scholarly journals THU0515 SYSTEMIC LUPUS ERYTHEMATOSUS IN CHILDHOOD AND ADOLESCENCE - UPDATE FROM THE NATIONAL PEDIATRIC RHEUMATOLOGY DATABASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 496.2-496
Author(s):  
C. Sengler ◽  
M. Niewerth ◽  
N. Geisemeyer ◽  
H. Girschick ◽  
A. Klein ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mycophenolate Mofetil ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Pediatric Rheumatology ◽  
Kidney Biopsy ◽  
Organ Involvement ◽  
Childhood And Adolescence ◽  
Systemic Lupus ◽  
Kidney Involvement

Background:Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which begins in childhood and adolescence in 15 - 20% of cases. Since 2004, data on SLE have been collected by means of a disease-specific questionnaire as part of the National pediatric rheumatology database (NPRD) in Germany. Since 2014, kidney biopsy results have been recorded to further specify kidney involvement.Objectives:Evaluation of clinical signs and symptoms, outcome and laboratory data of patients with juvenile systemic lupus erythematosus from a large database in Germany.Methods:Data from patients with SLE recorded in the NPRD in 2017 were considered for the analysis. In addition to age, sex, onset of disease, the criteria that led to the diagnosis, various laboratory parameters, organ involvement (current, ever) and therapy (current, last 12 months), current disease activity (numerical rating scale 0-10, NRS) and ECLAM (score 0-10) were recorded. Patient-reported outcomes included global assessments of overall-wellbeing and fatigue (NRS 0-10) and functional ability (CHAQ).Results:196 patients (86% female) with a median age of 16 years were documented. Criteria most frequently met at diagnosis included “antinuclear antibodies” (88%), followed by “anti-ds-DNA-Ab” (66%), “butterfly erythema” (42%) and “arthritis” (41%). A positive family history was found in 10% of patients.At documentation, 85% of patients received disease-modifying anti-rheumatic drugs, most frequently hydroxychloroquine (73%), followed by mycophenolate mofetil (32%) and azathioprine (17%). Systemic glucocorticoids obtained 52% of patients, 12% ≥ 0.2 mg/kg/day. Biologics (rituximab 2%) and cyclophosphamide i.v. (3%) were rarely administered during the last 12 months. Disease activity was reported as 1.0 (NRS, median, IQR 0 - 9), ECLAM as 1.0 (median, range 0 - 10). In the laboratory, leukopenia < 3500/µl was found in 9% of patients, lymphopenia < 1500/µl in 47% and erythrocyte sedimentation rate (ESR) > 25 mm in 15% of patients. Mean CHAQ was 0.24, and 86% of patients had a CHAQ score < 0.5. Mean patient`s global assessment of overall-wellbeing was 1.5, while the mean fatigue score was 2.86 (18% NRS score 7-10).The following organ involvement was ever present: general symptoms 84%, skin/mucosa 72%, joints 73%, thyroid 15%, muscle 25%, lungs 17% and CNS 30%. In 45/190 (24%) patients, a kidney involvement was stated. In 34 patients (75%) a kidney biopsy was performed and histology yielded the following results: Class 1: 6.7%, Class 2: 16.7%, Class 3: 40.0%, Class 4: 23.3%, Class 5: 13.3%.Conclusion:The most common clinical symptoms documented in juvenile SLE patients were skin and joint involvement. In the course of the disease, a quarter of the patients developed kidney involvement, mostly proliferative nephritis. Apparently, azathioprine is increasingly being replaced by mycophenolate mofetil, biologicals have hardly been used so far. Although functional outcome and overall-wellbeing of jSLE patients was good, fatigue was a concern for some patients.Disclosure of Interests:Claudia Sengler: None declared, Martina Niewerth: None declared, Nils Geisemeyer: None declared, Hermann Girschick: None declared, Ariane Klein Consultant of: Celgene, Annette Friederike Jansson: None declared, Markus Hufnagel: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche

scholarly journals POS0685 MYCOPHENOLATE MOFETIL IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: FIVE-YEARS DRUG SURVIVAL IN RENAL AND NON-RENAL INVOLVEMENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 588.2-588
Author(s):  
G. Olivieri ◽  
F. Ceccarelli ◽  
F. Natalucci ◽  
F. R. Spinelli ◽  
C. Alessandri ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mycophenolate Mofetil ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Treatment Duration ◽  
Retention Rate ◽  
Renal Involvement ◽  
Joint Involvement ◽  
Systemic Lupus ◽  
Median Treatment

