotic syndrome). Further prospective studies are justified to validate these correlations, mainly dealing with associations between acute viral infections and vascular events, thus eventually leading to a better understanding of mutual relationships between viruses and SLE.

Libman-Sacks endocarditis (LSE), or nonbacterial thrombotic endocarditis (NBTE), is a rare condition most commonly associated with systemic lupus erythematosus (SLE), but it may also occur in patients with malignancies. NBTE is an underrecognized cause of cancer-associated embolic strokes of undetermined source. We report the case of a 68-year-old female with metastatic pancreatic adenocarcinoma who presented with acute visual disturbances and headaches. Neuroimaging revealed multiple embolic infarcts in different vascular territories. Transesophageal echocardiography (TEE) identified a mass on the posterior mitral valve, consistent with sterile thrombus formation. Laboratory and imaging studies confirmed advanced pancreatic cancer, creating a hypercoagulable state likely responsible for NBTE. The patient was managed with anticoagulation using low-molecular-weight heparin and palliative chemotherapy targeting the underlying malignancy. Despite these interventions, her clinical course progressed with recurrent embolic events and systemic decline, ultimately necessitating hospice care.This case highlights the diagnostic challenges of NBTE in malignancy, emphasizing the need to consider this condition in patients with multiple embolic strokes of varying ages. Early recognition through neuroimaging and echocardiography is essential for timely anticoagulation and multidisciplinary management. Clinicians should maintain a high index of suspicion for NBTE in patients with prothrombotic cancers, such as pancreatic adenocarcinoma, as prompt diagnosis can guide appropriate therapy and optimize quality of life.

ObjectiveAssess healthcare costs associated with systemic lupus erythematosus (SLE) flares among patients with and without lupus nephritis (LN).MethodsThis retrospective cohort study used medical and pharmacy claims data from the United States-based Optum Clinformatics database to identify adults with SLE between 1 January 2016, and 31 December 2018. Index was the date of a patient’s earliest SLE diagnosis claim during the identification period. Patients were categorized based on ICD-9/-10 diagnosis codes into one of two cohorts: SLE with LN (LN) and SLE without LN (non-LN). Baseline characteristics were assessed in the 12 months preceding index (baseline period). The presence, severity, and healthcare costs (in 2019 US dollars) of flares were determined in the 12 months following index (follow-up period).ResultsOverall, 11,663 patients with SLE were included (LN, n = 2916; non-LN, n = 8747). During the baseline period, a greater proportion of patients in the LN cohort versus non-LN cohort had a Charlson Comorbidity Index score ≥4 (72.5% vs 13.7%) and inpatient stays (41.0% vs 17.0%). A total of 12,190 flares were identified during the follow-up period (LN, 3494; non-LN, 8696). A greater proportion of flares experienced by patients with LN versus those without LN were moderate (61.2% vs 53.6%) and severe (10.6% vs 5.4%). The mean (standard deviation [SD]) number of moderate and severe flares per patient was greater among the LN cohort than the non-LN cohort (moderate: LN, 1.8 [1.2] and non-LN, 1.4 [1.2]; severe: LN, 0.2 [0.6] and non-LN, 0.1 [0.3]). The mean (SD) total healthcare costs associated with SLE flares of any severity were greater for patients with LN (LN, $5842 [9604]; non-LN, $2600 [4249]). The mean (SD) cost per flare increased with severity (mild: LN, $2753 [4640] and non-LN, $1606 [2710]; moderate: LN, $4561 [7156] and non-LN, $2587 [3720]; severe: LN, $29,148 [27,273] and non-LN, $14,829 [19,533]).ConclusionsPatients with SLE with LN have greater healthcare costs than those without LN. Flares among patients with LN were more frequent, severe, and costly than among patients without LN. This highlights the need for treatments that prevent or reduce flares among patients with SLE, both with and without LN.

