Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 27 (10) ◽  
pp. 1644-1651 ◽  
Author(s):  
H H Kwon ◽  
S Y Bang ◽  
S Won ◽  
Y Park ◽  
J H Yi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Avascular Necrosis ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Individual Risk ◽  
High Dose ◽  
Systemic Lupus ◽  
Corticosteroid Dose ◽  
Increased Risk

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30–16.73), 0.58 (95% CI 0.36–0.81) and 2.66 (95% CI 1.42–4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

scholarly journals Efficacy of high-dose methylprednisolone and cyclophosphamide in childhood-onset systemic lupus erythematosus

2020 ◽  
Vol 60 (3) ◽  
pp. 116-23
Author(s):  
Putu Ayunda Trisnia ◽  
Ketut Dewi KUmara Wati ◽  
Komang Ayu Witarini ◽  
Ida Bagus Ramajaya Sutawan ◽  
Hendra Santoso
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
High Dose ◽  
Childhood Onset ◽  
Systemic Lupus ◽  
Sledai Score ◽  
Increased Risk ◽  
High Dose Methylprednisolone

Background Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease. Untreated SLE often become progressive and lead to increased risk of mortality. Corticosteroid and cyclophosphamide remain the treatment of choice for severe SLE. Disease activity assessed with SLE Daily Activity Index (SLEDAI). Objective To compare the disease activity of childhood-onset severe SLE at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide by using  SLEDAI. Methods This study was conducted in the Division of Pediatric Allergy and Immunology, Department of Child Health, Udayana University/Sanglah Hospital, Denpasar, Bali. Subjects were SLE patient aged 0-18 years who had severe clinical manifestations. Subject received therapy combination of high dose methylprednisolone and cyclophosphamide every 2 weeks for six doses. SLEDAI score was assessed at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide. Results During the study period, 51 children were diagnosed as SLE. Twenty-one subjects were included for analysis. Median SLEDAI score at the time of diagnosis was 23 (range 13-39). SLEDAI score after three months of cyclophosphamide was decreased to 2 (range 0-14). Post hoc analysis with Wilcoxon signed-rank test showed the improvement of SLEDAI score at the time of diagnosis and after three months of cyclophosphamide was statistically significant  (Z=-4.016, P<0.0001). Conclusion SLEDAI score reduced after completion of high-dose methylprednisolone and three month of cyclophosphamide therapy.

scholarly journals Efficacy of high-dose methylprednisolone and cyclophosphamide in childhood-onset systemic lupus erythematosus

2020 ◽  
Vol 60 (3) ◽  
pp. 117-24
Author(s):  
Putu Ayunda Trisnia ◽  
Ketut Dewi KUmara Wati ◽  
Komang Ayu Witarini ◽  
Ida Bagus Ramajaya Sutawan ◽  
Hendra Santoso
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
High Dose ◽  
Childhood Onset ◽  
Systemic Lupus ◽  
Sledai Score ◽  
Increased Risk ◽  
High Dose Methylprednisolone

Background Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease. Untreated SLE often become progressive and lead to increased risk of mortality. Corticosteroid and cyclophosphamide remain the treatment of choice for severe SLE. Disease activity assessed with SLE Daily Activity Index (SLEDAI). Objective To compare the disease activity of childhood-onset severe SLE at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide by using  SLEDAI. Methods This study was conducted in the Division of Pediatric Allergy and Immunology, Department of Child Health, Udayana University/Sanglah Hospital, Denpasar, Bali. Subjects were SLE patient aged 0-18 years who had severe clinical manifestations. Subject received therapy combination of high dose methylprednisolone and cyclophosphamide every 2 weeks for six doses. SLEDAI score was assessed at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide. Results During the study period, 51 children were diagnosed as SLE. Twenty-one subjects were included for analysis. Median SLEDAI score at the time of diagnosis was 23 (range 13-39). SLEDAI score after three months of cyclophosphamide was decreased to 2 (range 0-14). Post hoc analysis with Wilcoxon signed-rank test showed the improvement of SLEDAI score at the time of diagnosis and after three months of cyclophosphamide was statistically significant  (Z=-4.016, P<0.0001). Conclusion SLEDAI score reduced after completion of high-dose methylprednisolone and three month of cyclophosphamide therapy.