Background:The updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) underline the use of Mycophenolate Mofetil (MMF) in the treatment of different disease related manifestations (1). Several randomized controlled trials have demonstrated the efficacy of MMF in lupus nephritis (LN) patients but only case series and open-labelled trials have analyzed the use of this drug in other than LN features. Moreover, no data are available about the MMF retention rate in a real-life setting.Objectives:The present study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a large monocentric SLE cohort. Secondly, we investigated the influence of MMF in disease activity changes and chronic damage progression.Methods:We performed a longitudinal study including all the SLE patients (ACR 1997 criteria) starting MMF treatment in our Lupus Clinic. Data about indications, mean dosage, duration of treatment and reasons for drug withdrawal were registered. The DRR was estimated using the Kaplan–Meier method. Disease activity and chronic damage were assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SLICC Damage Index (SDI), respectively.Results:The present analysis included 162 SLE patients (M/F 22/140, median age at the disease diagnosis 25.5 years, IQR 13). At the beginning of MMF treatment, we registered a median age of 34 months (IQR 21) and a median disease duration of 72 months (IQR 123). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%), followed by neuropsychiatric involvement (10, 6.2%), and others disease related manifestations (12, 7.4%; in particular skin involvement, hematological features, myositis, vasculitis). MMF was administered at a mean daily dosage of 2.1±0.6 grams; no differences in dosage were found between the different indications (p=ns).At the longitudinal analysis, we registered a median treatment duration of 30 months (IQR 55). Figure 1 reported data about DRR: in particular, at 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (NLN) (60.5%; p=ns). Interestingly, the DRR at 60 months was higher in the subgroup of patients treated for joint involvement (75.4%), even without reaching a statistically significant difference. During the observation period, 92 patients (59.2%) discontinued MMF (median treatment duration at discontinuation 25 months, IQR 35). Interestingly, the main cause of withdrawal was the achievement of persistent remission, observed in 20 patients (21.7%), followed by loss of efficacy (19 patients, 20.5%), drug intolerance and pregnancy planning (17 patients for both reasons, 18,4%). Furthermore, our analysis confirmed MMF efficacy, as demonstrated by the significant reduction in SLEDAI-2k values after 4, 12 and 24 months of treatment (p< 0.0001 for all the time-points in comparison with baseline). In addition, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last observation: 0.93, IQR 1; p=ns).Conclusion:The evaluation of a large SLE cohort demonstrated a good retention rate for MMF. In particular, our results demonstrated that MMF is also a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it is able to control disease activity and to prevent the progression of chronic damage.References:[1]Fanouriakis A et al. Ann Rheum Dis. 2019 Jun;78(6):736-745.Disclosure of Interests:None declared

Structural and Neurochemical Markers of Brain Injury in the Migraine Diathesis of Systemic Lupus Erythematosus

Cephalalgia ◽  
1998 ◽  
Vol 18 (4) ◽  
pp. 209-215 ◽  
Author(s):  
CL Rozell ◽  
WL Sibbitt ◽  
WM Brooks
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Brain Injury ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Migraine Headache ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Recurrent Headache ◽  
Patients At Risk ◽  
Magnetic Resonance Imaging Mri