The possible effect of expressive plasma level of miRNA-21-5P on the serum level of IL-23 in with and without lupus nephritis patients

In this review, the cardiac lesions which develop in association with the various collagen-vascular diseases are described. In rheumatoid arthritis, the most frequent lesions are: fibrous obliterative pericarditis, with pericardial deposits of calcium, fibrin, cholesterol, and rheumatoid granulomas; granulomatous or nonspecific myocarditis; valvulitis, vasculitis, and amyloid deposits. In ankylosing spondylitis, the lesions involve mainly the valves (aortic and mitral valves) and the aorta. In systemic lupus erythematosus, the predominant cardiovascular lesions are: pericarditis, Libman-Sacks endocarditis, nonspecific myocarditis, vasculitis with fibrinoid necrosis, and acceleration of atherosclerosis. In scleroderma, the main cardiac lesion is fibrosis with only scanty inflammatory cells; pericarditis and nonbacterial thrombotic endocarditis also occur. In dermatomyositis/polymyositis, fibrous or fibrinous pericarditis can occur, as well as myocarditis with infiltrates of lymphocytes and plasma cells and with degeneration and necrosis of myocytes; valvulitis is uncommon except when the disease is related to mucinous adenocarcinoma. In polyarteritis nodosa, various stages of necrotizing vasculitis involve all layers of the arterial walls; foci of myocardial necrosis of various sizes can occur in association with these lesions; cardiac hypertrophy related to hypertension and pericarditis related to uremia, may also be found. In Wegener's granulomatosis, pericarditis, inflammatory infiltrates, necrotizing granulomas, and vasculitis have been observed in the heart.

Pancréatite aiguë et syndrome hémophagocytaire au cours d’une poussée lupique: À propos d’une observation

BackgroundAntiphospholipid syndrome is an antibody mediated pro-thrombotic state leading to various arterial and venous thromboses. The syndrome can be either primary or secondary to other autoimmune diseases, commonly systemic lupus erythematosus. Cardiac involvement, in particular valvular disease is common in patients with antiphospholipid syndrome, occurring in about a third of these patients. Valvular diseases associated with antiphospholipid syndrome often occur as valve thickening and non-bacterial vegetation or Libman-Sacks endocarditis. Deposits of antiphospholipid immunoglobulin and complement components are commonly observed in the affected valves, suggesting an inflammatory process resulting in valvular vegetation and thickening. Libman-Sacks endocarditis has a high propensity towards mitral valve, although haemodynamically significant valvular dysfunction is rare.Case presentationWe present a successful aortic valve replacement with cardiopulmonary bypass in a 48 years old lady with antiphospholipid syndrome, who has severe aortic regurgitation as a result of Libman-sacks endocarditis. Antiphospholipid antibodies were positive and the clinical data showed both negative cultures and infective parameters. Surgically resected vegetations revealed sterile fibrinous and verrucous vegetations on aortic valve. Valve replacement and the course of cardiopulmonary bypass was uneventful, and the patient was discharged well.ConclusionsClassically Libman-Sacks endocarditis is often and more commonly associated with autoimmune diseases such as systemic lupus erythematosus, although it can occur in both primary and secondary antiphospholipid syndrome. It is not a common entity, and it is a frequent underestimated disease as most clinicians do not routinely screen for valvular lesion in patients with antiphospholipid syndrome unless they are symptomatic. However, due to its high prevalence of cardiac involvement, clinicians should have a high index of suspicion in the attempt to minimize cardiovascular and haemodynamic complications. Valve surgery in patients with antiphospholipid syndrome carries considerable early and late morbidity and mortality, usually caused by thromboembolic and bleeding events. The perioperative anticoagulation management and haemostatic aspect of antiphospholipid syndrome present an exceptional challenges to clinicians, surgeons, anaesthetists and laboratory personnel.

