Systemic Lupus Erythematosus Flare Research Articles

Lymphadenopathy in systemic lupus erythematosus: no microbial trigger found by shotgun metagenomics in a retrospective study on 38 patients.

Lymphadenopathy is a classical manifestation of systemic lupus erythematosus (SLE) flare, occurring in approximately half of patients during the course of the disease. Lymphadenopathy in SLE is frequently associated with fever. Microbial infection may play a role in SLE onset and flares. Objectives of this study were to describe lymphadenopathy in the course of SLE and identify potential infectious triggers using microbial metagenomic analysis. We performed a retrospective monocentric study of 38 patients with SLE who had lymph node biopsy at baseline or during follow-up. Shotgun metagenomics were performed in patient's lymph node biopsy to look for microbial RNA and/or DNA. Lymph node pathological analyses revealed follicular and/or paracortical hyperplasia 73.7% of patients and histiocytic necrotizing lymphadenitis 23.7%. At the time of biopsy, SLE patients exhibited fever in 29%, splenomegaly in 10%, cutaneous manifestations in 47%, polyarthritis in 32%, seritis in 13% and lupus nephritis in 18%. Half of patients (50%) had increased CRP level, 35% had low C3, 65% had hypergammaglobulinemia. Microbial metagenomic analysis of lymph node biopsy did not reveal the presence of microbial DNA in 92% of patients, the presence of CMV in very small quantities in 2 patients, and the presence of HHV-7 in low quantities in a single patient. Despite suggestion that certain microorganisms may play a role in the pathogenesis and flares of SLE, our microbial metagenomic analysis study did not highlight possible infectious triggering factors. Further and better-designed studies are needed to confirm these results.

Lupus activity and pregnancy outcomes in systemic lupus erythematosus patients undergoing assisted reproductive therapy: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. While pregnancy and hormonal stress can trigger SLE flare-ups, the effects of assisted reproductive therapies (ARTs) on SLE patients are not well defined. We conducted a search of PubMed/Medline, Embase, and CENTRAL until March 20, 2024, to find observational studies assessing the prevalence of SLE flares and pregnancy outcomes following ARTs. Our analysis included random-effects meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for evaluating evidence quality. Five studies involving 237 SLE women who underwent ARTs were eligible. The meta-analysis indicated a prevalence of SLE flares at 17% (95% CI: 10-25%) with moderate-quality evidence. The pooled prevalence of arthritis flares was 7% (95% CI: 0-25%) with low-quality evidence. Successful pregnancy rates were 58% (95% CI: 43-72%), and live birth rates were 96% (95% CI: 83-100%), both with low-quality evidence. Moderate-quality evidence showed pregnancy complications, including preterm premature rupture of membranes (PPROM) at 8% (95% CI: 3-16%), miscarriages at 2% (95% CI: 0-9%), intrauterine fetal demise (IUFD) at 4% (95% CI: 0-11%), and preeclampsia at 7% (95% CI: 1-17%). Low-quality evidence showed preterm labor at 10% (95% CI: 0-32%) and ovarian hyperstimulation syndrome (OHSS) at 2% (95% CI: 0-11%). SLE flares, as well as pregnancy complications such as IUFD, miscarriage, PPROM, and preeclampsia in ART recipients, are equivalent to those in spontaneous conception. This indicates that ART is relatively safe for SLE patients with meticulous pregnancy planning. Key Points •Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. • Pregnancy in women with SLE poses elevated maternal and fetal risks compared to healthy women. • SLE flares and pregnancy complications while receiving ART are equivalent to those in spontaneous conception and ART is relatively safe for SLE patients.

Do novel inflammation biomarkers arising from routine complete blood count play a role in patients with systemic lupus erythematosus?

