Risk of Serious Infection for Patients with Systemic Lupus Erythematosus Starting Glucocorticoids with or without Antimalarials

Objective.To compare serious infection risk for systemic lupus erythematosus (SLE) patients starting glucocorticoids (GC), antimalarials (AM), or their combination.Methods.We conducted a new-user, historical cohort study, Kaiser Permanente Northern California, 1997–2013. Cox proportional hazards analysis was used to calculate adjusted HR and 95% CI.Results.The study included 3030 patients with SLE followed an average of 4 years. Compared with patients starting AM without GC (9 infections/1461 patient-yrs), the HR for the risk of infection was 3.9 (95% CI 1.7–9.2) for those starting GC ≤ 15 mg/day without AM (14 infections/252 patient-yrs), while it was 0.0 (0 infections/128 patient-yrs) for those starting the combination. We split the 14 patients with a serious infection and with GC < 15 mg/day into 2 groups: < 7.5 and ≥ 7.5–15 mg/day. The HR for < 7.5 mg/day was 4.6 (95% CI 1.8–11.4) and for ≥ 7.5–15 mg/day, 3.1 (95% CI 1.0–9.7). For patients starting GC > 15 mg/day (reflecting more severe SLE), the risk of infection was nearly the same for the combination of GC and AM (9 infections/135 patient-yrs) and GC alone (41 infections/460 patient-yrs), but the combination users had evidence of more severe disease. Patients with SLE had a 6- to 7-fold greater risk of serious infection than the general population.Conclusion.Our findings suggest that the benefits of AM treatment for SLE may extend to preventing serious infections. Although the study included > 3000 patients, the statistical power to examine GC dosages < 15 mg/day was poor.

Download Full-text

Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women

Annals of the Rheumatic Diseases ◽

10.1136/ard.2007.072736 ◽

2007 ◽

Vol 67 (4) ◽

pp. 530-535 ◽

Cited By ~ 130

Author(s):

K H Costenbader ◽

D Feskanich ◽

M Holmes ◽

E W Karlson ◽

E Benito-Garcia

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Vitamin D ◽

Lupus Erythematosus ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Health Study ◽

Systemic Lupus ◽

Vitamin D Intake ◽

Incident Cases

Objectives:Vitamin D has immune-modulating effects and may protect against the development of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).Methods:We identified incident cases of SLE and RA among 186 389 women followed from 1980 to 2002 in the Nurses’ Health Study and Nurses’ Health Study II cohorts. We excluded subjects where SLE or RA was not confirmed by medical record review, and those who failed to return questionnaires. Semi-quantitative food frequency questionnaires assessed vitamin D intake from food and supplements. We used cumulative-updated total energy-adjusted dietary exposures for each 2-year cycle. Relationships between vitamin D intake and incident SLE and RA were examined in age-adjusted and Cox proportional hazards models, adjusted for confounders. Results were pooled using meta-analysis random effects models.Results:We confirmed 190 incident cases of SLE and 722 of RA with dietary information. Increasing levels of vitamin D intake had no relationship to the relative risk of developing either SLE or RA.Conclusions:Vitamin D intake was not associated with risk of SLE or RA in these large prospective cohorts of women.

Download Full-text

Risk factors for thrombotic events in Korean patients with systemic lupus erythematosus

Scientific Reports ◽

10.1038/s41598-021-03074-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dong-Jin Park ◽

Chang-Seok Yoon ◽

Sung-Eun Choi ◽

Haimuzi Xu ◽

Ji-Hyoun Kang ◽

...

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Protective Factor ◽

Proportional Hazards ◽

Damage Index ◽

Cox Proportional Hazards ◽

Systemic Lupus ◽

Vein Thrombosis ◽

Deep Vein

AbstractThrombotic events (TE), including deep vein thrombosis, stroke, and myocardial infarction, occur in 30–40% of patients with systemic lupus erythematosus (SLE) resulting in substantial morbidity and mortality. We explored the risk factors for TE in SLE patients. We analyzed data obtained during a prospective cohort based on the KORean lupus NETwork (KORNET) registry, and enrolled 259 SLE patients with clinical data available at the onset of SLE. TE was defined as the presence of arterial or venous thrombosis. Multivariate Cox-proportional hazards analysis was performed to investigate risk factors for TE. During a mean follow-up of 103.3 months (SD 53.4), 27 patients (10.4%) had a TE. In multivariate analysis, hypertension (hazard ratio [HR] 7.805, 95% confidence interval [CI]: 1.929–31.581; P = 0.004), anti-phospholipid syndrome (APS) (HR 12.600, 95% CI: 4.305–36.292; P < 0.001), mean daily prednisolone > 5 mg/day (HR 3.666, 95% CI: 1.318–10.197; P = 0.013), and SLICC/ACR Damage Index (SDI) score (HR 1.992, 95% CI: 1.465–2.709; P < 0.001) were significantly associated with the development of TE in SLE patients. Instead, use of an ACEi or ARB (HR 0.159, 95% CI: 0.043–0.594; P = 0.006) was a protective factor against TE development in these patients. In conclusion, hypertension, higher mean daily dose of prednisolone, diagnosis of APS, and higher SDI were risk factors for TE in patients with SLE. On the other hand, the use of an ACEi or ARB was associated with a reduced risk of TE.