Objective: To determine whether migraine in systemic lupus erythematosus (SLE) is associated with accentuated brain injury and disease activity. Methods: Forty SLE patients (11 without headache, 11 with non-migraine headache, and 18 with migraine) underwent clinical evaluation, magnetic resonance imaging (MRI), and spectroscopy (MRS). Results: Recurrent headache occurred in 75% of SLE patients. MRI abnormalities and reduced N-acetylaspartate were common. However, migraine in SLE was not associated with increased disease activity or severity, neuropsychiatrie manifestations, or end-organ involvement compared to patients without migraine ( p>0.05). There were no differences in the prevalence or severity of MRI or MRS abnormalities between SLE patients with migraine, with non-migraine headache, or without headache ( p>0.05). Conclusions: Headache does not identify SLE patients at risk for brain injury, increased disease activity, or increased end-organ involvement. Aggressive immunosuppressive therapy for headache alone is not indicated in SLE.

scholarly journals A patient with systemic lupus erythematosus and lupus nephritis: A 12-year follow-up

2011 ◽  
Vol 68 (8) ◽  
pp. 705-708
Author(s):  
Natasa Jovanovic ◽  
Jasmina Markovic-Lipkovski ◽  
Stevan Pavlovic ◽  
Biljana Stojimirovic
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Nephrotic Syndrome ◽  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Biopsy ◽  
Immunosuppressive Drugs ◽  
Systemic Lupus ◽  
Younger Women ◽  
The Right

Introduction. Systemic lupus erythematosus (SLE) is a chronic immunological disease causing a significant morbidity and mortality in younger women and involving several organs and systems, most often the kidneys, being consequently the incidence of lupus nephritis (LN) about 60%. Case report. We reported a 57 year-old patient with the diagnosed SLE in 1995. Pathohistological analysis of kidney biopsy revealed LN type V. The patient was treated with corticosteroid pulses and azathioprine during one year. A remission was achieved and maintained with prednisone, 15 mg daily. Nephrotic relapse was diagnosed in 2006 and the second kidney biopsy revealed recent kidney infarction due to extensive vasculitis. Soon, a cerebrovascul insult developed and CT-scan revealed endocranial infarctus. The patient was treated with corticosteroids and cyclophosphamide pulses (totally VI monthly pulses), and also with low-molecular heparine, anticoagulants and salicylates because of the right leg phlebothrombosis. After the pulses, the patient was adviced to take prednisone 20 mg daily and azothioprine 100 mg daily, and 6 months later mycophenolate mofetil because of persistent active serological immunological findings (ANA 1 : 320) and nephrotic syndrome. Mycophenolate mofetil was efficient in inducing and maintaining remission of nephrotic syndrome. Conclusion. The aim of LN treatment is to achieve and maintain remission, improve patients? outcome, reduce the toxicity of immunosuppressive drugs and the incidence of relapses. Mycophenolate mofetil was shown to be efficient in inducing and maintaining remission of nephrotic syndrome in the frame of LN.

Increased CD4+CD25-Foxp3+ T cells in Chinese systemic lupus erythematosus: correlate with disease activity and organ involvement

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2057-2068 ◽  
Author(s):  
Z-J Yin ◽  
B-M Ju ◽  
L Zhu ◽  
N Hu ◽  
J Luo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cell Subset ◽  
Treg Cells ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Clinical Indicators ◽  
Disease States

Objective The increment of CD4+CD25−Foxp3+T cells has been reported in systemic lupus erythematosus (SLE) patients. However, the exact identity of this T cell subset is still unclear. Thus, we analyzed CD4+CD25−Foxp3+T cells and Treg cells (CD4+CD25+Foxp3+ T cells) in a large sample of Chinese SLE patients in different disease states. Methods A total of 280 SLE patients and 38 healthy volunteers were enrolled, which included 21 patients with untreated new-onset lupus (UNOL), 13 patients with drug withdrawal more than 6 months and 246 patients with treatments. Phenotypic and functional analysis of peripheral blood CD4+CD25−Foxp3+ T cells and Treg cells were performed by flow cytometry. The correlation of CD4+CD25−Foxp3+T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed. Results CD4+CD25−Foxp3+ T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4+CD25−Foxp3+ T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4+CD25−Foxp3+ T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4+CD25−Foxp3+ T cells expressed more IFN-γ and less CTLA-4 than CD4+CD25+Foxp3+ T cells, which were similar to CD4+CD25+Foxp3− T cells, and expressed similar IL-17, ICOS and Helios to CD4+CD25+Foxp3+ T cells. The synthesis capacity of IL-10 of CD4+CD25−Foxp3+ T cells and the expression of GITR on CD4+CD25−Foxp3+ T cells were between CD4+CD25+Foxp3+ and CD4+CD25+Foxp3− T cells. Conclusions Our results indicate that increased CD4+CD25−Foxp3+ T cells in lupus patients, which combined the features of suppression and pro-inflammatory, may serve as a biomarker for disease activity and organ involvement in SLE.