Laboratory-based biomarkers accurately presenting systemic lupus erythematosus (SLE) disease activity may have a practical value in clinical routine. As shown in many other conditions, complete blood count (CBC)-derived biomarkers may also play a role in SLE. We aimed to study for the first time the pan-immune-inflammation value (PIV, monocytes x platelets x neutrophils/lymphocytes) and the more established systemic immune-inflammation index (SII, neutrophils x platelets /lymphocytes) in SLE patients and correlate it with serological and clinical findings including disease outcomes. In this retrospective multicentric investigation, we reviewed the clinical records of 148 SLE who had an available CBC at baseline. The latter served for the determination of the neutrophil-to-lymphocyte ratio (NLR), SII, and the PIV. Control groups were studied as well. Univariable as well as multivariable statistics were employed. The values for baseline systemic immune-inflammation biomarkers (SIIB) studied were significantly (p < 0.0001) higher than those observed in healthy controls but comparable to those obtained from patients with other inflammatory conditions. Multivariable analysis revealed that ANA titer > 1:640 remained the only significant (p < 0.0001) baseline predictor of SLE flare (odds ratio: 7.6, 95% CI 3.1 to 18.8). Improvement of SLE following treatment was associated with the absence of lymphopenia as well as ANA > 1:640 (p = 0.041). The SLEDAI-2K significantly correlated with NLR, SII, CRP, lymphocytes, and monocytes only on univariable testing. Compared to healthy controls the CBC-based SIIB investigated are significantly increased in SLE patients. However, SIIB do not appear to be useful in managing SLE clinically. Nevertheless, we confirm that higher ANA titers can predict flares of SLE.

Managing macrophage activation syndrome SLE: Clinical and therapeutic insights

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with frequent hematologic complications, including leukopenia, thrombocytopenia, autoimmune hemolytic anemia, and, in rare cases, macrophage activation syndrome (MAS). MAS, a severe hyperinflammatory condition, presents diagnostic challenges due to its overlap with SLE flares, infections, and drug-related adverse effects. This case report presents a 22-year-old female with SLE who experienced clinical deterioration following methotrexate initiation, manifesting as fever, pancytopenia, and transaminitis. Differential diagnoses were considered, including MAS, infection, and methotrexate toxicity. Prompt recognition and management with corticosteroids and immunoglobulins led to clinical improvement, underscoring the complexity of diagnosing and treating MAS in SLE patients.

5175 A Rare Case of Type B Insulin Resistance Syndrome

Abstract Disclosure: S. Fatima: None. A. Champion: None. S. Ward: None. Q. Aziz: None. K.E. Izuora: None. Introduction: Severe insulin resistance may be defined as a severely diminished response to insulin’s biological effects and is characterized by substantial hyperinsulinemia and impaired glucose response to endogenous and exogenous insulin. We hereby present a rare case of Type B Insulin Resistance Syndrome (TBIRS). Case:40-years old female with history of systemic lupus erythematosus (SLE), diabetes mellitus was admitted with multiple rheumatologic complaints, including arthralgias, oral ulcers, skin rash, and hair loss secondary to SLE flare. Endocrinology was consulted for diabetes management. Her HbA1c had increased from 7.3% to 11.6% in 3 months despite taking Glargine 45 units daily, Lispro 15 units pre-meals and metformin. She noticed 80 lbs weight loss for past 6 months. Her BMI was 26 and exam showed acanthosis of neck, armpits, groin, hair loss on scalp, multiple genital ulcers, and facial rash. She was noted to have refractory hyperglycemia despite high insulin doses. By 14th day of hospitalization, she was on 287 units of insulin (3.4units/kg) daily. We suspected TBIRS in the setting of SLE. Metformin and pioglitazone were started. Further testing showed insulin level 152mIU/ml (2.6-14.9mIU/ml), C-peptide 1.7 ng/ml (1.1-4.4 ng/ml), islet-cell antibody negative, GAD-65 antibody &amp;lt;5 u/ml, insulin antibody 6.5 uU/ml, IGF-1 14 (79-259 ng/ml), adiponectin 13.3 (2.4-17.9 ug/ml), testosterone 7 (8-60 ng/dl), free testosterone &amp;lt;0.2 (0-4.2 pg/ml), total cholesterol 200 mg/dl (&amp;lt;200 mg/dl), triglycerides 85 mg/dl (&amp;lt;150 mg/dl), LDL 154 mg/dl (&amp;lt;100 mg/dl), HDL 29 mg/dl (&amp;gt;60 mg/dl). She was transferred to National Institute of Health for further care. She was confirmed to have TBIRS by insulin receptor antibody testing, started on regular insulin U500 initially, and then switched to IV insulin drip requiring up to 1700 units of insulin per hour. She received methylprednisolone, cyclophosphamide (2 doses), rituximab (2 doses), hydroxychloroquine and IV immunoglobulin. Her stay was complicated by hemophagocytic lymphohistiocytosis. She was discharged on U-500 Regular insulin, 1000 units with breakfast and 500 units with lunch, Prednisone 60 mg daily and Hydroxychloroquine. Two months later she was found unresponsive at home secondary to hypoglycemic seizures. She required dextrose drip and was discharged on Glargine 16 units and Lispro 6 units with meals. Conclusion: TBIRS is caused by a highly specific polyclonal autoantibody against the cell surface insulin receptor that decreases the cellular insulin response and causes refractory hyperglycemia. About 100 cases have been reported in literature. 60% of the cases are associated with SLE. The goal of therapy is to reverse the hypercatabolic state with high doses of insulin and to eliminate the autoantibodies with immunosuppressive therapy. The most common cause of mortality is hypoglycemia. Presentation: 6/3/2024

