Lupus最新文献

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disorder that affects various organs and follows a pattern of remission and relapse. Hydroxychloroquine (HCQ), an antimalarial drug, has recently become widely used in pregnant women with SLE due to its multi-level immune anti-inflammatory mechanisms and potential endothelial protective and thromboprophylaxis properties. While several studies have evaluated the impact of HCQ on SLE activity and the occurrence of neonatal lupus, its effects on improving early delivery, preeclampsia, and intrauterine growth restriction (IUGR) remain controversial.ObjectiveThis study aims to determine the effect of HCQ on feto-maternal outcomes among pregnant women with SLE.MethodologyIt is a retrospective cohort study over the past 25 years at Aga Khan Hospital, Karachi. The patients were divided into two groups. HCQ group had been taking HCQ throughout pregnancy. Non-HCQ group hadn't been using HCQ. All statistical analysis was performed using SPSS version 19.0. For all tests, p ≤ .05 was considered statistically significant.ResultsA total of 125 pregnant women with SLE were reviewed. The majority had conception in the remission period. There were 7 (20.6%) babies with fetal heart block in the non-HCQ group. The overall flare-up of disease was found in 68.8% (86/125), mostly in the third trimester. Positive anticardiolipin IgG antibodies were considerably higher in HCQ groups (47.25% vs 26.47%; p = .036).ConclusionOur study findings suggest that maintaining disease remission prior to conception and continuing HCQ therapy during pregnancy may be associated with improved maternal and fetal outcomes, though the observed association with fetal heart block warrants cautious interpretation due to small numbers.

ObjectiveCentral serous chorioretinopathy (CSC) complicating lupus nephritis (LN) may arise from two distinct pathways: uncontrolled systemic inflammation (activity-associated CSC) or as an iatrogenic complication of therapy (glucocorticoid-induced CSC). This study aims to propose a clinically actionable framework for differentiating these entities and guide trigger-specific treatment selection.MethodsWe present a novel case of glucocorticoid (GC)-induced CSC successfully treated with a GC-free belimumab-tacrolimus regimen. A case report integrated with a review of the literature (PubMed, Embase, Web of Science, until May 2024) was conducted to identify all reported cases of concurrent LN and CSC. Cases were stratified by presumed CSC trigger, and treatment outcomes were analyzed.ResultsFour cases, including our index case, were analyzed. Two cases of activity-associated CSC (no recent GC exposure) achieved dual remission with aggressive GC-based immunosuppression. Two cases of GC-induced CSC (onset post-GC initiation) only achieved CSC remission after implementing GC-sparing strategies (GC taper to ≤5 mg/d or cessation). A treatment-trigger mismatch (using high-dose GC for GC-induced CSC) was associated with worsened ophthalmological outcomes.ConclusionThese findings support a dichotomous pathogenesis model for CSC in LN. Correctly classifying CSC as activity-associated or glucocorticoid-induced is the critical first step in management. This distinction informs opposing therapeutic strategies: standard GC-based immunosuppression is appropriate for the former, while prompt initiation of GC-sparing therapy is imperative for the latter. This proposed framework offers a path to resolve the longstanding therapeutic paradox in this complex clinical scenario.

Background and ObjectivesPulmonary diseases (PD) are common in Systemic Lupus Erythematosus (SLE) and associated with increased mortality and decreased health-related quality of life, but no study has so far addressed PD in newly diagnosed patients with SLE. Our objectives were among newly diagnosed patients with SLE to investigate: Primarily, if PD and subtypes of PD are present, and secondarily characterise the patients by means of (i) lung physiology, (ii) radiology, (iii) thoracic ultrasound (TUS) and diaphragmatic ultrasound (DUS).MethodsPatients newly diagnosed with SLE from 1st July 2023 to 31st July 2024 at Odense University Hospital, Odense, Denmark, underwent a dedicated clinical evaluation for PD, including pulmonary function tests (PFT), chest high-resolution computed tomography or computed tomography scan alongside with TUS and DUS. Subsequently, PD were diagnosed, and subtype was categorised on a multidisciplinary discussion.ResultsTen participants were included in average 3 months after SLE diagnosis, and six out of ten had PD. PD included one case of shrinking lung syndrome (SLS) and two cases of interstitial lung disease. All participants exhibited at least one abnormal PFT measure, with some showing severely reduced pulmonary function. TUS was associated with diseases of the lung parenchyma and pleura and DUS with SLS.ConclusionWe found PD among newly diagnosed patients with SLE and in some cases associated with severely affected pulmonary function. TUS and DUS may contribute with information in diagnosing SLE related PD, but further studies are needed.