Download Full-text

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.148502 ◽

2011 ◽

Vol 70 (10) ◽

pp. 1726-1732 ◽

Cited By ~ 91

Author(s):

J G Hanly ◽

M B Urowitz ◽

L Su ◽

S-C Bae ◽

C Gordon ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Systemic Lupus ◽

Case Definitions ◽

Total N ◽

Glycoprotein I ◽

Intracranial Thrombosis ◽

Ribosomal P

ObjectiveNeuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events.MethodsPatients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression.ResultsDisease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events.ConclusionIn a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

Download Full-text

New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond

Journal of Clinical Medicine ◽

10.3390/jcm9030712 ◽

2020 ◽

Vol 9 (3) ◽

pp. 712 ◽

Cited By ~ 4

Author(s):

Erkan Demirkaya ◽

Sezgin Sahin ◽

Micol Romano ◽

Qing Zhou ◽

Ivona Aksentijevich

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Current Knowledge ◽

Association Studies ◽

Severe Disease ◽

Genetic Diagnosis ◽

Genome Wide Association Studies ◽

Systemic Lupus ◽

Degree Relative ◽

Adult Age

Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (<5 years), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus but they inform considerable knowledge about cellular pathways contributing to this inflammatory phenotype. In recent years with the aid of new sequencing technologies, novel or rare pathogenic variants have been reported in over 30 genes predisposing to SLE and SLE-like diseases. Future studies will likely discover many more genes with private variants associated to lupus-like phenotypes. In addition, genome-wide association studies (GWAS) have identified a number of common alleles (SNPs), which increase the risk of developing lupus in adult age. Discovery of a possible shared immune pathway in SLE patients, either with rare or common variants, can provide important clues to better understand this complex disorder, it’s prognosis and can help guide new therapeutic approaches. The aim of this review is to summarize the current knowledge of the clinical presentation, genetic diagnosis and mechanisms of disease in patents with lupus and lupus-related phenotypes.

Download Full-text

Antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE) implies a more severe disease with more damage accrual and higher mortality

Lupus ◽

10.1177/0961203320950477 ◽

2020 ◽

Vol 29 (12) ◽

pp. 1556-1565

Author(s):

Leyre Riancho-Zarrabeitia ◽

Victor Martínez-Taboada ◽

Iñigo Rúa-Figueroa ◽

Fernando Alonso ◽

María Galindo-Izquierdo ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Severe Disease ◽

Organ Damage ◽

Systemic Lupus ◽

Katz Index ◽

Damage Accrual ◽

Major Organ ◽

Clinical Profiles

Introduction Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS). Materials and methods Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry. Results We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE ( p < 0.001). SLE-APS patients showed higher rates of neuropsychiatric, cardiac, pulmonary, renal and ophthalmological manifestations than the other groups ( p < 0.001). SLE-APS patients presented greater damage accrual with higher SLICC values (1.9 ± 2.2 in SLE-APS, 0.9 ± 1.4 in SLE-aPL and 1.1 ± 1.6 in SLE, p < 0.001) and more severe disease as defined by the Katz index (3 ± 1.8 in SLE-APS, 2.7 ± 1.7 in SLE-aPL and 2.6 ± 1.6 in SLE, p < 0.001). SLE-APS patients showed higher mortality rates ( p < 0.001). Conclusions SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.