Background and Aims The regional epidemiology of Systemic lupus erythematosus (SLE) and lupus nephritis (LN) within the same country is poorly understood. Being a rare disease, its severity may be influenced by local expertise and treatment protocols, especially when healthcare systems are fragmented, like in Spain (17 different healthcare systems in 17 Autonomous Community (AACC), population range 319.796 to 8.472.407), resulting in potentially different levels of expertise in regional referral centers. Additional heterogeneity may derive from different specialists (rheumatology, internal medicine, nephrology) caring for SLE and LN. We aim to investigate the disease burden of SLE and LN in Spain and its AACC between 2019 and 2021, and to characterize factors that may influence this burden. Method The primary diagnostic data and average cost of SLE and NL hospitalization were extracted from the Minimum Basic Data Set (MBDS, Ministry of Health) that contains data from private and public hospitals. Sociodemographic data were obtained from the National Statistics Institute. Results From 2019 to 2021, there were 872 LN and 3612 SLE nationwide hospitalizations. Over 60% occurred in Andalucia, Catalonia, and Madrid, which account for 48% of Spanish population. Nationwide, the incidence of LN and SLE hospitalization was 1.44 and 4.59 per 100 000, respectively. However, regional variability was large, with a 3.7-fold difference for LN and a 7.3-fold difference for SLE between Madrid and Valencia, 2 of the more populated AACC. The median LN/SLE hospitalization ratio was 0.33. Relative risk for hospitalization, compared to the national mean, ranged in AACC from 0.37 (Baleares) to 2.55 (La Rioja) for LN and from 0.22 (Baleares) to 3.67 (Ceuta and Melilla) for SLE (Fig. 1A). Heterogeneity was larger at the provincial level where 10/50 provinces had significantly higher or lower relative risk than the national mean (Fig. 1B). The length of SLE/LN hospitalizations was very variable across specialties and AACC. There was a trend for shorter duration in Nephrology and longer in Internal Medicine for both LN and SLE. Nephrology was mainly responsible (76%) for LN hospitalization, with regional differences. For SLE hospitalization, Nephrology was also most commonly in charge. Heterogeneity was larger at the province level within the same AACC. The average All-Patient-Related (APR) cost per LN and SLE hospitalization episodes was €5254 and €4376, respectively, with significant geographical variability. Total annual hospitalization costs varied significantly among AACC, ranging from €8683 (Ceuta and Melilla) to €682512 (Catalonia) for LN and from €68361 (Ceuta and Melilla) to €2229456 (Madrid) for SLE. Adjusted per million population, total LN hospitalization cost ranged from €27920 (Baleares) to €179248 (La Rioja), and SLE cost from €91563 (Baleares) to €399693 (Ceuta and Melilla). When adjusted by €1000 of average household net income, the budget burden of LN hospitalization was highest in La Rioja (€5812 per €1000 of average household net income) and lowest in Baleares (€809 per €1000), while for SLE was highest in Murcia (€11186 per €1000) and lowest in Baleares (€2652 per €1000) (Fig. 2A,B). Conclusion In conclusion, the burden of LN and SLE hospitalization is heterogeneous across and within Spanish AACC, with large regional differences in the distribution of cases, costs and specialists who care for these patients. The analysis of these differences may contribute to benchmarking of best practices, decreasing clinical practice heterogeneity, optimizing care for SLE and LN and improving outcomes.

Soluble form of vascular cell adhesion molecule-1 in systemic lupus erythematosus and discoid lupus erythematosus

The available clinical as well as experimental studies implicate participation of T regulatory (Treg) subsets in the pathogenesis and course of systemic lupus erythematosus (SLE). Introduction of the CD4+CD25+CD127− and CD4+CD25+Foxp3+ regulatory subpopulations analysis into immunological processes assessment and disease activation prognosis in patients with lupus nephritis (LN) may improve monitoring of disease activity and enable an early, and thus more effective, therapeutic treatment. The main goal of the study was to investigate whether the quantitative changes of Treg subpopulations are related to the clinical status of patients with LN. Fifty-four adult SLE patients divided into two groups according to their SLEDAI and renal SLEDAI scores were enrolled into the study. Subpopulations of CD4+CD25+CD127− and CD4+CD25+Foxp3+ phenotypes were determined by flow cytometry. The control group had higher absolute number of CD4+CD25+Foxp3+ cells compared with the study group (p < 0.001). Also, significant inverse correlation in the absolute number of CD4+CD25+Foxp3+ cells and SLEDAI score was observed. There were significant differences in the percentage and absolute number of CD4+CD25+Foxp3+ lymphocytes between active and non-active LN groups. The study group had statistically lower values of CD4+CD25+CD127− cells, both in the percentage (p < 0.001) as well as their absolute number (p = 0.014) compared to the control group. There were also statistically significant positive correlations between the absolute number of CD4+CD25+CD127− and CD4+CD25+Foxp3+ Tregs. In conclusion: (1) reduction in the number of regulatory CD4+CD25+Foxp3+ cells is a promising indicator of the activity of SLE, particularly of renal involvement; (2) determination of the number of regulatory cells using the CD4+CD25+CD127− phenotype is unreliable in patients with SLE.