Macrophage Activation Syndrome in an Adolescent Male with Dialysis-Dependent Kidney Failure and Systemic Lupus Erythematosus Flares

Macrophage Activation Syndrome in an Adolescent Male with Dialysis-Dependent Kidney Failure and Systemic Lupus Erythematosus Flares

MATERNAL AND FETAL OUTCOME OF PREGNANCY IN SLE: A SINGLE CENTER SURVEY FROM PAKISTAN

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with multifactorial origins, affecting multiple organ systems. Pregnancy in women with SLE is associated with a higher risk of complications and adverse outcomes. This study aimed to evaluate maternal and fetal outcomes in pregnant patients with SLE. Objective: To analyse the maternal and fetal pregnancy outcomes in patients with SLE. Methods: This cross-sectional study was conducted over six months, from Jan 2024 to July 2024, after approval from the institutional ethical review board. Sixty-six pregnant women with SLE were enrolled based on specific inclusion and exclusion criteria. Detailed medical histories were collected, and patients were followed throughout pregnancy for maternal and fetal outcomes. Data was analyzed using SPSS version 26.0. Results: The mean age of the participants was 35.11 ± 7.27 years. Maternal complications included SLE flare in 47 (71.2%) patients, onset of disease during pregnancy in 4 (6.1%) patients, and normal pregnancy in only 15 (22.7%) cases. Fetal outcomes revealed intrauterine growth retardation (IUGR) in 12 (18.2%) cases and intrauterine death in 5 (7.6%) cases. Conclusion: Pregnancy in women with SLE is associated with significant maternal and fetal complications. The high prevalence of adverse outcomes underscores the need for careful monitoring and specialised care during pregnancy to improve prognoses.

Mycophenolate Mofetil and New-Onset Systemic Lupus Erythematosus

Anti-double-stranded DNA (dsDNA) antibody has been reported to have a close relationship with systemic lupus erythematosus (SLE) flares and participates in the pathogenesis of lupus nephritis (LN) as well as causing damage to other organs. However, whether early use of mycophenolate mofetil (MMF) could prevent SLE flares is not clear. To assess the efficacy and safety of MMF plus prednisone and hydroxychloroquine sulfate compared with prednisone and hydroxychloroquine sulfate alone in patients with SLE. This investigator-initiated, multicenter, observer-blinded randomized clinical trial enrolled 130 participants aged 18 to 65 years and was conducted in 3 hospitals across China. Treatment-naive patients with newly diagnosed SLE, a high titer of anti-dsDNA antibody, and no major organ involvement were included. The study was started September 1, 2018, and the follow-up was completed September 30, 2021. Data were analyzed from December 1, 2021, to March 31, 2022. Patients were randomized 1:1 to receive oral prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) (control group) or prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) plus MMF (500 mg twice daily) (MMF group) for 96 weeks. The primary outcome was the proportion of patients presenting with flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare Index. The secondary outcomes included the proportion with lupus low disease activity state at week 96, 36-Item Short Form Health Survey scores before and after treatment, proportion of adverse events (AEs), and changes in SLEDAI-2000 scores and prednisone doses. Among 130 randomized patients (mean [SD] age, 34.5 [12.5] years; 112 [86.2%] women), 119 (91.5%) completed the follow-up. The risk of severe flare was significantly lower in the MMF group (7 of 65 [10.8%]) vs the control group (18 of 65 [27.7%]) (relative risk [RR], 0.39 [95% CI, 0.17-0.87]; P = .01). Additionally, 1 of 65 patients in the MMF group (1.5%) and 9 of 65 in the control group (13.8%) manifested LN (RR, 0.11 [95% CI, 0.01-0.85]; P = .008). Most common serious study drug-related AEs were infections (20 of 65 [30.8%] in the control group and 22 of 65 [33.8%] in the MMF group). The findings of this randomized clinical trial suggest that MMF may reduce the rate of severe flare and lower the incidence of LN in patients with new-onset SLE and a high titer of anti-dsDNA antibody without major organ involvement. Chinese Clinical Trial Registry: ChiCTR1800017540.