Download Full-text

Transcriptome reprogramming and myeloid skewing in haematopoietic stem and progenitor cells in systemic lupus erythematosus

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2019-215782 ◽

2019 ◽

Vol 79 (2) ◽

pp. 242-253 ◽

Cited By ~ 6

Author(s):

Maria Grigoriou ◽

Aggelos Banos ◽

Anastasia Filia ◽

Pavlos Pavlidis ◽

Stavroula Giannouli ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Progenitor Cells ◽

Immune Cells ◽

Lupus Erythematosus ◽

Transcriptional Activation ◽

Severe Disease ◽

Enrichment Analysis ◽

Global Gene Expression ◽

Systemic Lupus ◽

Stem And Progenitor Cells

ObjectivesHaematopoietic stem and progenitor cells (HSPCs) are multipotent cells giving rise to both myeloid and lymphoid cell lineages. We reasoned that the aberrancies of immune cells in systemic lupus erythematosus (SLE) could be traced back to HSPCs.MethodsA global gene expression map of bone marrow (BM)-derived HSPCs was completed by RNA sequencing followed by pathway and enrichment analysis. The cell cycle status and apoptosis status of HSPCs were assessed by flow cytometry, while DNA damage was assessed via immunofluorescence.ResultsTranscriptomic analysis of Lin−Sca-1+c-Kit+ haematopoietic progenitors from diseased lupus mice demonstrated a strong myeloid signature with expanded frequencies of common myeloid progenitors (CMPs)—but not of common lymphoid progenitors—reminiscent of a ‘trained immunity’ signature. CMP profiling revealed an intense transcriptome reprogramming with suppression of granulocytic regulators indicative of a differentiation arrest with downregulation trend of major regulators such as Cebpe, Cebpd and Csf3r, and disturbed myelopoiesis. Despite the differentiation arrest, frequencies of BM neutrophils were markedly increased in diseased mice, suggesting an alternative granulopoiesis pathway. In patients with SLE with severe disease, haematopoietic progenitor cells (CD34+) demonstrated enhanced proliferation, cell differentiation and transcriptional activation of cytokines and chemokines that drive differentiation towards myelopoiesis, thus mirroring the murine data.ConclusionsAberrancies of immune cells in SLE can be traced back to the BM HSPCs. Priming of HSPCs and aberrant regulation of myelopoiesis may contribute to inflammation and risk of flare.Trial registration number4948/19-07-2016.

Download Full-text

Systemic lupus erythematosus and risk of infection

Expert Review of Clinical Immunology ◽

10.1080/1744666x.2020.1763793 ◽

2020 ◽

Vol 16 (5) ◽

pp. 527-538

Author(s):

Megan R.W. Barber ◽

Ann E. Clarke

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Risk Of Infection ◽

Systemic Lupus

Download Full-text

Serious infection incidence rates in pediatric systemic lupus erythematosus according to medication use

Arthritis Research & Therapy ◽

10.1186/ar4655 ◽

2014 ◽

Vol 16 (Suppl 1) ◽

pp. A39

Author(s):

Linda T Hiraki ◽

Candace H Feldman ◽

Mary Son ◽

Jessica M Franklin ◽

Michael A Fischer ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Medication Use ◽

Incidence Rates ◽

Systemic Lupus ◽

Pediatric Systemic Lupus Erythematosus ◽

Infection Incidence ◽

Serious Infection

Download Full-text

Childhood-onset bullous systemic lupus erythematosus

Lupus ◽

10.1177/0961203314544187 ◽

2014 ◽

Vol 23 (13) ◽

pp. 1422-1425 ◽

Cited By ~ 16

Author(s):

D M R Lourenço ◽

R Cunha Gomes ◽

N E Aikawa ◽

L M A Campos ◽

R Romiti ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Severe Disease ◽

Immunosuppressive Drugs ◽

University Hospital ◽

Direct Immunofluorescence ◽

Childhood Onset ◽

Systemic Lupus

Bullous systemic lupus erythematosus has rarely been described in pediatric lupus population and the real prevalence of childhood-onset bullous systemic lupus erythematosus has not been reported. From January 1983 to November 2013, 303 childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology Unit of the Childreńs Institute of Hospital das Clínicas da Faculdade de Medicina Universidade da Universidade de São Paulo, three of them (1%) diagnosed as childhood-onset bullous systemic lupus erythematosus. All three cases presented tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with the median duration of 60 days (30–60). All patients fulfilled bullous systemic lupus erythematosus criteria. Two had nephritis and serositis and presented specific autoantibodies. The histological pattern demonstrated subepidermal blisters with neutrophils-predominant infiltrates within the upper dermis. Direct immunofluorescence (DIF) showed deposits of IgG and complement along the epidermal basement membrane, in the presence or absence of IgA and/or IgM. A positive indirect immunofluorescence on salt-split skin demonstrating dermal binding was observed in two cases. All of them had moderate/severe disease activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 18 (14–24). Two patients received dapsone and one with severe nephritis received immunosuppressive drugs. In conclusion, in the last 30 years the prevalence of bullous lupus in childhood-onset lupus population was low (1%) in our tertiary University Hospital. A diagnosis of SLE should always be considered in children with recurrent tense vesiculobullous lesions with or without systemic manifestations.

Download Full-text