Missed hypereosinophilic syndrome in a critically ill patient with systemic lupus erythematosus

2021 ◽  
Vol 14 (1) ◽  
pp. e236592
Author(s):  
Ying Ling ◽  
Mary Jane Bell ◽  
Lisa Chodirker ◽  
Shirley Lake
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Hypereosinophilic Syndrome ◽  
Clinical Manifestations ◽  
Critically Ill Patient ◽  
Total Leucocyte Count ◽  
High Dose ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Systemic Lupus

A high functioning 74-year-old man with systemic lupus erythematosus presented to the emergency department with acute anxiety. He was found to have elevated cardiac enzymes and admitted to the cardiology service for investigation. In hospital, he developed an erythematous papular rash, and deteriorated to being somnolent and bedridden. He was found to have new multiterritory ischaemic strokes. It was eventually noted that he had persistent eosinophilia, present even on admission, which had been overlooked as the total leucocyte count was normal. Serology for antiphospholipid antibody syndrome (APS) was positive. He was diagnosed with hypereosinophilic syndrome (HES) secondary to new APS, and responded to high-dose steroids. This case highlights the importance of fully evaluating a leucocyte differential to make a diagnosis of HES. We discuss the definition, clinical manifestations, diagnostic approach and management of this important condition.

scholarly journals P0897RISK FACTORS FOR AVASCULAR BONE NECROSIS IN PATIENTS WITH LUPUS NEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Daniela Monova ◽  
Simeon Monov ◽  
Assen Kamenov ◽  
Vladislava Milenova
Keyword(s):  
Risk Factors ◽  
Lupus Nephritis ◽  
Avascular Necrosis ◽  
Immunosuppressive Agents ◽  
Individual Risk ◽  
Control Group ◽  
High Dose ◽  
Increased Risk ◽  
Avascular Necrosis Of Bone ◽  
Class Iv

Abstract Background and Aims Avascular necrosis of bone (AVN) is an important complication of systemic lupus erythematosus (SLE) and often causes serious physical disability. The aim of this study was to investigate the risk factors for symptomatic avascular necrosis of bone (AVN) in lupus nephritis (LN) patients. Method The records of 374 patients (43 males, 331 females) with kidney biopsy-proven LN were reviewed retrospectively. Symptomatic AVN cases were defined as those with at least one diagnosis of AVN. The patients with LN who did not have AVN were evaluated as a control group. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Results Symptomatic AVN was present in 17 patients (4 males, 13 females, mean age of 27,4±6,7 years). Among the 17 patients, 28 joints presented AVN. 12 occurred in hips (2 bilateral), 6-in ankles, 4-in knees, 3-in shoulders and 1- in lumbar spine. In 9 patients AVN involved 2 or more joints. 14 patients were on steroids at the time of presentation of AVN. 2 patients were not on CS and 1 patient did not has documentation of steroid use. Meta-analysis demonstrates a significant increased risk of AVN in patients with high disease activity and class IV LN (p&lt;0,005). LN patients with AVN showed an earlier onset age (p&lt;0,05) and received significantly higher total cumulative corticosteroid dose. AVN was not significantly associated with use of immunosuppressive agents. Serositis, coagulation disorders, vasculitis, cigarette smoking were higher incidence in male with LN and AVN. Raynaud‘s phenomenon, autoimmune thyroiditis, arthritis, Sjögren’s syndrome, IgM anticardiolipin antibodies, antiphospholipid syndrome, Cushingoid body habitus were higher incidence in female with LN and AVN. Conclusion Many risk factors have been involved in the development of AVN in LN patients. AVN is prevalent in class IV LN and in younger patients. Since asymptomatic osteonecrosis may remain undetected, its true prevalence could be much higher than we reported. Multifocal lesions involving more than three anatomical sites are unusual. Corticosteroids are the principal risk factor, although some cases of AVN occur in relatively steroid naïve patients. Early detection of AVN is important because the prognosis depends of the stage and location of the lesion. An individual risk assessment for AVN development should be made prior to and during treatment for LN, especially in patients high dose corticosteroids.