scholarly journals Extensive fragmentation and re-organization of gene co-expression patterns underlie the progression of Systemic Lupus Erythematosus

2020 ◽  
Author(s):  
Vasilis F. Ntasis ◽  
Nikolaos I. Panousis ◽  
Maria G. Tektonidou ◽  
Emmanouil T. Dermitzakis ◽  
Dimitrios T. Boumpas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Gene Expression Data ◽  
Lupus Erythematosus ◽  
Genome Organization ◽  
Expression Data ◽  
Systemic Lupus ◽  
Gene Coexpression ◽  
Kidney Involvement

AbstractSystemic Lupus Erythematosus (SLE) is the prototype of autoimmune diseases, characterized by extensive gene expression perturbations in peripheral blood immune cells. Circumstantial evidence suggests that these perturbations may be due to altered epigenetic profiles and chromatin accessibility but the relationship between transcriptional deregulation and genome organization remains largely unstudied. We developed a genomic approach that leverages patterns of gene coexpression from genome-wide transcriptome profiles in order to identify statistically robust Domains of Co-ordinated gene Expression (DCEs). By implementing this method on gene expression data from a large SLE patient cohort, we identify significant disease-associated alterations in gene co-regulation patterns, which also correlate with the SLE activity status. Low disease activity patient genomes are characterized by extensive fragmentation leading to DCEs of smaller size. High disease activity genomes display excessive spatial redistribution of co-expression domains with expanded and newly-appearing (emerged) DCEs. Fragmentation and redistribution of gene coexpression patterns correlate with SLE-implicated biological pathways and clinically relevant endophenotypes such as kidney involvement. Notably, genes lying at the boundaries of split DCEs of low activity genomes are enriched in the interferon and other SLE susceptibility signatures, suggesting the implication of DCE fragmentation at early disease stages. Interrogation of promoter-enhancer interactions from various immune cell subtypes shows that a significant percentage of nested connections are disrupted by a DCE split or depletion in SLE genomes. Collectively, our results underlining an important role for genome organization in shaping gene expression in SLE, could provide valuable insights into disease pathogenesis and the mechanisms underlying disease flares.SignificanceAlthough widespread gene expression changes have been reported in Systemic Lupus Erythematosus (SLE), attempts to link gene deregulation with genome structure have been lacking. Through a computational framework for the segmentation of gene expression data, we reveal extensive fragmentation and reorganization of gene co-regulation domains in SLE, that correlates with disease activity states. Gene co-expression domains pertaining to biological functions implicated in SLE such as the interferon pathway, are being disrupted in patients, while others associated to severe manifestations such as nephritis, emerge in previously uncorrelated regions of the genome. Our results support extensive genome re-organization underlying aberrant gene expression in SLE, which could assist in the early detection of disease flares in patients that are in remission.Graphical Abstract

scholarly journals Serum and Urinary Interleukin-6 in Assessment of Renal Activity in Egyptian Patients with Systemic Lupus Erythematosus