ObjectiveTo evaluate whether hydroxychloroquine (HCQ) dose reduction (2-3 mg/kg/day) sustain lipoprotein levels achieved with higher doses of 2016-American Academy of Ophthalmology (2016-AAO) in stable lupus nephritis (LN) patients.MethodsForty-seven consecutive stable LN patients using HCQ 2016-AAO recommended dose for ≥6 months were enrolled and assigned to one of two groups: Reduced HCQ group (n = 21):LN patients who, upon inclusion, reduced 2016-AAO dose (2-3 mg/kg/day); and Maintenance HCQ group (n = 26):LN patients who continued on the standard 2016-AAO recommended HCQ dose (4.0-5.5 mg/kg actual body weight, maximum 400 mg/day) throughout 12-month study period. Blood HCQ levels, lipid profile and SLE parameters (including SLEDAI-2K) were assessed at baseline, 3 and 12-month.ResultsBaseline demographics, comorbidities and disease parameters were similar among groups (p > .05). Initial blood levels of Reduced HCQ group were 1219.4 (1041.7-1926.6)ng/mL and a progressive significant decrease were identified after 3 and 12 months [651.2 (538.4-832.6)vs.468.8 (228.4-925.6)ng/mL, p < .001]. Maintenance HCQ group had no changes in HCQ levels during the study [1179.7 (905.5-1607.3)vs.1026.2 (710.5-1345.8)vs.907.9 (663.9-1304.2)ng/mL, p = .158]. No changes were observed on the longitudinal total cholesterol levels of Reduced HCQ [166 (113-198)vs.153 (85-192)vs.150 (90-231)mg/dL, p = .964] and Maintenance HCQ [155 (114-244)vs.154 (122-210)vs.155 (112-213)mg/dL, p = .395]. LDL cholesterol levels of Reduced HCQ [91 (52-163)vs.83 (41-136vs.87 (47-165)mg/dL, p = .917] and Maintenance HCQ [79 (36-114)vs.76.5 (33-111)vs.75.5 (63-131)mg/dL, p = .412] remained similar. Other lipoprotein levels remained stable during 1 year of study.ConclusionThis is the first study to show that reducing HCQ to 2-3 mg/kg/day preserves lipid stability over 12 months in stable lupus nephritis patients.

PurposeTo describe ocular findings, including dry eye disease (DED) and evaluation of hydroxychloroquine (HCQ) retinal toxicity, in Juvenile Systemic Lupus Erythematosus (JSLE) patients followed in a Brazilian referral tertiary-care center.MethodsThis cross-sectional study included 46 JSLE patients under 18 years of age, consecutively recruited between 2020 and 2023, from two university centers. Ophthalmological evaluations included best-corrected visual acuity, tear film break-up time (BUT), Schirmer test, anterior biomicroscopy with fluorescein staining using van Bijsterveld scores, applanation tonometry, fundus examination, and Spectral-Domain Optical Coherence Tomography (SD-OCT). DED was defined using the 2006 Japanese Dry Eye Society criteria and the ocular Sjögren's syndrome criteria for dry eye. Associations between clinical, laboratory, and ocular findings were analyzed.ResultsOf the 46 patients (84.8% female; median age: 10 years), 76.1% met DED criteria, with 21.7% showing Schirmer test abnormalities (<10 mm). BUT <5 seconds was identified in 76%, and 45.65% had abnormal fluorescein staining. Only 8.7% reported symptoms of dry eye. No significant retinal abnormalities were detected on SD-OCT related to HCQ toxicity. The median HCQ cumulative dose was 204 g and the median time of its use was 2 years. A significant association between mycophenolate use and DED was identified (p = .041). No correlation was found between DED and antibody levels, complement levels, or corticosteroid use.ConclusionDED is highly prevalent and frequently asymptomatic in pediatric JSLE patients, emphasizing the need for routine ophthalmologic evaluations. The absence of SD-OCT abnormalities in this cohort aligns with low HCQ exposure, but further studies are needed to validate current adult-based screening guidelines in children.

Background: Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are complex autoimmune diseases with the potential to affect multiple organ systems and significantly impact quality of life. In the Middle East and North Africa (MENA), the burden of these conditions is amplified by a combination of genetic predisposition, environmental exposures, and socio-economic factors that shape both presentation and outcomes. High consanguinity rates, high ultraviolet exposure, infections, and lifestyle factors contribute to earlier onset and more aggressive disease, with lupus nephritis affecting up to 60% of patients. APS adds an additional layer of complexity through thrombotic events and pregnancy complications. Purpose: This review brings together current knowledge on the epidemiology, clinical patterns, and management challenges of SLE and APS across the region. Results: While individual country reports exist, the lack of large-scale registries limits our ability to fully define disease prevalence and outcomes. Delayed diagnosis, shortages of rheumatology specialists, and unequal access to advanced diagnostics and biologic therapies remain persistent barriers. In some low-resource or conflict-affected settings, even basic immunosuppressive medications are inconsistently available. The financial impact is substantial, driven by hospitalizations, medications, and loss of productivity, with many patients facing significant out-of-pocket costs. Recent advances, including biologics such as belimumab and anifrolumab, offer opportunities to improve outcomes but are not equitably accessible across the region. Conclusions: Moving forward, investment in healthcare infrastructure, training, and culturally appropriate patient education will be essential. Establishing regional registries, expanding research into genetic and environmental risk factors, and developing locally relevant management strategies are critical next steps. By addressing these gaps through coordinated action between policymakers, healthcare providers, researchers, and patient communities, it is possible to reduce the disparities in care and improve survival, function, and quality of life for people living with SLE and APS in the MENA region.

ObjectiveMembranous nephropathy can be categorised into idiopathic membranous nephropathy (iMN) and secondary membranous nephropathy (sMN). However, it should be noted that a subset of patients initially diagnosed with iMN may develop secondary etiologies during longitudinal follow-up, even in the absence of systemic manifestations at initial presentation.MethodsThis is a single-center retrospective analysis. From January 2017 to April 2024, patients who were diagnosed with iMN at the time of their initial renal biopsy, had no extrarenal lupus manifestations at that time, and subsequently developed lupus nephritis (LN) or systemic lupus erythematosus (SLE) during the follow-up period at our center were included. Patients with sMN and incomplete SLE at the time of the initial renal biopsy were excluded from the study.ResultsA total of six patients were included. Of these, five were female and one was male. The mean age of the patients was 30.00 ± 10.39 years. At the initial renal biopsy, the proteinuria level was 6.45 ± 1.83 g/L, the serum albumin level was 21.77 ± 3.69 g/L, and the estimated glomerular filtration rate was within the normal range. Notably, one patient exhibited a positive test result for the PLA2R antibody, with a titer of 135.5 RU/ml. Following the administration of immunotherapy, all six patients achieved remission. However, after a follow-up period of 7.00 ± 5.21 years, five of the patients experienced a recurrence. Repeat renal biopsies in four relapsed patients confirmed histopathological progression to LN (class Ⅲ+Ⅴ in two cases, class V in two cases). Two patients subsequently fulfilled the 2019 EULAR/ACR SLE classification criteria.ConclusionThe diagnosis of membranous nephropathy does not entirely exclude the possibility of secondary nephropathy, even in patients with a high PLA2R antibody titer. Consequently, close longitudinal follow-up for occult autoimmune disease remains a necessity in clinical practice.

BackgroundHealthcare disparities in SLE randomized clinical trials (RCTs) are well known, with minoritized persons being under-represented as trial participants despite facing more significant SLE morbidity and mortality. There is currently limited information as to how to best recruit a diverse group of participants to SLE clinical trials. Barriers to clinical trial participation can originate from either the patients or their clinicians. We therefore sought to investigate the effectiveness of educational curriculum in decreasing such barriers.MethodsWe utilized materials from the American College of Rheumatology, the Lupus Research Alliance, and the Lupus Foundation to develop educational curriculums for both clinicians and patients to see if we could improve their knowledge, attitudes, and skills regarding clinical trial participation.ResultsAttitudes towards clinical trials were highly favorable among patients and clinicians prior to the workshop and remained positive afterwards. The workshops increased the patients' comfort level regarding clinical trial participation, and increased clinician comfort with the clinical trial process and how to refer patients to clinical trials. Regarding knowledge about clinical trials, the results were mixed, with certain knowledge aspects such as the protections afforded to patients in RCTs and SLE disparities improving, but knowledge about the more logistical and regulatory aspects of RCTs not significantly improving. However, these improvements did not translate into increasing patient enrollment into RCTs or research registries.ConclusionAlthough our study did increase both patients' and clinicians' skill and comfort level regarding RCT participation, its small size did not allow us to observe concrete gains in RCT enrollment.

BackgroundNeonatal lupus erythematosus (NLE) is a potentially life-threatening condition resulting from the transfer of autoantibodies from the mother to the fetus, with congenital heart block (CHB) its most serious complication. Despite the potential severity, therapeutic strategies remain limited. The objective was to systematically evaluate all registered clinical trials to date for the treatment or prevention of NLE and its cardiac manifestations.MethodsWe searched the Clinicaltrials.gov database on January 24, 2025, to identify all registered clinical trials for NLE treatments since 1994. This online registration of clinical trials is maintained by the NLM, a division of the National Institutes of Health (NIH), and mandates regular trial updates and timely results reporting. The registry provides specifics on a clinical trial, such as a national clinical trial (NCT) number, current recruitment status, study type, and other important data related to the trial. Principal investigators must submit results within 1 year of the trial's primary completion date.ResultsThree eligible trials for NLE were found on the NLM clinical trials database. One trial reported that hydroxychloroquine treatment reduced the recurrence rate of congenital heart block by more than half, from 18% to 7.4%. The remaining studies explored intravenous immunoglobulin and dexamethasone without posting results.ConclusionCongenital heart block from NLE was decreased in recurrence by treatment with hydroxychloroquine. However, the scarcity of research towards advancing care for these conditions highlights a major gap in this area.