The Potential Role of Interferon-regulatory Factor 7 Among Taiwanese Patients with Systemic Lupus Erythematosus

2011 ◽  
Vol 38 (9) ◽  
pp. 1914-1919 ◽  
Author(s):  
LI-HSIN LIN ◽  
PIN LING ◽  
MING-FEI LIU
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Control Group ◽  
Type I ◽  
Mrna Levels ◽  
Regulatory Factor ◽  
Systemic Lupus ◽  
Increased Risk

Objective.Type I interferons (IFN), especially IFN-α, have been proposed to underlie the pathogenesis of systemic lupus erythematosus (SLE). Members of the IFN regulatory factor (IRF) family, which regulate IFN expression, have been implicated as risk factors for SLE. Our aims were to investigate the expression of IRF7 and its correlation with disease activity and to explore the association in Taiwanese patients between 2 genetic single-nucleotide polymorphisms (SNP) of IRF7 and SLE.Methods.IRF7 messenger RNA (mRNA) levels were measured in peripheral blood mononuclear cells by real-time reverse transcription polymerase chain reaction in 51 adult patients with SLE and 65 age-matched and sex-matched controls. Their serum IFN-α levels were determined by ELISA and the clinical manifestations were recorded at the same time. Two IRF7 SNP, rs1061501 and rs1061502, were examined by genotyping across 92 patients with SLE and 92 age and sex-matched healthy control subjects.Results.Compared with controls, the expression of IRF7 mRNA was significantly increased in patients with SLE and was positively correlated with both the serum level of IFN-α and lupus disease activity. The distribution of SNP rs1061501 by genotype (CC, CT, and TT) and by allele (C, T) was significantly different between the SLE and the control group (p = 0.028 for genotype and p = 0.009 for allele). There were no significant differences for SNP rs1061502.Conclusion.The results suggest that dysregulation of IRF7 might mediate an excessive production of IFN-α, which then exerts a crucial effect on the pathogenesis of human SLE. The IRF7 SNP rs1061501 TT genotype and T allele are enriched in Taiwanese patients with SLE and thus would seem to be associated with an increased risk of developing SLE.

Non-corticosteroid risk factors of symptomatic avascular necrosis of bone in systemic lupus erythematosus: A retrospective case-control study

2014 ◽  
Vol 25 (4) ◽  
pp. 590-594 ◽  
Author(s):  
Seyedeh Tahereh Faezi ◽  
Azam Sadat Hoseinian ◽  
Pedram Paragomi ◽  
Mahmood Akbarian ◽  
Fatemeh Esfahanian ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Avascular Necrosis ◽  
Lupus Erythematosus ◽  
Case Control Study ◽  
Case Control ◽  
Systemic Lupus ◽  
Retrospective Case ◽  
Avascular Necrosis Of Bone ◽  
Control Study

Thrombosis in Systemic Lupus Erythematosus and Other Autoimmune Diseases of Recent Onset

2009 ◽  
Vol 36 (1) ◽  
pp. 68-75 ◽  
Author(s):  
JUANITA ROMERO-DÍAZ ◽  
ICELLINI GARCÍA-SOSA ◽  
JORGE SÁNCHEZ-GUERRERO
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Venous Insufficiency ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Total Study Population ◽  
Recent Onset ◽  
Increased Risk

ObjectiveTo determine the risk of thrombosis in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases of recent onset.MethodsA retrospective cohort of 482 patients, mean age 28.3 years, with SLE or other autoimmune diseases was analyzed. Followup started at diagnosis or first appointment within 12 months since diagnosis until the development of thrombosis, end of study, loss to followup, or death. Thromboses were diagnosed upon clinical manifestations and confirmed by appropriate studies. Clinical variables were retrieved from the medical records, and SLE activity was assessed from the medical notes at onset of thrombosis, or at a dummy date for thrombosis, using the SLE Disease Activity Index-2K.ResultsDuring 2936 patient-years of followup, thromboses occurred in 49 patients (20.3%) with SLE and 6 patients (2.5%) with other autoimmune diseases. The incidence rate of thrombosis was 36.3 and 3.8 per 1000 patient-years in SLE and in other autoimmune diseases, respectively; relative risk 9.6 (95% CI 4.1–27.4, p < 0.0001). Throughout the disease course, the risk of thrombosis remained high in the SLE group, while in patients with other autoimmune diseases this risk was lower. The incidence of venous and arterial thrombosis was similar among SLE patients and patients with other autoimmune diseases. SLE and venous insufficiency were associated with thromboses in the total study population, and with venous insufficiency, vasculitis, and disease activity in the SLE group.ConclusionPatients with autoimmune diseases, particularly SLE, are at an increased risk of thrombosis. In patients with SLE, the risk remains elevated throughout the course of the disease.