O054 / #505Topic:AS24 - SLE-TreatmentABSTRACT CONCURRENT SESSION 09: SLE THERAPY – REVISITING OLD DRUGS AND UNLOCKING HIDDEN POTENTIAL OF NEW MEDICATIONS24-05-2025 10:40 AM - 11:40 AMBackground/PurposeAddition of biologic drugs to standard of care (SoC) in systemic lupus erythematosus (SLE) is advised in refractory patients. Evidence is needed on the effectiveness of early biologic use in influencing SLE course. In this cohort study, we aim to assess the effect of belimumab administration on disease progression in early active lupus patients.MethodsWe performed a multicentric observational study on patients with early SLE receiving either belimumab or SoC alone and compared the rate of EULAR/ACR 2019 criteria accrual between the 2 groups as a measure of lupus progression over time. Patients were defined as early active if they were diagnosed within 12 months from treatment initiation and displayed up to 2 EULAR/ACR clinical criteria, excluding major organ involvement, with active serology (ie, positive anti-dsDNA antibodies and/or decreased serum complement). Clinical, demographic and serological data were collected in an anonymized fashion at baseline and at 3, 6, and 12 months. Kaplan-Meier curves with log-rank comparison were used to assess criteria accrual throughout the first 12 month of follow-up.ResultsWe included 57 early active SLE patients, 24 (42.1%) receiving SoC alone and 33 (57.9%) receiving add on belimumab to SoC and followed up for at least 12 months from baseline. The groups were comparable in terms of age, gender, disease duration, background immunosuppression and overall disease activity at baseline. Patients doomed to early belimumab displayed higher mean SLICC and prednisone daily dosage (Table 1). Overall, 8.7 events/100-patients years occurred in our cohort. Twenty-five percent of patients on SoC vs 3.2% of patients on early belimumab accrued at least one EULAR/ACR criterion throughout the follow-up (p=0.035). Patients on SoC displayed development of skin rash (2 cases), arthritis (1 case), lupus nephritis (1 case), while one case of pericarditis occurred in the belimumab group. Criteria-free survival was significantly longer in patients receiving belimumab early as compared to those receiving SoC alone (log-rank 5.78, p=0.016) (Figure 1). Mean time-to-event (months) was shorter in patients on SoC alone (10.3± 3.33 vs. 11.8±1.07, p=0.027).Table 1.Baseline clinical and demographic features of early SLE patientsFigure 1.Kaplan-Meier curves depicting criteria-free survival in patient groupsContinuous variables expressed as mean±SD. HCQ, hydroxycholoroquine; IS, immunosuppressants; cSLEDAI-2K, clinical SLE-activity index 2000; SLICC-DI, SLICC damage indexConclusionsTimely use of belimumab in patients with early active SLE can significantly delay disease progression, potentially preventing development of severe manifestations.

Systemic lupus erythematosus (SLE) is a chronic disease that is characterized by an undulating course of exacerbations and remissions, and a major determinant of long-term prognosis is organ damage consequent to tissue injury that accompanies disease activity and toxicity of therapy. In this study, we evaluated which patients with SLE will develop an exacerbation and whether factors can be identified to predict the development of an exacerbation. Fifty-seven SLE patients (52 females) were included in this study. The exacerbation of SLE was found in 15 patients (26.3%). A relatively increased incidence of an exacerbation was found in younger SLE patients. An increased percentage of patients who had lupus nephritis at the time of diagnosis of SLE was found in patients with a subsequent exacerbation when compared with that in those without it. Increased incidence of an exacerbation was observed in patients who had decreased number of WBC and platelets, decreased level of C3 and CH50, and the presence positivity of anti-Sm antibodies at the time of the diagnosis. This study suggests that age, renal involvement, and the presence of decreased number of WBC and platelets, decreased level of complements anti-Sm antibodies are predictors of exacerbation.