Lupus flare and recurrent lupus nephritis following kidney transplantation in patients with lupus nephritis

AbstractBackgroundClinical manifestations and risk factors associated with systemic lupus erythematosus (SLE) flares, including recurrent lupus nephritis (LN), in patients with LN who undergo kidney transplantation have been unclear.MethodsKidney transplant recipients with LN from January 1995 to December 2021 were included in this study. A disease flare was defined as either an increase in the non‐renal SLE disease activity index score or the presence of biopsy‐proven recurrent LN.ResultsAmong a total of 93 patients with LN who underwent kidney transplantation, 11 patients (11.8%) experienced SLE flares during a median follow‐up period of 76.9 months (IQR, 43.0–122.4). The most common clinical manifestations of SLE flares were recurrent LN (4/11, 36.4%) and hematologic manifestations (4/11, 36.4%). Patients who had flares had significantly higher anti‐double‐stranded DNA (anti‐dsDNA) antibody titers both before and after transplantation. Furthermore, an increased anti‐dsDNA antibody level before transplantation was associated with a high risk of an SLE flare (HR, 1.030; p = .008). Conversely, preemptive transplantation was associated with a lower risk of a flare (HR, 0.617; p = .026). The rate of patient death‐censored graft survival was found to be considerably lower in patients with recurrent LN than in those without LN.ConclusionsApproximately 10% of patients with LN experienced an SLE flare after transplantation, with recurrent LN being the most frequent manifestation. Anti‐dsDNA antibody titers before transplantation were significantly related to the risk of an SLE flare. Notably, preemptive transplantation was associated with a reduced risk of flares following transplantation.

Clinical characteristics and risk factors for lupus flares in sub-Saharan Africa-retrospective cross-sectional study.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a variable course with unpredictable flares. Identifying predictors of these flares is essential for monitoring and timely hospital care. To characterize the prevalence of flares within the first five years of SLE diagnosis and determine the clinical and immunological characteristics associated with flare development among patients attending the Rheumatology Clinic at Tikur Anbesa Specialized Hospital (TASH) and Lancet General Hospital. A multicenter, cross-sectional study was conducted from May 2023 to November 2023 at TASH and Lancet General Hospital. The data was collected from electronic medical records and analyzed using SPSS version 26. Logistic regressions were used to determine factors associated with lupus flare. Most patients with SLE were female (95.4%). The most common clinical presentations were musculoskeletal (71.8%), cutaneous (55%), and constitutional (22%). Almost half (44.3%) of the patients had comorbidity illness. Positive ANA test was found in 96.5% of the patients, whereas only 55% had positive anti-dsDNA test. The prevalence of SLE flare in the first five years of SLE diagnosis was 38.9%, and most flares occurred within the first year of diagnosis. Patients with the following characteristics were more likely to have flare-ups: younger age at diagnosis (less than 25years old), initial presentation with vasculitis, renal flare, and being on low-dose prednisolone. The most common clinical presentations were musculoskeletal, dermatologic, and constitutional manifestations. Age < 25years at diagnosis, initial clinical presentation with renal manifestation, and being on low-dose prednisolone were predictors of SLE flare. Key Points • This study found a significant gender disparity, with 95% female. • Nearly 39% of patients experienced an SLE flare within the first five years of diagnosis. • Over three-quarters (77%) of flares occurred within the first year of diagnosis. • Age less than 25years, initial presentation with vasculitis, renal involvement, and being on low-dose prednisolone were identified as predictors of flares.

Pregnancy outcome predictors in systemic lupus erythematosus: a systematic review and meta-analysis

To enhance patient-tailored preconception risk assessment for women with systemic lupus erythematosus (SLE), knowledge on risk factors associated with adverse pregnancy outcomes is required. Therefore, we did a systematic review and meta-analysis to identify and provide unambiguous effect sizes of preconception predictors of pregnancy outcomes in women with SLE. In this systematic review and meta-analysis, we searched PubMed and Embase for studies reporting preconception predictors of pregnancy outcomes in women with SLE, from database inception to Aug 22, 2023. Studies were included if they presented original, quantitative data on pregnant women with SLE and reported on preconception risk factors on at least one of the outcomes as defined in the protocol. Studies were excluded if they had a sample size of less than 20 patients, were restricted to multiple pregnancies, had unclear timing of prognostication, or exclusively reported a composite outcome. Literature screening, data extraction, and risk-of-bias assessment (quality in prognostic studies tool) were done by two reviewers independently, in a blinded, standardised manner. The reported outcomes included livebirth, pre-eclampsia, small for gestational age, preterm birth, pregnancy loss before and after 20 weeks of gestation, and SLE flares. We computed pooled univariate odds ratios (ORs) and 95% CIs using a random effects model. We assessed heterogeneity using the I2 statistic and prediction intervals. This study is registered with PROSPERO, CRD42022344732. Of the 6705 unique articles identified, 72 (1·1%) were included in the meta-analysis, comprising 10 355 pregnancies in 8065 women with SLE. One potentially eligible study was retracted and therefore removed from our analysis. Previous lupus nephritis was associated with decreased livebirth probability (OR 0·62 [95% CI 0·47-0·81]; I2=0%), increased risk of preterm birth (2·00 [1·55-2·57]; I2=17%), and increased risk of pre-eclampsia (3·11 [2·35-4·12]; I2=0%). Chronic hypertension was associated with increased risk of disease flare (2·50 [1·74-3·58]; I2=0%), preterm birth (2·65 [1·87-3·77]; I2=0%), and pre-eclampsia (5·86 [3·41-10·06]; I2=33%). SLE disease activity at conception or preconception was associated with increased risk of preterm birth (2·91 [1·96-4·33]; I2=21%) and pre-eclampsia (2·32 [1·40-3·83]; I2=0%). Secondary antiphospholipid syndrome was associated with decreased livebirth probability (0·40 [0·27-0·58]; I2=0%), increased risk of pregnancy loss after 20 weeks of gestation (2·77 [1·44-5·31]; I2=0%), and increased risk of preterm birth (1·65 [1·29-2·11]; I2=0%). Across studies, risk-of-bias assessment suggested considerable bias in study attrition and confounding. We identified previous lupus nephritis, chronic hypertension, SLE disease activity before and at conception, and secondary antiphospholipid syndrome as predictors of adverse pregnancy outcomes in women with SLE. These findings contribute to an optimal patient-tailored risk assessment in preconception counselling. None.

Longitudinal analysis at pre- and post-flare of T peripheral helper and T follicular helper subsets in patients with systemic lupus erythematosus

ObjectiveWe focused to analyze the time-course changes at pre- and post-flare of T peripheral helper (Tph) cells and circulating T follicular helper (Tfh) cells in the blood of patients with systemic lupus erythematosus (SLE) with lupus low disease activity state (LLDAS) before flare. MethodsThis study included inactive (n = 29) and active (n = 55) patients with SLE. Tph subsets, Tfh subsets, CD11chi B cells, and plasma cells in the blood were determined by flow cytometry. The blood levels of cytokines including interferons (IFNs) were measured by electrochemiluminescence assay or cytokine beads array. ResultsActive SLE patients exhibited the increased frequency of Tph1, Tph2, Tfh1, and Tfh2 subsets when compared to inactive patients, but no clear changes in the other subsets. During the treatment with medications, Tph1, Tph2, and Tfh2 subsets were significantly reduced along with disease activity and Tph1 and Tph2 subsets were positively correlated with SLE disease activity index (SLEDAI). The time course analysis of patients at pre- and post-flare revealed that in the patients at LLDAS before flare, Tph subsets and Tfh subsets were relatively low levels. At the flare, Tph cells, particularly Tph1 and Tph2 subsets, were increased and correlated with SLEDAI. Furthermore, the blood levels of IFN-α2a, IFN-γ, and IFN-λ1 were low in the patients with LLDAS before flare but these IFNs, particularly IFN-λ1, were increased along with flare. ConclusionIncreased frequency of Tph1 and Tph2 subsets and elevated levels of serum IFN-λ1 are presumably critical for triggering of flare in SLE.

Improved Health Outcomes in Patients with Systemic Lupus Erythematosus Following Early Belimumab Initiation Without Prior Immunosuppressant Use: A Real-World Descriptive Study.

Patients with systemic lupus erythematosus (SLE) have variable treatment pathways, including antimalarials, glucocorticoids, immunosuppressants, and/or biologics. This study describes differences in clinical outcomes when initiating belimumab (BEL) before and after immunosuppressant use. This real-world, retrospective cohort study (GSK Study 217536) used de-identified administrative claims data from January 2015 to December 2022 in the Komodo Health Database. Adults with moderate/severe SLE initiating BEL (index date) were identified from January 2017 to May2022, allowing a ≥ 24-month baseline period. Patients were stratified into those initiating BEL before immunosuppressant use (no immunosuppressant use within 24months before index) and those initiating BEL after immunosuppressant use (one immunosuppressant used within 24months before index). Oral glucocorticoid (OGC) use, SLE flares, new organ damage, and all-cause healthcare resource utilization (HCRU) were analyzed descriptively over a 24-month follow-up. Baseline SLE severity was similar for patients initiating BEL before (n = 2295) versus after (n = 4114) immunosuppressant use (moderate, 83.1% vs 79.0%; severe, 16.8% vs 21.0%). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates and OGC use. Post-index, patients initiating BEL before versus after immunosuppressant use discontinued their OGC sooner (moderate baseline SLE, 4.5 vs 8.9months; severe baseline SLE, 6.2 vs 11.6months). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates per person-year at all time points (especially severe flare rates in patients with severe baseline SLE, 0.70 vs 1.48 through 24months post-index). Median time to new organ damage occurrence was longer in patients initiating BEL before versus after immunosuppressant use (moderate baseline SLE, 32.1 vs 26.7months; severe baseline SLE, 22.7 vs 21.6months). All-cause HCRU was similar between cohorts. These results suggest that patients initiating BEL before versus after immunosuppressant use had more favorable outcomes.

Cardiac Sarcoma Mimicking Libman-Sacks Endocarditis in a Patient with Systemic Lupus Erythematosus (SLE): A Case Report and Literature Review.

We present the case of a 39-year-old woman who was diagnosed with SLE and antiphospholipid antibodies 8 years ago. The chief manifestations of her disease included low-grade fever and polyarthritis. Eight months before presentation, she experienced symptoms attributed to a flare of SLE, leading to an increase in immunomodulatory treatment with no improvement. She presented to the emergency room with acute onset of dyspnea. Clubbing of her fingers and toes was noted. When questioned, she reported the onset of clubbing 5 months earlier. A CTA was performed to rule out pulmonary embolism, which was excluded, although it revealed a severely damaged mitral valve with severe insufficiency and a large mass on the valve, protruding into the left atrium. Antibiotics were started, with a working diagnosis of infectious endocarditis; however, the severe mitral valve dysfunction lead to emergency mitral valve replacement, revealing an organized thrombus. She was treated with anticoagulation, with a working diagnosis of Libman-Sacks endocarditis, with no improvement. Additional immunosuppression failed to improve her symptoms. Enlargement of the thrombotic mass and an increased gradient across the prosthetic mitral valve led to repeat surgery, culminating in a diagnosis of high-grade sarcoma within the left atrial mass. We further discuss cardiac sarcoma and describe the occurrence of clubbing in patients with sarcoma. This case highlights the importance of interdisciplinary collaboration and the need for vigilant monitoring in refractory cases, particularly when atypical presentations arise.

Intercurrent infection as a risk factor for disease flares in patients with systemic lupus erythematosus

ObjectiveTo determine whether intercurrent infections are a risk factor for subsequent disease flares in systemic lupus erythematosus (SLE).MethodsDemographic and clinical characteristics of 203 patients with SLE participating in the Amsterdam...

Acute Lupus Pneumonitis with Cytomegalovirus Co-infection in Patients with Lupus Nephritis

Introduction: Most patients with systemic lupus erythematosus (SLE) show signs of pulmonary involvement. The clinical manifestations of Lupus Pneumonitis are the similar to those of acute interstitial pneumonia. The use of cyclophosphamide in lupus nephritis (LN) is associated with high CMV titers. Ganciclovir is the main choice of therapy for CMV pneumonia infection. Case presentation: A 19-year-old female with previous history of lupus nephritis presented with worsening dyspnea, productive cough with yellowish sputum and hemoptysis. Following physical, laboratory and radiological examinations, the patient was diagnosed with acute lupus pneumonitis, with a differential diagnosis of pneumonia infection. During treatment in the intensive care unit (ICU), she was put on ventilator and received routine hemodialysis due to pulmonary edema. She was given intravenous antibiotics before the culture results came out, but there was no clinical improvement. Once the culture results returned negative, the antibiotics were discontinued and IV pulse methylprednisolone was started. There was significant clinical, radiological, and laboratory improvements. After discharge, the patient experienced hemoptysis again due to CMV pneumonia infection and was given ganciclovir therapy with satisfactory results. Conclusion: In patients with advanced LN and pulmonary involvement, distinguishing between infection and SLE flares may be challenging, which can cause dilemma in diagnosis and treatment decisions. Adequate oxygenation with ventilator, hemodialysis, and administration of ganciclovir and mycophenolic acid provides significant improvements in patient care.

Clinical features of flare in Japanese patients with new-onset SLE and risk factors for SLE flare in daily clinical practice: a single-center cohort study

This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan–Meier’s curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan–Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice.

Healthcare resource utilization and costs in patients with a newly confirmed diagnosis of lupus nephritis in the United States over a 5-year follow-up period

BackgroundWe aimed to describe healthcare resource utilization (HCRU) and healthcare costs in patients with newly confirmed lupus nephritis (LN) in the United States over a 5-year follow-up period.MethodsThis retrospective, longitudinal cohort study (GSK Study 214102) utilized administrative claims data to identify individuals with a newly confirmed diagnosis of LN between August 01, 2011, and July 31, 2018, based on LN-specific International Classification of Diseases diagnosis codes. Index was the date of first LN-related diagnosis code claim. HCRU, healthcare costs, and incidence of systemic lupus erythematosus (SLE) flares were reported annually among eligible patients with at least 5 years continuous enrollment post-index.ResultsOf 2,159 patients with a newly confirmed diagnosis of LN meeting inclusion and exclusion criteria, 335 had at least 5 years continuous enrollment post-index. HCRU was greatest in the first year post-LN diagnosis across all categories (inpatient admission, emergency room [ER] visits, ambulatory visits, and pharmacy use), and trended lower, though remained substantial, in the 5-year follow-up period. Among patients with LN and HCRU, the mean (standard deviation [SD]) number of ER visits and inpatient admissions were 3.7 (4.6) and 1.8 (1.5), respectively, in Year 1, which generally remained stable in Years 2–5; the mean (SD) number of ambulatory visits and pharmacy fills were 35.8 (25.1) and 62.9 (43.8), respectively, in Year 1, and remained similar for Years 2–5. Most patients (≥ 91.6%) had ≥ 1 SLE flare in each of the 5 years of follow-up. The proportion of patients who experienced a severe SLE flare was higher in Year 1 (31.6%) than subsequent years (14.3–18.5%). Total costs (medical and pharmacy; mean [SD]) were higher in Year 1 ($44,205 [71,532]) than subsequent years ($29,444 [52,310]–$32,222 [58,216]), driven mainly by inpatient admissions (Year 1: $21,181 [58,886]; subsequent years: $7,406 [23,331]–$9,389 [29,283]).ConclusionsPatients with a newly confirmed diagnosis of LN have substantial HCRU and healthcare costs, particularly in the year post-diagnosis, largely driven by inpatient costs. This highlights the need for improved disease management to prevent renal damage, improve patient outcomes, and reduce costs among patients with renal involvement.

#971 Effects of arsenic trioxide on MMP9/IL-17A expression in lupus nephritis—results from bioinformatics analysis and in vitro studies

Abstract Background and Aims Previous research has indicated that ATO treatment at low doses may decrease the likelihood of flares in active systemic lupus erythematosus (SLE) patients, but the pharmacological mechanisms of such effect have not been studied. Method Machine learning and network pharmacology analysis were employed to explore the potential targets from differentially expressed genes (DEGs) of human SLE and LN peripheral blood mononuclear cells (PBMCs) microarray datasets and pharmacological databases. GO and KEGG analyses were performed, and the protein-protein interaction (PPI) network was constructed. The association of these characteristic genes and immune cells were further examined and validated. Results Three machine learning models (RF, SVM, and XGB) were utilized to identify five immunoregulatory genes in SLE among twelve intersection DEGs. Among these genes, MMP9 exhibited the highest ROC AUC (0.92) in predicting disease development. KEGG analysis revealed significant associations with the IL-17 signaling pathway (p = 1.67E-18). Furthermore, ssGSEA analysis indicated positive correlations between MMP9 and macrophages (correlation coefficient 0.88) as well as neutrophils (correlation coefficient 0.66). In vitro treatment of PBMCs from lupus nephritis (LN) patients with ATO resulted in downregulation of MMP9 and IL-17A, validating our bioinformatics findings. Conclusion ATO has the potential to mitigate the MMP/IL-17A pathways in PBMCs in LN patients, and hence maybe a promising and innovative therapeutic alternative.

#2172 Maternal, obstetric and perinatal outcomes in pregnant women with lupus nephritis: experience of a tertiary center

Abstract Background and Aims Pregnant patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) are at particular risk for unfavourable maternal, obstetric and perinatal outcomes, especially if the disease is active. Thus, it is of paramount importance that LN patients have preconceptional counseling in order to optimize care and define the best moment to conceive. Method Observational retrospective study based on the review of medical records of pregnant women with lupus nephritis surveilled at our multidisciplinary maternal-fetal clinic from 2011 to 2023. Results We evaluated 26 gestations in 24 patients. Mean age was 30,8 years (19-40), 21 women were Caucasian, 2 black African, 1 Asian; 10/24 were nulliparous and 6/24 had chronic hypertension (HTUN). Mean baseline SCr was 0,79 mg/dl (0.5-3.5), baseline proteinuria &amp;gt; 1 g/day or &amp;lt;0,5 g/day was present in 3/26 and 22/26 gestations, respectively. Chronic kidney disease (CKD) stage 2, 3 and 5 was present in 1, 2 and 1 gestation respectively; 5/24 patients were APL positive; positive dsDNA and complement consumption at baseline were present in 4/26 and 12/26 gestations, with most patients previously having class IV LN (15/23). Active lupus nephritis during pregnancy occurred in 3 patients: 2 were submitted to medical termination of pregnancy (due to severe pulmonary HTN and renal function deterioration) and 1 was successfully treated with tacrolimus, azathioprine and prednisolone from week 28, and biopsied postpartum. Exposure to teratogenic therapy during the 1st trimester occurred in 3/26 gestations with a mean exposure of 8,5 weeks. Worsening kidney function occurred in 3/24 patients due to PE (1/26 CKD stage 3)/LN (1/26 stage CKD3)/pregnancy hyperfiltration (1/26 CKD stage CKD5), with partial and full renal recovery in 2 CKD stage 3 patients and dialysis initiation in the CKD stage 5 patient at 19 weeks (urea levels &amp;gt; 100 mg/dL). De novo proteinuria occurred in 3/24 patients (due to LN) and worsening proteinuria in 6/24 patients (PE 2/6; pregnancy hyperfiltration 4/6). De novo or worsening HTN occurred in 3/26 gestations. Immunosuppression during pregnancy consisted on azathioprine, prednisolone and hydroxychloroquine. SLE Flares occurred in 7/26 (27%) patients, with minor relapses in 4/6 gestations (hepatic, skin and articular involvement) and major renal flares in 3/6 gestations. All renal relapses occurred in patients with no preconception counseling nor immunosuppressive therapy. PE occurred in 2/26 (7,6%) gestations. Abortion occurred in 6/26 pregnancies (3 spontaneous abortions, 2MTP, 1 voluntary interruption). Cesarean (C) rate was 34,6%. Mean gestation age at delivery was 37±3 (28-40) weeks. Mean birth weight was 2789±859 mg (800-4175), 4 newborns were low birth weight (&amp;lt;2500 g). Apgar scores at 5/10 minutes were 10/10, respectively. Neonatal intensive care (NICU) was needed in 5 newborns. Conclusion In our series of SLE patients with LN, worsening kidney function only occurred in patients with advanced CDK, and renal flares in patients without preconceptional counseling nor immunosuppressive therapy, which underlines the importance of careful pregnancy planning. One patient with proliferative LN was successfully treated with tacrolimus associated to azathioprine and prednisolone during pregnancy, being a valuable therapeutic option in these situations. Although SLE patients with LN can have safe pregnancies, we still found an increased incidence of maternal, obstetric and perinatal complications, namely HTN, PE, C, low birth weight and the need of NICU.