Retinal nerve fiber layer thickness and neuropsychiatric manifestations in systemic lupus erythematosus.

PubMed

Shulman, S; Shorer, R; Wollman, J; Dotan, G; Paran, D

2017-11-01

Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy controls. When evaluating by subgroups, no correlation was found between patients with or without neuropsychiatric systemic lupus erythematosus or cognitive impairment and retinal nerve fiber layer thickness. Conclusion Retinal nerve fiber layer thickness of systemic lupus erythematosus patients was not found to be statistically different compared to controls. Within systemic lupus erythematosus patients there was no correlation between retinal nerve fiber layer thickness and cognitive impairment or other neuropsychiatric systemic lupus erythematosus manifestations.

Outcomes of neuropsychiatric events in systemic lupus erythematosus based on clinical phenotypes; prospective data from the Leiden NP SLE cohort.

PubMed

Magro-Checa, C; Beaart-van de Voorde, L J J; Middelkoop, H A M; Dane, M L; van der Wee, N J; van Buchem, M A; Huizinga, T W J; Steup-Beekman, G M

2017-04-01

Objective The objective of this study was to assess whether clinical and patient's reported outcomes are associated with a different pathophysiological origin of neuropsychiatric events presenting in systemic lupus erythematosus. Methods A total of 232 neuropsychiatric events presenting in 131 systemic lupus erythematosus patients were included. Neuropsychiatric systemic lupus erythematosus diagnosis was established per event by multidisciplinary evaluation. All neuropsychiatric events were divided according to a suspected underlying pathophysiological process into one of the following: non-neuropsychiatric systemic lupus erythematosus related, inflammatory and ischaemic neuropsychiatric systemic lupus erythematosus. The clinical outcome of all neuropsychiatric events was determined by a physician-completed four-point Likert scale. Health-related quality of life was measured with the subscales of the patient-generated Short Form 36 (SF-36) health survey questionnaire. The change between scores at paired visits of all domain scores, mental component summary (SF-36 MCS) and physical component summary (SF-36 PCS) scores were retrospectively calculated and used as patient-reported outcome. The association among these outcomes and the different origin of neuropsychiatric events was obtained using multiple logistic regression analysis. Results The clinical status of 26.8% non-neuropsychiatric systemic lupus erythematosus events, 15.8% ischaemic neuropsychiatric systemic lupus erythematosus and 51.6% inflammatory neuropsychiatric systemic lupus erythematosus improved after re-assessment. Almost all SF-36 domains had a positive change at re-assessment in all groups independently of the origin of neuropsychiatric events. Neuropsychiatric systemic lupus erythematosus ( B = 0.502; p < 0.001) and especially inflammatory neuropsychiatric systemic lupus erythematosus ( B = 0.827; p < 0.001) had better clinical outcome, with change in disease activity being the only important predictor. The change in SF-36 MCS was also independently associated with neuropsychiatric systemic lupus erythematosus ( B = 5.783; p < 0.05) and inflammatory neuropsychiatric systemic lupus erythematosus ( B = 11.133; p < 0.001). Disease duration and change in disease activity were the only predictors in both cases. The change in SF-36 PCS was only negatively associated with age. Conclusion Inflammatory neuropsychiatric systemic lupus erythematosus events have better clinical outcome and meaningful improvement in SF-36 MCS than ischaemic neuropsychiatric systemic lupus erythematosus or non-neuropsychiatric systemic lupus erythematosus.

21 CFR 866.5820 - Systemic lupus erythema-tosus immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Systemic lupus erythema-tosus immunological test... Systems § 866.5820 Systemic lupus erythema-tosus immunological test system. (a) Identification. A systemic lupus erythematosus (SLE) immunological test system is a device that consists of the reagents used to...

Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study.

PubMed

Checa, A; Idborg, H; Zandian, A; Sar, D Garcia; Surowiec, I; Trygg, J; Svenungsson, E; Jakobsson, P-J; Nilsson, P; Gunnarsson, I; Wheelock, C E

2017-09-01

Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C 16:0 -ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C 16:0 -ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C 16:0 - and C 24:1 -hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

Lupus Anticoagulant-hypoprothrombinemia Syndrome (LAC-HPS) in Children With Systemic Lupus Erythematosus: Report of 3 Cases.

PubMed

Komvilaisak, Patcharee; Wisanuyotin, Suwannee; Jettrisuparb, Arunee; Wiangnon, Surapon

2017-11-01

Lupus anticoagulant, also known as lupus antibody, is generally associated with thrombosis rather than bleeding events. Lupus anticoagulant-hypoprothrombinemia syndrome in children is rather rare but can lead to mild to life-threatening bleeding. Here, we report 3 cases of lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus. They initially presented with mucocutaneous bleedings, and subsequently developed other symptoms fulfilling the laboratory criteria for systemic lupus erythematosus. Case 2 and 3 had significant epistaxis and intracerebral hemorrhage responded to systemic corticosteroid along with fresh frozen plasma. Three cases demonstrated acquired hypoprothrombinemia with no correction of mixing studies. Case 1 had low factor X level, which has never been reported previously. In all 3 cases, their coagulogram returned to normal level after corticosteroid treatment.

75 FR 35493 - Guidance for Industry on Systemic Lupus Erythematosus-Developing Medical Products for Treatment...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-22

...] (formerly Docket No. 2005D-0106) Guidance for Industry on Systemic Lupus Erythematosus--Developing Medical... entitled ``Systemic Lupus Erythematosus--Developing Medical Products for Treatment.'' This guidance... medical devices for the treatment of systemic lupus erythematosus (SLE). This guidance finalizes the draft...

Association between ulcerative colitis and systemic lupus erythematosus: report of two cases.

PubMed

Koutroubakis, I E; Kritikos, H; Mouzas, I A; Spanoudakis, S M; Kapsoritakis, A N; Petinaki, E; Kouroumalis, E A; Manousos, O N

1998-05-01

Common aetiopathogenic factors may explain the association of ulcerative colitis with autoimmune disorders such as systemic lupus erythematosus. We report two cases of ulcerative colitis associated with idiopathic systemic lupus erythematosus: one patient who developed ulcerative colitis 11 years after having been diagnosed as a case of systemic lupus erythematosus and one case of simultaneous appearance of the two diseases. The lupus clinical manifestations were in neither case correlated with the treatment of ulcerative colitis. The association between ulcerative colitis and systemic lupus erythematosus is rare. Although a chance occurrence cannot be excluded it is possible that both conditions share some genetic or immunological defects.

Risk factors for neuropsychiatric manifestations in children with systemic lupus erythematosus: case-control study.

PubMed

Zuniga Zambrano, Yenny Carolina; Guevara Ramos, Juan David; Penagos Vargas, Nathalia Elena; Benitez Ramirez, Diana Carol; Ramirez Rodriguez, Sandra Milena; Vargas Niño, Adriana Carolina; Izquierdo Bello, Alvaro Hernando

2014-09-01

Neuropsychiatric symptoms in children with systemic lupus erythematosus cause high morbidity and disability. This study analyzed risk factors associated with neuropsychiatric presentation in patients with systemic lupus erythematosus aged <18 years. A case-control study was performed. Medical record information of patients with a diagnosis of systemic lupus erythematosus who were hospitalized with or without neuropsychiatric symptoms was collected between March 2007 and January 2012. Clinical variables, laboratory examinations, neuroimages, and disease activity (Systemic Erythematosus Lupus Disease Activity Index) and damage (Systemic Lupus International Collaborating Clinics) indices were analyzed. A total of 90 patients were selected, 30 with neuropsychiatric symptoms. The patients' average age was 12.2 years. The most common neuropsychiatric symptoms were seizures, migraine, and depression. The average Systemic Erythematosus Lupus Disease Activity Index was 19.86 (S.D. 10.83) and the average Systemic Lupus International Collaborating Clinics index was 2.02 (S.D. 2.43), with higher values in patients with neuropsychiatric symptoms (P = 0.001). The levels of complement C3 and C4 were significantly higher in patients with a neuropsychiatric disorder (P = 0.003). Lupus anticoagulant was found in 51.5% of patients with neuropsychiatric symptoms (odds ratio, 3.7; 95% confidence interval, 1.3-10.0). Immunosuppression with azathioprine, rituximab, or cyclophosphamide delayed the time to neuropsychiatric systemic lupus erythematosus development by 18.5 months (95% confidence interval, 10.6-26.5) compared to patients who did not receive these agents. The presence of lupus anticoagulant was a risk factor in our patients. The use of immunosuppressants, such as cyclophosphamide, rituximab, and azathioprine, delayed the presentation of neuropsychiatric manifestations of lupus. Copyright © 2014 Elsevier Inc. All rights reserved.

Verrucous form of chilblain lupus erythematosus.

PubMed

Pock, L; Petrovská, P; Becvár, R; Mandys, V; Hercogová, J

2001-09-01

A 45-year-old woman had symmetrical livid plaques with yellowish hyperkeratoses for 5 years, which progressed on to the fingers and toes and on the soles of the feet. Two years later creamy, whitish areas and maceration appeared on the buccal mucosa and the lips. A skin biopsy revealed massive collagen hyaline degeneration in the perivascular area, hyperkeratosis and hypergranulosis, small lymphocyte infiltrates with several melanophages and extravasates of erythrocytes in the upper corium in perivascular areas and hydropic degeneration of basal keratinocytes. The findings using direct immunofluorescence were compatible with lupus erythematosus (LE). Laboratory investigation showed a slight leucopenia and thrombopenia, a slightly elevated erythrocyte sedimentation rate, hypocomplementaemia C3 and C4, a high titre of rheumatoid factor and antinuclear antibodies positivity of extractable nuclear antigen. The results reflected probably the development of a systemic form of the disease. The patient was successfully managed by methylprednisolone and hydroxychloroquine. After 1 year of therapy, a new skin biopsy revealed a substantial reduction of hyperkeratosis and hyaline degeneration of collagen tissue in the perivascular areas. The combination of the extensive hyperkeratosis and hyalinization thus seems to be features of the long-lasting, untreated lesions in chilblain LE.

The existential experience of everyday life with systemic lupus erythematosus.

PubMed

Larsen, Janni Lisander; Hall, Elisabeth O C; Jacobsen, Søren; Birkelund, Regner

2018-05-01

To explore from the perspective of women the nature of basic existential conditions while living with systemic lupus erythematosus. Systemic lupus erythematosus has an unpredictable disease course and is documented to cause an existential rearrangement of life. The significance of changes in existential conditions and related experiences are unclear in the context of nursing and women with systemic lupus erythematosus. A qualitative design guided by Van Manen's hermeneutic-phenomenological methodology. Individual in-depth interviews with 15 women diagnosed with systemic lupus erythematosus and of various ages, disease durations and severities were undertaken from September 2013 - October 2015. Data were analysed following van Manen's phenomenological approach and using drawing as an interpretive tool. The main existential experience was interpreted as a person "moving with the waves of systemic lupus erythematosus" constituted by the themes "oscillating between presence and absence of systemic lupus erythematosus," "recognizing space and bodily possibilities and limitations" and "being enriched through relationships and activities." When systemic lupus erythematosus was flaring, well-being was threatened and a laborious time to escape the feeling of a setback-in-life persisted long after the disease was medically under control. Daily life with systemic lupus erythematosus is conditioned by a prominent need to be in existential motion, related to the absence and presence of systemic lupus erythematosus. The experience of a setback-in-life by illness might challenge well-being and indicates that periods of disease flares or disturbing symptoms are critical time points to provide support. © 2018 John Wiley & Sons Ltd.

Risk of infective endocarditis in patients with systemic lupus erythematosus in Taiwan: a nationwide population-based study.

PubMed

Chang, Y S; Chang, C C; Chen, Y H; Chen, W S; Chen, J H

2017-10-01

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the control cohort. By contrast, the older systemic lupus erythematosus cohort had lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox multivariate proportional hazards analysis revealed heart disease (hazard ratio = 5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034), receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001), and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001) were independent risk factors for infective endocarditis in systemic lupus erythematosus patients. Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.

Lupus anticoagulants and antiphospholipid antibodies

MedlinePlus

Blood clots - lupus anticoagulants; DVT - anticoagulants ... Most often, lupus anticoagulants and aPL are found in people with diseases such as systemic lupus erythematosus (SLE). Lupus anticoagulants and ...

Gestational outcomes in patients with neuropsychiatric systemic lupus erythematosus.

PubMed

de Jesus, G R; Rodrigues, B C; Lacerda, M I; Dos Santos, F C; de Jesus, N R; Klumb, E M; Levy, R A

2017-04-01

This study analyzed maternal and fetal outcomes of pregnancies of neuropsychiatric systemic lupus erythematosus patients followed in a reference unit. This retrospective cohort study included 26 pregnancies of patients seen between 2011 and 2015 included with history and/or active neuropsychiatric systemic lupus erythematosus among 135 pregnancies. Three patients had active neuropsychiatric systemic lupus erythematosus at conception, but only one remained with neurological activity during gestation, characteristically related to the inadvertent suspension of medications. Twenty six percent of the newborns were small for gestational age and 40% of live births were premature, with no neonatal death or early complications of prematurity. Preeclampsia was diagnosed in nine pregnancies, with two cases of early severe form that resulted in intrauterine fetal death. Patients with neuropsychiatric systemic lupus erythematosus had more prematurity and preeclampsia compared to patients without neuropsychiatric disease. However, when concomitant lupus nephritis was excluded, the gestational results of neuropsychiatric systemic lupus erythematosus patients were more favorable.

Ki-67 proliferation index in renal biopsy samples of patients with systemic lupus erythematosus and its correlation with clinical findings.

PubMed

Dalkilic, Ediz; Filiz, Gulaydan; Yavuz, Mahmut; Dilek, Kamil; Ersoy, Alparslan; Yurtkuran, Mustafa; Oruc, Aysegul; Gul, Cuma Bulent; Gullulu, Mustafa

2013-05-01

Systemic lupus erythematosus is an autoimmune disease that may affect almost all organ systems. Renal involvement is the most significant prognostic factor. Renal biopsy findings play an important role in treatment decision. Ki-67 is a monoclonal antibody that is only found in proliferative cells. This study aimed to investigate the proliferative activity in renal biopsy specimens of patients with lupus nephritis using the Ki-67 monoclonal antibody, and to compare the proliferative index between different subgroups of patients. Renal biopsy specimens of 29 patients with systemic lupus erythematosus were retrospectively evaluated. Type of lupus nephritis and activity and chronicity indexes were determined. Ki-67 immunostaining was performed. For each patient, 1000 cells were counted and the number of Ki-67 positive cells was determined. The Ki-67 activity index was compared between different subgroups of lupus nephritis and correlated with systemic lupus erythematosus disease activity index, serum creatinine, proteinuria, anticardiolipin antibodies, and complement levels. A positive correlation between Ki-67 proliferation index, serum creatinine levels, and systemic lupus erythematosus disease activity index were found. Although conventional activity indexes were low, in 3 of 9 patients with class II lupus nephritis, Ki-67 proliferation indexes were high, indicating proliferation. Ki-67 can be used as a proliferation marker in renal biopsy specimens for patients diagnosed with systemic lupus erythematosus.

The role of epigenetic variation in the pathogenesis of systemic lupus erythematosus

PubMed Central

2011-01-01

The focus of the present review is on the extent to which epigenetic alterations influence the development of systemic lupus erythematosus. Lupus is a systemic autoimmune disease characterized by the production of autoantibodies directed at nuclear self-antigens. A DNA methylation defect in CD4+ T cells has long been observed in idiopathic and drug-induced lupus. Recent studies utilizing high-throughput technologies have further characterized the nature of the DNA methylation defect in lupus CD4+ T cells. Emerging evidence in the literature is revealing an increasingly interconnected network of epigenetic dysregulation in lupus. Recent reports describe variable expression of a number of regulatory microRNAs in lupus CD4+ T cells, some of which govern the expression of DNA methyltransferase 1. While studies to date have revealed a significant role for epigenetic defects in the pathogenesis of lupus, the causal nature of epigenetic variation in lupus remains elusive. Future longitudinal epigenetic studies in lupus are therefore needed. PMID:22044622

Health related quality of life in Mexican women with systemic lupus erythematosus: a descriptive study using SF-36 and LupusQoL(C).

PubMed

García-Carrasco, M; Mendoza-Pinto, C; Cardiel, M H; Méndez-Martínez, S; García-Villaseñor, A; Jiménez-Hernández, C; Alonso-García, N E; Briones-Rojas, R; Ramos-Álvarez, G; López-Colombo, A

2012-10-01

The LupusQoL© questionnaire is a disease-specific health related quality of life (HRQOL) instrument for adults with systemic lupus erythematosus (SLE). The Short Form-36 (SF-36) is a generic instrument that captures the physical, psychological, and social impact. We conducted a descriptive study of women aged ≥ 18 years attending our Lupus Clinic. HRQOL was assessed by applying the LupusQoL© and SF-36. Lupus activity was measured using the Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and chronic damage using the Systemic Lupus Collaborative Clinics Damage Index (SDI). Data were analyzed using descriptive statistics, the chi-square test and Pearson's product moment correlation coefficient. A total of 127 patients were included with a mean age of 40.5 ± 12.6 years. The mean disease duration was 8.2 ± 5.6 years, the mean disease activity score was 2.4 ± 3.0, and the mean SDI score 0.77 ± 1.06. The mean SF-36 score was 58.1 ± 21.1 and the mean LupusQoL© score was 69 ± 22.7. The correlation between global scores of the SF-36 and LupusQoL© was rho = 0.73 (p < 0.001). The correlation between lupus disease activity and the SF-36 and the LupusQoL© was -0.26 (p = 0.003) and -0.25 (p = 0.004), respectively. The correlation between the SDI and the SF-36 and the LupusQoL© was -0.28 (p = 0.001) and -0.38 (p < 0.0001), respectively. In conclusions: both LupusQoL© and SF-36 were useful instruments in assessing HRQOL in Mexican lupus female patients. The usefulness of the LupusQoL© should be evaluated in lupus patients with moderate to severe disease activity.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis.

PubMed

Hammad, A; Yahia, S; Laimon, W; Hamed, S M; Shouma, A; Shalaby, N M; Abdel-Hady, D; Ghanem, R; El-Farahaty, R M; El-Bassiony, S R; Hammad, E M

2017-06-01

Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( P<0.0001; odds ratio (OR) 2.4; 95% confidence interval (CI) 1.7-3.3) and the D allele was more frequent than the I allele in systemic lupus erythematosus patients in comparison to controls ( P < 0.0001; OR = 2.2; 95% CI = (1.6-3.1). In the lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P < 0.001; OR = 1.98; 95% CI = 1.3-2.9). Conclusion The D allele and DD genotype of the ACE gene appear to be a risk factor for the susceptibility of systemic lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

Hair and Scalp Changes in Cutaneous and Systemic Lupus Erythematosus.

PubMed

Udompanich, Siriorn; Chanprapaph, Kumutnart; Suchonwanit, Poonkiat

2018-06-09

Cutaneous and systemic lupus erythematosus (SLE) commonly involves the hair and scalp. Alopecia can result from direct activity of disease on the scalp or from the state of physical stress in the form of telogen effluvium. Discoid lupus erythematosus and lupus panniculitis/profundus are known to cause scarring alopecia, while accumulation of recent studies has shown that non-scarring alopecia in SLE may have different subtypes, comprising lupus erythematosus-specific and lupus erythematosus-nonspecific changes on histology. This review aims to summarize the clinical pattern, trichoscopic, histopathological, and direct immunofluorescence features of different types of alopecia in cutaneous and systemic lupus erythematosus, as well as exploring their relationship with SLE disease activity.

Pregnancy and contraception in systemic and cutaneous lupus erythematosus.

PubMed

Guettrot-Imbert, G; Morel, N; Le Guern, V; Plu-Bureau, G; Frances, C; Costedoat-Chalumeau, N

2016-10-01

A causal link has long been described between estrogen and systemic lupus erythematosus activity. Contraceptive and pregnancy management is now common for lupus patients, but pregnancy continues to be associated with higher maternal and fetal mortality/morbidity in systemic lupus erythematosus patients than among the general population. Potential complications include lupus flares, obstetric complications (fetal loss, in utero growth retardation, premature birth) and neonatal lupus syndrome. Association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetric complications. Anti-SSA and/or anti-SSB antibodies put fetuses at risk for neonatal lupus. Improving the outcome of such pregnancies depends upon optimal systematic planning of pregnancy at a preconception counseling visit coupled with a multidisciplinary approach. Absence of lupus activity, use of appropriate medication during pregnancy based on the patient's medical history and risk factors, and regular monitoring constitute the best tools for achieving a favorable outcome in such high-risk pregnancies. The aim of this review is to provide an update on the management of contraception and pregnancy in systemic lupus erythematosus, cutaneous lupus and/or antiphospholipid syndrome in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The systemic lupus erythematosus travel burden survey: baseline data among a South Carolina cohort.

PubMed

Williams, Edith M; Ortiz, Kasim; Zhang, Jiajia; Zhou, Jie; Kamen, Diane

2016-04-29

Many studies on the impact of systemic lupus erythematosus or lupus have identified patient travel costs as being problematic. We administered a survey that examined the impact of self-rated travel burden on lupus patients. The systemic lupus erythematosus travel burden survey included 41 patients enrolled in the systemic lupus erythematosus database project at the Medical University of South Carolina. Most participants reported that travel caused medications to be discontinued or appointments to be missed. In unadjusted logistic regressions of the relationship between these outcomes and medical travel burden, both distance to rheumatologists and time to lupus medical care were significant. Our findings suggest that more research is needed to examine the influence of travel burden among this population, but data from this report could help to inform physicians, academic researchers, and other health professionals in South Carolina and other areas with significant rural populations on how travel burden may impact patients receiving care for lupus and provide an opportunity for the development of interventions aimed at assisting lupus patients with management of stressors related to travel burden.

Novel Therapeutic Target for the Treatment of Lupus

DTIC Science & Technology

2013-12-01

RhoB. 15. SUBJECT TERMS RhoB, animal model, antibody secretion, antibody therapy, Systemic lupus erythematosus , autoantibodies. 16. SECURITY...9. Other Achievements 10. References 11. Appendices 1. INTRODUCTION: Systemic lupus erythematosus (SLE) affects approximately 300,000 to over...therapy, Systemic lupus erythematosus , autoantibodies. 3. OVERALL PROJECT SUMMARY: Objective to complete in the award period of 18 months

Discordant assessment of lupus activity between patients and their physicians: the Singapore experience.

PubMed

Leong, K P; Chong, E Y Y; Kong, K O; Chan, S P; Thong, B Y H; Lian, T Y; Chng, H H; Koh, E T; Teh, C L; Lau, T C; Law, W G; Cheng, Y K; Badsha, H; Chew, L C; Yong, W H; Howe, H S

2010-01-01

Patients with systemic lupus erythematosus often assess their disease activity differently from their physicians. We studied the factors associated with this discordance. The data provided by 534 systemic lupus erythematosus patients were analyzed. We compared the physician and patient assessments of lupus activity on a visual-assessment scale from the same visit. We collected clinical data and scores from MOS 36-Item Short-Form Health Survey, Systemic Lupus Erythematosus Quality-of-Life Questionnaire, Rheumatology Attitudes Index, Systemic Lupus Erythematosus Disease Activity Index, and revised Systemic Lupus Activity Measure. Patients tended to score their disease activity higher than do their physicians, when these factors were present: poorer general health assessment, presence of thrombocytopenia, hypertension and urinary sediments, and difficulty in carrying groceries. Physicians tended to score the disease activity higher than do the patients in these circumstances proteinuria, hemolysis, use of azathioprine or cyclophosphamide, tiredness, photosensitivity, higher revised Systemic Lupus Activity Measure score, casturia, and patient report of being more easily ill than are other patients. There was only moderate correlation between the discordance in the baseline and the subsequent visits. The physician assessment of disease activity at baseline correlated better with an objective measure of disease activity (revised Systemic Lupus Activity Measure) in the subsequent visit than the patient assessment. In conclusion, discordance in the perception of disease activity between patients and physicians may be amenable to intervention.

The lupus impact tracker is responsive to changes in clinical activity measured by the systemic lupus erythematosus responder index.

PubMed

Devilliers, H; Bonithon-Kopp, C; Jolly, M

2017-04-01

Objective The lupus impact tracker (LIT) is a 10-item patient reported outcome tool to measure the impact of systemic lupus erythematosus or its treatment on patients' daily lives. Herein, we describe the responsiveness of the LIT and LupusQoL to changes in disease activity, using the systemic lupus erythematosus responder index (SRI). Methods A total of 325 adult systemic lupus erythematosus patients were enrolled in an observational, longitudinal, multicentre study, conducted across the USA and Canada. Data (demographics, LIT, LupusQoL, BILAG, SELENA-SLEDAI) were obtained three months apart. Modified SRI was defined as: a decrease in SELENA-SLEDAI (4 points); no new BILAG A, and no greater than one new BILAG B; and no increase in the physician global assessment. Standardised response mean and effect size for LIT and LupusQoL domains were calculated among SRI responders and non-responders. Wilcoxon's test was used to compare the LIT and LupusQoL variation by SRI responder status. Results Of the participants 90% were women, 53% were white, 33% were of African descendant and 17% were Hispanic. Mean (SD) age and SELENA-SLEDAI at baseline were 42.3 (16.2) years and 4.3 (3.8), respectively. Mean (SD) LIT score at baseline was 39.4 (22.9). LIT standardised response mean (effect size) among SRI responders and non-responders were -0.69 (-0.36) and -0.20 (-0.12), respectively ( P = 0.02). For LupusQoL, two domains were responsive to SRI: standardised response mean (effect size) for physical health and pain domains were 0.42 (0.23) and 0.65 (0.44), respectively. Conclusions LIT is moderately responsive to SRI in patients with systemic lupus erythematosus. Inclusion of this tool in clinical care and clinical trials may provide further insights into its responsiveness. This is the first systemic lupus erythematosus patient reported outcome tool to be evaluated against composite responder index (SRI) used in clinical trials.

Aplastic anemia as a feature of systemic lupus erythematosus: a case report and literature review.

PubMed

Chalayer, Émilie; Ffrench, Martine; Cathébras, Pascal

2015-06-01

Peripheral cytopenias are common in systemic lupus erythematosus, but bone marrow involvement is rarely reported. Aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and characterized by an empty bone marrow. This rare but serious disease has been described as an unusual manifestation of systemic lupus erythematosus. We reviewed the 25 cases published in the English language literature and discuss the clinical presentation, outcome, treatment, and pathophysiology of aplastic anemia as a complication of systemic lupus erythematosus. We report here the first case of aplastic anemia associated with systemic lupus erythematosus treated with an allogeneic hematopoietic stem cell transplant. Over one half of patients received concomitantly the diagnoses of systemic lupus erythematosus and aplastic anemia. No clinical or histological features can distinguish primary aplastic anemia from aplastic anemia occurring in systemic lupus erythematosus patients. The overall mortality is about 15% and corticosteroid-based therapy alone or in combination with other immunomodulatory drugs can restore bone marrow function. Systemic lupus erythematosus may be complicated by bone marrow involvement. The diagnosis of peripheral cytopenias should be confirmed by bone marrow aspiration. All these patients should receive cortisone as a first treatment. Plasma exchanges seem to have some efficacy. Other different immunomodulatory therapies were used with variable results.

Atypical lupus erythematosus panniculitis progressing to antinuclear antibody-negative systemic lupus erythematosus.

PubMed

Pandhi, Deepika; Verma, Prashant; Singal, Archana; Sharma, Sonal; Tondon, Anupama

2012-01-01

Lupus erythematosus panniculitis (LEp) is an uncommon but distinctive subset of lupus erythematosus (LE). It may develop in patients with discoid or systemic LE or may occur as an isolated phenomenon. We describe a case of LEp affecting unusual sites: the parotid gland, eyelid, and scalp. Subsequently, the patient progressed to antinuclear antibody-negative systemic LE.

Hemophagocytic syndrome as one of the main primary manifestations in acute systemic lupus erythematosus--case report and literature review.

PubMed

Carvalheiras, G; Anjo, D; Mendonça, T; Vasconcelos, C; Farinha, F

2010-05-01

Hemophagocytic syndrome is an unusual but fatal disorder characterized by pancytopenia and activation of macrophages. We describe one case of acute systemic lupus erythematosus with an unusual presentation of hemophagocytic syndrome not related to infection. The patient presented with pancytopenia related to increasing hemophagocytic activity of histiocytes in the bone marrow. Concomitant class IV World Health Organization lupus nephritis, serositis, high titer of antinuclear factor and positive test for anti-DNA antibody fitted the diagnostic criteria of systemic lupus erythematosus. She also presented with alveolar hemorrhage and lupus myocarditis. She underwent immunosuppressive therapy with recovery from the hemophagocytic syndrome. Therefore, diagnosis of acute lupus hemophagocytic syndrome was made. The clinical presentation, laboratory diagnosis, and management of the patient are discussed and the literature was reviewed and presented, with emphasis on a possible distinct lupus subset, which includes a more aggressive systemic disease with heart involvement.

Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus.

PubMed

Mina, Rina; Abulaban, Khalid; Klein-Gitelman, Marisa S; Eberhard, Barbara A; Ardoin, Stacy P; Singer, Nora; Onel, Karen; Tucker, Lori; O'neil, Kathleen; Wright, Tracey; Brooks, Elizabeth; Rouster-Stevens, Kelly; Jung, Lawrence; Imundo, Lisa; Rovin, Brad; Witte, David; Ying, Jun; Brunner, Hermine I

2016-02-01

To validate clinical indices of lupus nephritis activity and damage when used in children against the criterion standard of kidney biopsy findings. In 83 children requiring kidney biopsy, the Systemic Lupus Erythematosus Disease Activity Index renal domain (SLEDAI-R), British Isles Lupus Assessment Group index renal domain (BILAG-R), Systemic Lupus International Collaborating Clinics (SLICC) renal activity score (SLICC-RAS), and SLICC Damage Index renal domain (SDI-R) were measured. Fixed effects and logistic models were calculated to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low-to-moderate versus high lupus nephritis activity (National Institutes of Health [NIH] activity index [AI]) score: ≤10 versus >10; tubulointerstitial activity index (TIAI) score: ≤5 versus >5; or the absence versus presence of lupus nephritis chronicity (NIH chronicity index) score: 0 versus ≥1. There were 10, 50, and 23 patients with ISN/RPS class I/II, III/IV, and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with lupus nephritis activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between lupus nephritis activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture lupus nephritis chronicity was 23.5% and 91.7%, respectively. Despite being designed to measure lupus nephritis activity, SLICC-RAS and SLEDAI-R scores significantly differed with lupus nephritis chronicity status. Current clinical indices of lupus nephritis fail to discriminate ISN/RPS class in children. Despite its shortcomings, the SLEDAI-R appears best for measuring lupus nephritis activity in a clinical setting. The SDI-R is a poor correlate of lupus nephritis chronicity. © 2016, American College of Rheumatology.

Tuberculosis and systemic lupus erythematosus: a case-control study in Mexico City.

PubMed

Torres-González, Pedro; Romero-Díaz, Juanita; Cervera-Hernández, Miguel Enrique; Ocampo-Torres, Mario; Chaires-Garza, Luis Gerardo; Lastiri-González, Ernesto Alejandro; Atisha-Fregoso, Yemil; Bobadilla-Del-Valle, Miriam; Ponce-de-León, Alfredo; Sifuentes-Osornio, José

2018-04-20

To determine, among systemic lupus erythematosus patients, factors associated with active tuberculosis. We performed a case-control study, in a tertiary-care center in Mexico City. We defined cases as systemic lupus erythematosus patients with active tuberculosis and matched them 1:1 with systemic lupus erythematosus patients without tuberculosis (controls) by age, date of systemic lupus erythematosus diagnosis, and disease duration. We analyzed clinical variables, lupus disease activity (SLEDAI-2K), and accumulated damage (SLICC/ARC-DI). We performed a nonconditional logistic regression to determine factors associated with tuberculosis. We identified 72 tuberculosis cases among systemic lupus erythematosus patients, 58% were culture confirmed. Thirty-three percent (24/72) were pulmonary only, 47.2% (34/72) extrapulmonary only, and 19.4% both. After adjustment for age, gender, and socioeconomic status, SLEDAI-2K and SLICC/ARC-DI, a 1-year cumulative dose of prednisone ≥ 3 g (odds ratios (OR), 18.85; 95% confidence interval (95% CI), 6.91-51.45) was associated with tuberculosis, and the antimalarial treatment was protective (OR, 0.13; 95% CI, 0.04-0.36). Among systemic lupus erythematosus patients, cumulative dose of prednisone is associated with tuberculosis. Further research is required to elucidate the protective effect of antimalarial drugs for tuberculosis. Preventive strategies must be implemented in patients at risk.

Clinical correlates and outcomes in a group of Puerto Ricans with systemic lupus erythematosus hospitalized due to severe infections

PubMed Central

Jordán-González, Patricia; Shum, Lee Ming; González-Sepúlveda, Lorena

2018-01-01

Objective: Infections are a major cause of morbidity and mortality in systemic lupus erythematosus. Clinical outcomes of systemic lupus erythematosus patients hospitalized due to infections vary among different ethnic populations. Thus, we determined the outcomes and associated factors in a group of Hispanics from Puerto Rico with systemic lupus erythematosus admitted due to severe infections. Methods: Records of systemic lupus erythematosus patients admitted to the Adult University Hospital, San Juan, Puerto Rico, from January 2006 to December 2014 were examined. Demographic parameters, lupus manifestations, comorbidities, pharmacologic treatments, inpatient complications, length of stay, readmissions, and mortality were determined. Patients with and without infections were compared using bivariate and multivariate analyses. Results: A total of 204 admissions corresponding to 129 systemic lupus erythematosus patients were studied. The mean (standard deviation) age was 34.7 (11.6) years; 90% were women. The main causes for admission were lupus flare (45.1%), infection (44.0%), and initial presentation of systemic lupus erythematosus (6.4%). The most common infections were complicated urinary tract infections (47.0%) and soft tissue infections (42.0%). In the multivariate analysis, patients admitted with infections were more likely to have diabetes mellitus (odds ratio: 4.20, 95% confidence interval: 1.23–14.41), exposure to aspirin prior to hospitalization (odds ratio: 4.04, 95% confidence interval: 1.03–15.80), and higher mortality (odds ratio: 6.00, 95% confidence interval: 1.01–35.68) than those without infection. Conclusion: In this population of systemic lupus erythematosus patients, 44% of hospitalizations were due to severe infections. Patients with infections were more likely to have diabetes mellitus and higher mortality. Preventive and control measures of infection could be crucial to improve survival in these patients.

Clinical correlates and outcomes in a group of Puerto Ricans with systemic lupus erythematosus hospitalized due to severe infections.

PubMed

Jordán-González, Patricia; Shum, Lee Ming; González-Sepúlveda, Lorena; Vilá, Luis M

2018-01-01

Infections are a major cause of morbidity and mortality in systemic lupus erythematosus. Clinical outcomes of systemic lupus erythematosus patients hospitalized due to infections vary among different ethnic populations. Thus, we determined the outcomes and associated factors in a group of Hispanics from Puerto Rico with systemic lupus erythematosus admitted due to severe infections. Records of systemic lupus erythematosus patients admitted to the Adult University Hospital, San Juan, Puerto Rico, from January 2006 to December 2014 were examined. Demographic parameters, lupus manifestations, comorbidities, pharmacologic treatments, inpatient complications, length of stay, readmissions, and mortality were determined. Patients with and without infections were compared using bivariate and multivariate analyses. A total of 204 admissions corresponding to 129 systemic lupus erythematosus patients were studied. The mean (standard deviation) age was 34.7 (11.6) years; 90% were women. The main causes for admission were lupus flare (45.1%), infection (44.0%), and initial presentation of systemic lupus erythematosus (6.4%). The most common infections were complicated urinary tract infections (47.0%) and soft tissue infections (42.0%). In the multivariate analysis, patients admitted with infections were more likely to have diabetes mellitus (odds ratio: 4.20, 95% confidence interval: 1.23-14.41), exposure to aspirin prior to hospitalization (odds ratio: 4.04, 95% confidence interval: 1.03-15.80), and higher mortality (odds ratio: 6.00, 95% confidence interval: 1.01-35.68) than those without infection. In this population of systemic lupus erythematosus patients, 44% of hospitalizations were due to severe infections. Patients with infections were more likely to have diabetes mellitus and higher mortality. Preventive and control measures of infection could be crucial to improve survival in these patients.

Lupus

MedlinePlus

... and brain. There are several kinds of lupus Systemic lupus erythematosus (SLE) is the most common type. ... medicine can treat lupus. Some alternative or complementary approaches may help you cope or reduce some of ...

Activation of Type I Interferon Pathway in Systemic Lupus Erythematosus: Association with Distinct Clinical Phenotypes

PubMed Central

Karageorgas, Theophanis P.; Tseronis, Dimitrios D.; Mavragani, Clio P.

2011-01-01

Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target. PMID:22162633

Heart rate variability in patients with systemic lupus erythematosus: a systematic review and methodological considerations.

PubMed

Matusik, P S; Matusik, P T; Stein, P K

2018-07-01

Aim The aim of this review was to summarize current knowledge about the scientific findings and potential clinical utility of heart rate variability measures in patients with systemic lupus erythematosus. Methods PubMed, Embase and Scopus databases were searched for the terms associated with systemic lupus erythematosus and heart rate variability, including controlled vocabulary, when appropriate. Articles published in English and available in full text were considered. Finally, 11 publications were selected, according to the systematic review protocol and were analyzed. Results In general, heart rate variability, measured in the time and frequency domains, was reported to be decreased in patients with systemic lupus erythematosus compared with controls. In some systemic lupus erythematosus studies, heart rate variability was found to correlate with inflammatory markers and albumin levels. A novel heart rate variability measure, heart rate turbulence onset, was shown to be increased, while heart rate turbulence slope was decreased in systemic lupus erythematosus patients. Reports of associations of changes in heart rate variability parameters with increasing systemic lupus erythematosus activity were inconsistent, showing decreasing heart rate variability or no relationship. However, the low/high frequency ratio was, in some studies, reported to increase with increasing disease activity or to be inversely correlated with albumin levels. Conclusions Patients with systemic lupus erythematosus have abnormal heart rate variability, which reflects cardiac autonomic dysfunction and may be related to inflammatory cytokines but not necessarily to disease activity. Thus measurement of heart rate variability could be a useful clinical tool for monitoring autonomic dysfunction in systemic lupus erythematosus, and may potentially provide prognostic information.

Alcohol, smoking and illicit drug use in pediatric systemic lupus erythematosus patients.

PubMed

van Weelden, Marlon; Queiroz, Lígia B; Lourenço, Daniela M R; Kozu, Katia; Lourenço, Benito; Silva, Clovis A

2016-01-01

To evaluate alcohol, smoking and/or illicit drug use, and history of bullying in adolescent childhood-onset systemic lupus erythematosus and healthy controls. 174 adolescents with pediatric rheumatic diseases were selected. All of the 34 childhood-onset systemic lupus erythematosus patients and 35 healthy controls participated in this study. A cross-sectional study included demographic/anthropometric data and puberty markers assessments; structured questionnaire and CRAFFT screening interview. McNemar tests indicated an excellent test-retest reliability of the structured questionnaire (p=1.0). The median current age was similar between childhood-onset systemic lupus erythematosus patients and controls [15 (12-18) vs. 15 (12-18) years, p=0.563]. The median of menarche age was significantly higher in childhood-onset systemic lupus erythematosus patients compared to controls [12 (10-15) vs. 11.5 (9-15) years, p=0.041], particularly in those that lupus had occurred before first menstruation [13 (12-15) vs. 11.5(9-15) years, p=0.007]. The other puberty marker and sexual function parameters were similar in both groups (p>0.05). Alcohol use was similar in both childhood-onset systemic lupus erythematosus patients and controls (38% vs. 46%, p=0.628). A trend of lower frequency of CRAFFT score ≥2 (high risk for substance abuse/dependence) was evidenced in childhood-onset systemic lupus erythematosus patients compared to controls (0% vs. 15%, p=0.053). Bullying was reported similarly for the two groups (43% vs. 44%, p=0.950). Further analysis in lupus patients regarding alcohol/smoking/illicit drug use showed no differences in demographic data, puberty markers, history of bullying, sexual function, contraceptive use, disease activity/damage scores, clinical/laboratorial features and treatments (p>0.05). This study showed high frequencies of early alcohol use in lupus adolescents and healthy controls, despite of a possible low risk for substance abuse/dependence in childhood-onset systemic lupus erythematosus patients. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Periorbital edema as initial manifestation of chronic cutaneous lupus erythematosus.

PubMed

Erras, Samar; Benjilali, Laila; Essaadouni, Lamiaa

2012-01-01

Periorbital edema occurs frequently in dermatomyositis, but it has rarely been noted in systemic systemic lupus erythematosus. We describe a patient who developed bilateral periorbital edema and erythema as the sole manifestation of systemic lupus erythematosus.

ABIN1 dysfunction as a genetic basis for lupus nephritis.

PubMed

Caster, Dawn J; Korte, Erik A; Nanda, Sambit K; McLeish, Kenneth R; Oliver, Rebecca K; G'sell, Rachel T; Sheehan, Ryan M; Freeman, Darrell W; Coventry, Susan C; Kelly, Jennifer A; Guthridge, Joel M; James, Judith A; Sivils, Kathy L; Alarcon-Riquelme, Marta E; Scofield, R Hal; Adrianto, Indra; Gaffney, Patrick M; Stevens, Anne M; Freedman, Barry I; Langefeld, Carl D; Tsao, Betty P; Pons-Estel, Bernardo A; Jacob, Chaim O; Kamen, Diane L; Gilkeson, Gary S; Brown, Elizabeth E; Alarcon, Graciela S; Edberg, Jeffrey C; Kimberly, Robert P; Martin, Javier; Merrill, Joan T; Harley, John B; Kaufman, Kenneth M; Reveille, John D; Anaya, Juan-Manuel; Criswell, Lindsey A; