Systemic Lupus Erythematosus Flare Research Articles

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.

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.

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.

Uncommon toxic epidermal necrolysis -like presentation of cutaneous lupus erythematosus: A series of 6 cases.

TEN like Lupus erythematosus is an uncommon life-threatening variant of Lupus erythematosus. It is usually associated with flares of systemic lupus erythematosus and also because of widespread skin erosions, it can cause acute skin failure. It is often confused with drug induced TEN, however the management of both the diseases is different and hence correct diagnosis becomes crucial. In this study we aimed to assess the clinical characteristics and outcome of TEN like LE in the Indian population. All patients satisfying ACR/EULAR 2019 criteria for SLE and clinically diagnosed with TEN like LE were retrospectively reviewed. A total of 6 patients were identified. All patients were female. Except 1 patient who presented de-novo, the others had pre-existing symptoms of connective tissue disease. Half of the patients had palmoplantar involvement. Mucosal involvement was only mild. Majority had systemic involvement in the form of nephritis followed by arthralgia, autoimmune hepatitis and autoimmune hemolytic anemia.

P022 Unmasking the storm: hemophagocytic lymphohistiocytosis in systemic lupus erythematosus - a case series

Abstract Background/Aims Hemophagocytic lymphohistiocytosis (HLH), a critical illness of uncontrolled immunological activity and hyperinflammation, manifests as primary/familial or secondary form. Secondary HLH can be of multi-faceted etiology including infections, cancer, autoimmune and immunodeficiencies. HLH in context of systemic lupus erythematosus (SLE) is a rare entity and mirrors the clinical picture of SLE flare, adding to the diagnostic dilemma. Methods Our objective is to consider HLH as a key differential in unidentified autoimmune diseases. We present a trio of cases of undiagnosed SLE manifesting as HLH. Results A 13-year-old male presented with fever, rash, oral ulcers, and jaundice for a month with passage of dark coloured urine for last seven days. On examination, he had generalized lymphadenopathy, erythematous maculopapular rashes, palpable purpura, non-scarring alopecia, and hepatosplenomegaly. The labs revealed pancytopenia (Hb 9.8g/dL, WBC 2000/mm3, Platelets 23000/mm3), deranged creatinine (1.6mg/dL), transaminitis and hyperbilirubinemia, hyper-ferritinemia (2420µg/dL), hypertriglyceridemia (280mg/dL), hypofibrinogenemia (142mg/dL), and nephrotic range proteinuria (3.7g/24h). Diagnosis of SLE was confirmed by high titres of antinuclear antibody (ANA) and anti-double stranded DNA (dsDNA) and anti-Smith positivity. Renal biopsy showed class II lupus nephritis and acute tubular necrosis. Bone marrow biopsy revealed hemophagocytosis and the diagnosis of SLE complicated by HLH was made. A 16-year-old girl presented with fever and headache for three weeks, worsening over last ten days with irritable behaviour for one day, and respiratory distress that necessitated endotracheal intubation. The presence of pancytopenia (9.1/1940/41000), transamintis, hyper-ferritinemia (4040µg/dL), hypertriglyceridemia (250mg/dL), and low fibrinogen (133mg/dL) in laboratory evaluation raised a compelling suspicion of HLH confirmed by hemophagocytosis on marrow biopsy. Cerebrospinal fluid analysis was unremarkable, however MRI detected features of vasculitis with vasculitic infarcts. Direct Coomb’s test was positive. Autoimmune profiling unveiled positive results for ANA, anti-dsDNA, and anti-Smith antibodies consistent with SLE. A 21-year-old female presented with fever and arthralgias for two months. Investigations were suggestive of pancytopenia (7/1050/36000), raised ESR (126mm/hr) and CRP (54 mg/dL), elevated ferritin (4320 µg/dL), lactate dehydrogenase (1068U/L) and triglycerides (439mg/dL). The marrow biopsy was negative for hemophagocytosis while her soluble interleukin - 2 receptor levels were elevated (2740 U/ml). ANA and dsDNA were positive in significant titres, complement levels were low and Coombs test was positive, thereby confirming the primary diagnosis of SLE. All patients received methylprednisolone pulse along with cyclophosphamide in case 1 and IVIG in case 2 and 3, resulting in remarkable improvement. Conclusion With a prevalence of 0.9-4.6%, HLH secondary to SLE is an uncommon entity. The diagnosis of HLH related to SLE is challenging since the symptoms overlap, however findings of hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia favour HLH over SLE. Once HLH is proven, immunological testing for SLE is warranted to prevent diagnostic delay. Early treatment is needed to combat such a fulminant life-threatening illness. Disclosure R. Mishra: None. A. Rohatgi: None. S. Anuradha: None. N. Kumar: None. S. Singhla: None. S.T. Mathews: None. S. Kumar: None. P. Gautam: None.

Comparison of Attainment and Protective Effects of Lupus Low Disease Activity State in Patients With Newly Diagnosed Versus Established Systemic Lupus Erythematosus.

To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE). Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare. Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up. LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).

Recent findings about antimalarials in cutaneous lupus erythematosus: What dermatologists should know.

Antimalarials (AMs), particularly hydroxychloroquine (HCQ) and chloroquine (CQ), are the cornerstone of the treatment for both systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). HCQ and CQ are recommended as first-line oral agents in all CLE guidelines. Initially thought to have potential therapeutic effects against COVID-19, HCQ has drawn significant attention in recent years, highlighting concerns over its potential toxicity among patients and physicians. This review aims to consolidate current evidence on the efficacy of AMs in CLE. Our focus will be on optimizing therapeutic strategies, such as switching from HCQ to CQ, adding quinacrine to either HCQ or CQ, or adjusting HCQ dose based on blood concentration. Additionally, we will explore the potential for HCQ dose reduction or discontinuation in cases of CLE or SLE remission. Our review will focus on the existing evidence regarding adverse events linked to AM usage, with a specific emphasis on severe events and those of particular interest to dermatologists. Last, we will discuss the optimal HCQ dose and the balance between preventing CLE or SLE flares and minimizing toxicity.

Different Immunologic Profiles Are Associated With Distinct Clinical Phenotypes in Longitudinally Observed Patients With Systemic Lupus Erythematosus.

The aim of this study was to determine the immunologic profile associated with disease flares in patients with systemic lupus erythematosus (SLE) and to investigate the clinical significance of any differences observed between patients during and following a flare. Multiparameter flow cytometry was used to examine 47 immune populations within the peripheral blood of 16 healthy controls, 25 patients with clinically quiescent SLE, and 46 patients with SLE experiencing a flare at baseline and at 6- and 12-month follow-up visits. Unsupervised clustering was used to identify patients with similar immune profiles and to track changes over time. Parametric or nonparametric statistics were used when appropriate to assess the association of cellular phenotypes with clinical and laboratory parameters. Five clusters of patients were identified that variably contained patients with active and quiescent SLE, and that had distinct clinical phenotypes. Patients characterized by increased T peripheral helper, activated B, and age-associated B cells were the most likely to be flaring at baseline, as well as the most likely to remain active or flare over the subsequent year if they acquired or retained this phenotype at follow-up. In contrast, patients who had increased T helper (Th) cells in the absence of B cell changes, or who had increased Th1 cells and innate immune populations, mostly developed quiescent SLE on follow-up. A significant proportion of patients with SLE had depletion of many immune populations at flare and only showed increases in these populations post-flare. Cellular phenotyping of patients with SLE reveals several distinct immunologic profiles that may help to stratify patients with regard to prognosis and treatment.

The Impact of Systemic Lupus Erythematosus Flares on Clinical and Economic Outcomes: The CHAMOMILE Claims Database Study in Germany.

CHAMOMILE (CHaracteristics and impact of flares on clinicAl and econoMic OutcoMes In patients with systemic Lupus Erythematosus [SLE]) examined how flares in the year of SLE diagnosis impact future disease activity and damage, productivity, healthcare resource utilization (HCRU), and costs in patients with SLE in Germany. CHAMOMILE was a retrospective cohort study of adults with an SLE diagnosis in the German Sickness Fund Database from 1July 2010 to 31December 2013. Patients were classified according to their greatest flare severity during the baseline year (none, mild, or moderate/severe). The number and severity of flares were assessed annually over 5-8.5 follow-up years, along with SLE organ/system damage, treatments, work disability, and HCRU metrics. Of 2088 patients (84.6% female; mean age [standard deviation] 51.4 [16.1] years; mean follow-up 6.8 [2.1] years), 34.3% (n = 716) were flare-free, 29.8% (n = 622) had mild flares, and 35.9% (n = 750) had moderate/severe flares at baseline. Baseline flare severity was related to future flares: rates during follow-up were higher in patients with moderate/severe baseline flares compared with those with mild or no baseline flares (89.6 vs 78.5 and 44.2 flares/100 patient years, respectively). Overall, 80.2% (n = 1675) of patients received glucocorticoids at least once during baseline and follow-up. Patients' HCRU was generally greatest in their baseline year. Costs were highest in patients with moderate/severe baseline flares. Baseline flare severity provided insight into a patient's disease course and the clinical and economic burden of SLE over time, highlighting the ramifications of uncontrolled disease for patients with SLE.

A 12-month follow-up study of patients with systemic lupus erythematosus after immunization against SARS-CoV-2.

To identify all post-BNT162b2 vaccination (BioNTech and Pfizer) events during the ensuing 12months in patients with systemic lupus erythematosus (SLE) from the Immuno-Rheumatology Department at Cayetano Heredia Hospital's cohort, Lima, Perú. A 12-month follow-up study was conducted from the first dose of immunization with the BNT162b2 vaccine, which was given between May and June 2021, to SLE patients from this cohort. The initial population was constituted by 100 patients (100 patients received the 1st dose, 90 the 2nd dose, and 85 the 3rd dose of this vaccine); 33 patients presented a SLE reactivation (flare), 9% (9/100) post 1st dose, 26.6% (24/90) post 2nd dose, and 16.4% (14/85) post 3rd dose. The most common types of flare were articular (26) and renal (14) with 5/33 (15.1%) requiring hospitalization for flare management. A negative association with flare occurrence was found between the use of hydroxychloroquine RR 0.43 (0.21-0.85) and the opposite was the case for azathioprine RR 2.70 (1.39-5.25). During follow-up, 26 patients developed SARS-CoV-2 infection of whom three required hospitalization, one of whom died. 33 of 100 SLE patients immunized with BNT162b2 vaccine against SARS-CoV-2, presented SLE flares (47 episodes in total); 5 of these patients required in-hospital management and all fully recovered; 26 patients had SARS-CoV-2 infection; three required hospitalization, one died.

Systemic Lupus Erythematosus: How Machine Learning Can Help Distinguish between Infections and Flares.

Systemic Lupus Erythematosus (SLE) is a multifaceted autoimmune ailment that impacts multiple bodily systems and manifests with varied clinical manifestations. Early detection is considered the most effective way to save patients' lives, but detecting severe SLE activity in its early stages is proving to be a formidable challenge. Consequently, this work advocates the use of Machine Learning (ML) algorithms for the diagnosis of SLE flares in the context of infections. In the pursuit of this research, the Random Forest (RF) method has been employed due to its performance attributes. With RF, our objective is to uncover patterns within the patient data. Multiple ML techniques have been scrutinized within this investigation. The proposed system exhibited around a 7.49% enhancement in accuracy when compared to k-Nearest Neighbors (KNN) algorithm. In contrast, the Support Vector Machine (SVM), Binary Linear Discriminant Analysis (BLDA), Decision Trees (DT) and Linear Regression (LR) methods demonstrated inferior performance, with respective values around 81%, 78%, 84% and 69%. It is noteworthy that the proposed method displayed a superior area under the curve (AUC) and balanced accuracy (both around 94%) in comparison to other ML approaches. These outcomes underscore the feasibility of crafting an automated diagnostic support method for SLE patients grounded in ML systems.

Predictors of renal flares in systemic lupus erythematosus: a post-hoc analysis of four phase III clinical trials of belimumab.

To identify predictors of renal flares in patients with SLE treated for active extra-renal disease. Data from four clinical trials of belimumab in SLE (BLISS-52, NCT00424476; BLISS-76, NCT00410384; BLISS-NEA, NCT01345253; BLISS-SC, NCT01484496) were used. Patients were assigned to belimumab or placebo on top of standard therapy. We investigated the performance of predictors of renal flares through 52-76 weeks using proportional hazards regression analysis. Of 3225 participants, 192 developed at least one renal flare during follow-up, with the first occurring after a median time of 197 days. Current/former renal involvement (HR: 15.4; 95% CI: 8.3-28.2; p< 0.001), low serum albumin levels (HR 0.9; 95% CI: 0.8-0.9; p< 0.001), proteinuria (HR: 1.6; 95% CI: 1.5-1.7; p< 0.001), and low C3 levels (HR: 2.9; 95% CI: 2.1-4.1; p< 0.001) at baseline appeared robust determinants of renal flares. Anti-dsDNA positivity yielded an increased hazard for renal flares (HR: 2.1; 95% CI: 1.4-3.2; p< 0.001), which attenuated after adjustments. Anti-Sm positivity was associated with renal flares in the placebo (HR: 3.7; 95% CI: 2.0-6.9; p< 0.001) but not in the belimumab subgroup, whereas anti-ribosomal P positivity was associated with renal flares in the belimumab subgroup only (HR: 2.8; 95% CI: 1.5-5.0; p= 0.001). A history of renal involvement, high baseline proteinuria, hypoalbuminaemia, and C3 consumption were robust determinants of impending renal flares. Beyond anti-dsDNA, anti-Sm and anti-ribosomal P protein antibody positivity may have value in surveillance of renal SLE.

Predictors of flare-related inpatient or emergency department stay in systemic lupus erythematosus: A real-world analysis of Medicaid claims in the United States.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem inflammation. Medical management of SLE is based on reducing inflammation and tissue damage in the affected organs; however, medications used to treat SLE have been found to contribute to additional organ damage. Therefore, finding new ways to predict and prevent flares that require an inpatient (IP) stay or emergency department (ED) visit is critical for reducing the clinical and economic burden in patients with SLE. To identify risk factors of SLE flares requiring an IP/ED visit among a Medicaid-insured population with SLE. This retrospective study included patients from the Merative MarketScan Medicaid database (2013-2019). To capture patients at all stages of their SLE journey, all SLE claims for a patient were captured, and the index date was randomly selected among those claims that were at least 12 months after the first evidence of SLE. Patients were required to be continuously enrolled 1-year pre-index (year 1) and post-index (year 2). Demographics, clinical characteristics, and health care use and costs were measured in year 1, and flares requiring an IP/ED visit were identified in year 2 using the Garris algorithm. Multivariable logistic regression and classification and regression tree (CART) modeling were used to identify year 1 predictors and combination of factors, respectively, associated with flares-related IP/ED visits. Of the 8,083 patients included in the study, 37.6% of patients (n = 3,039) had a flare. Logistic regression identified ED visits in year 1 as one of the strongest predictors of flares-related IP/ED visits in year 2 (odds ratio = 2.19 [95% CI = 1.93-2.49]). SLE treatment progression to biologics (0.54 [0.42-0.70]) was the strongest predictor of decreased odds. Other strong predictors included other neurological disorders (1.63 [1.43-1.87]), Black race (1.49 [1.32-1.68]), chronic kidney disease/renal failure (1.35 [1.10-1.66]), and opioid use (1.30 [1.17-1.45]). CART modeling identified patients with an ED visit, an IP admission, and a diagnosis of Elixhauser Comorbidity Index-defined other neurological disorders in year 1 as having the highest probability of a flare-related IP/ED visit in year 2 (probability = 0.708), whereas patients without an ED visit had the lowest probability (probability = 0.185). Patients with the highest risk of a flare that required an IP/ED visit were those with a prior ED visit, IP admission, and other neurological disorders. Modeling also identified patients with prior opioid use, Black patients, and patients without SLE medications as subgroups with a high risk of a flare requiring an IP/ED visit.

Characteristics of patients with initial diagnosis of systemic lupus erythematosus in emergency department and their outcomes: a retrospective single-center study.

This study aims to investigate the characteristics of patients with an initial diagnosis of systemic lupus erythematosus (SLE) in an emergency department (ED) and their outcomes. A total of 147 SLE patients (119 females and 28 males, mean age 26 ± 19 years) who visited the ED of the Peking University People's Hospital between January 2017 and June 2022 were enrolled in the study. Data on demographic information, clinical characteristics, comorbidities, therapy, and outcomes were collected. Most patients visit ED because of symptoms related to SLE (74.8%, 110/147). The remaining 37 patients (25.2%) visited ED due to infection (43.2%, 16/37), gastrointestinal bleeding (10.8%, 4/37), coronary heart or cerebrovascular disease (18.9%, 7/37), macrophage activation syndrome or thrombotic microangiopathy (18.9%, 7/37), leukemia (5.4%, 2/37), and hepatic encephalopathy (2.7%, 1/37). Of the patients, 54.4% (80/147) were first diagnosed with SLE at the time of their ED visit. Thrombocytopenia events occurred significantly more frequently in this group of patients (OR 3.664, 95% CI 1.586-8.464, p = 0.002). Pulse steroid therapy was administered to 32.5% (26/80) of the patients with an initial diagnosis of SLE, and 26.3% (21/80) of these patients also received IVIG therapy during their ED visit. SLEDAI scores were significantly decreased after 6 months of therapy. The rate of mortality was 6.8% (10/147) in the 6-month follow-up period, and all the ten deaths happened in patients with disease-established SLE. The main causes of death were infections (two patients) and SLE flare (four patients). Understanding disease patterns can contribute to physicians providing accurate diagnosis and efficient care for SLE patients in ED. Key Points • Systemic lupus erythematosus, a complex autoimmune disorder, can have either a chronic or a relapsing and remitting disease course. The disease can involve acute events or severe comorbidities, and frequent visits to the emergency department (ED) are inevitable. • It is essential to better understand which comorbidities can lead to emergency department visits. Accurate clinical diagnosis and appropriate interventions from ED physicians can have a strong impact on the prognosis of the disease. • Hematologic compromise attributed to SLE flare is the most common reason for ED visits. Owing to aggressive treatments, the clinical outcomes in patients with initial diagnosis of SLE have improved notably. • Our study highlights that early recognition and appropriate management of SLE-related conditions and other comorbidity in ED are crucial.