Osteoporosis in a murine model of postmenopausal lupus

Lupus ◽  
2019 ◽  
Vol 29 (1) ◽  
pp. 58-66
Author(s):  
J Nordqvist ◽  
M K Lagerquist ◽  
L Grahnemo ◽  
A Koskela ◽  
U Islander ◽  
...  
Keyword(s):  
Risk Factors ◽  
Computed Tomography ◽  
Systemic Lupus Erythematosus ◽  
Experimental Model ◽  
Lupus Erythematosus ◽  
Mineral Density ◽  
Systemic Lupus ◽  
New Therapies ◽  
Increased Risk ◽  
Bone Remodeling Markers

Background/objective Postmenopausal women with systemic lupus erythematosus have an increased risk of osteoporosis and associated fractures. Their increased osteoporosis risk is probably caused by a high level of inflammation, use of glucocorticoids, impaired kidney function, and early menopause as these are known risk factors for osteoporosis. Due to these risk factors and the lack of safe and effective treatments, new therapies for the treatment of osteoporosis in this group of patients are needed. Ovariectomized MRL/ lpr mice constitute a well-established model for studies of postmenopausal systemic lupus erythematosus; however, it is not clear to what extent this experimental model is associated with the development of osteoporosis. Thus, the aim of this study was to characterize the skeleton of ovariectomized MRL/ lpr mice to determine the suitability of this model in studies of prospective new therapies for osteoporosis in postmenopausal systemic lupus erythematosus patients. Methods Skeletal parameters were measured in MRL/ lpr mice and MRL/++ control mice, using peripheral quantitative computed tomography, high-resolution micro-computed tomography and biomechanical analyses. mRNA expression of bone-remodeling markers was measured by quantitative polymerase chain reaction and serological markers of lupus disease were evaluated using ELISA. Results Total bone mineral density was reduced in MRL/ lpr mice compared with MRL/++ mice and MRL/ lpr mice had reduced cortical and trabecular bone thickness compared with MRL/++ mice. In line with the low bone mass of MRL/ lpr mice, gene expression analysis of cortical bone from these mice indicated an increased osteoclast activity as well as a decreased osteoblastogenesis and osteoblast activity, compared with MRL/++ mice. Conclusion Ovariectomized MRL/ lpr mice constitute a valuable experimental model for studies of osteoporosis development in postmenopausal systemic lupus erythematosus and this model is thus suitable for future studies of osteoporosis treatment in systemic lupus erythematosus.

Cardiovascular Disease in Systemic Lupus Erythematosus: Recent Data on Epidemiology, Risk Factors and Prevention

2020 ◽  
Vol 18 (6) ◽  
pp. 549-565 ◽  
Author(s):  
Myrto Kostopoulou ◽  
Dionysis Nikolopoulos ◽  
Ioannis Parodis ◽  
George Bertsias
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Statin Treatment ◽  
Type I Interferons ◽  
Type I ◽  
Lifestyle Modifications ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Atherogenic Dyslipidaemia

Systemic Lupus Erythematosus (SLE) is associated with increased risk for accelerated atherosclerosis and cardiovascular (CV) events including coronary heart disease, cerebrovascular and peripheral artery disease. CV events occur both early and late during the disease course, with younger patients being at much higher risk than age-matched counterparts. The risk cannot be fully accounted for by the increased prevalence of traditional atherosclerotic factors and may be due to pathophysiologic intermediates such as type I interferons and other inflammatory cytokines, oxidative stress, activated granulocytes and production of extracellular chromatin traps, antiphospholipid and other autoantibodies causing dysfunction of lipoproteins, altogether resulting in endothelial injury and pro-atherogenic dyslipidaemia. These mechanisms may be further aggravated by chronic intake of prednisone (even at doses <7.5 mg/day), whereas immunomodulatory drugs, especially hydroxychloroquine, may exert antiatherogenic properties. To date, there is a paucity of randomized studies regarding the effectiveness of preventative strategies and pharmacological interventions specifically in patients with SLE. Nevertheless, both the European League Against Rheumatism recommendations and extrapolated evidence from the general population emphasize that SLE patients should undergo regular monitoring for atherosclerotic risk factors and calculation of the 10-year CV risk. Risk stratification should include diseaserelated factors and accordingly, general (lifestyle modifications/smoking cessation, antihypertensive and statin treatment, low-dose aspirin in selected cases) and SLE-specific (control of disease activity, minimization of glucocorticoids, use of hydroxychloroquine) preventive measures be applied as appropriate. Further studies will be required regarding the use of non-invasive tools and biomarkers for CV assessment and of risk-lowering strategies tailored to SLE.

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