2016 ◽  
Vol 9 ◽  
pp. CMAMD.S32269 ◽  
Author(s):  
Rawhya R. EL-Shereef ◽  
Ahmed Lotfi ◽  
Emad A. Abdel-Naeam ◽  
Heba Tawfik
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Renal Biopsy ◽  
Lupus Erythematosus ◽  
Interleukin 6 ◽  
Control Group ◽  
Strong Positive Correlation ◽  
Systemic Lupus ◽  
Kidney Involvement ◽  
Significant Difference

Aim of the Work This study investigates whether serum and urinary interleukin-6 (IL-6) represent an early marker of kidney involvement and assesses the difference between them and renal biopsy in lupus nephritis (LN). Patients and Methods A total of 60 systemic lupus erythematosus (SLE) patients were compared to 20 healthy controls. Urinary and serum IL-6 were measured in both patients and controls. In addition, renal biopsy was done prior or shortly after urine and blood sampling; the results were classified according to the International Society of Nephrology/Renal Pathology Society classification of LN by recording the activity score and chronicity score for each sample. Results There was a significant higher level of urinary IL-6 in the SLE patients with biopsy-proven LN than in those without LN and those of the control group. However, no significant difference was reported between the three groups as regards serum IL-6. A strong positive correlation was found between urinary IL-6 and renal disease activity based on the renal SLE disease activity index (SLEDAI) score with no significant correlation regarding the extra renal SLEDAI. Urinary IL-6 was positively correlated with renal biopsy results and with its activity scores but weakly correlated with the chronicity scores. Conclusion Urinary IL-6 may provide a simple noninvasive potential marker of disease activity of renal involvement in adult patients with SLE.

Mycophenolate Mofetil in Nonrenal Manifestations of Systemic Lupus Erythematosus: An Observational Cohort Study

2016 ◽  
Vol 43 (3) ◽  
pp. 552-558 ◽  
Author(s):  
Konstantinos Tselios ◽  
Dafna D. Gladman ◽  
Jiandong Su ◽  
Murray B. Urowitz
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mycophenolate Mofetil ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Disease Duration ◽  
Activity Index ◽  
Standard Of Care ◽  
Systemic Lupus ◽  
Corticosteroid Dose ◽  
Extrarenal Manifestations

Objective.Mycophenolate mofetil (MMF), along with corticosteroids, is considered as the standard of care in lupus nephritis (LN); however, little is known regarding its efficacy in extrarenal manifestations of systemic lupus erythematosus (SLE). We aimed to determine its effectiveness in nonrenal SLE.Methods.One hundred seventy-seven patients with SLE were enrolled; 105 for whom MMF was introduced for active LN (mean age 35.6 ± 10.7 yrs, mean disease duration 8.9 ± 7.8 yrs) and 72 for extrarenal manifestations (mean age 38.6 ± 11.7 yrs, mean disease duration 11.7 ± 9.2 yrs). The main indication for MMF initiation was based on the respective SLE Disease Activity Index element that was present at that time. Patients were subdivided according to the major nonrenal manifestation. Improvement was defined as the absence of the initial clinical or laboratory manifestation after 6 and 12 months.Results.Cumulatively, the initial clinical manifestation or hematological abnormality was resolved in 42/72 nonrenal patients (58.3%) after 6 months and in 45/72 (62.5%) after 12 months. Corticosteroid dose was reduced in 44/72 patients (61.1%, p < 0.001, mean dose 18.4 ± 12.6 mg/day at baseline to 12.1 ± 9.0 mg/day after 12 mos, p < 0.05). In renal patients, 40 (38.1%) had complete resolution of the extrarenal manifestation after 6 months, while 53 (50.5%) achieved complete response after 12 months. Prednisone dose was reduced in 73/105 patients (69.5%) after 12 months (mean dose 29.2 ± 16.6 mg/day at baseline to 15.3 ± 9.7 mg/day, p < 0.001).Conclusion.MMF seems to be an efficacious alternative in refractory to standard of care nonrenal manifestations of SLE in the long term, allowing for disease activity control and significant reduction in corticosteroid dose.

Sign in / Sign up

Export Citation Format

Share Document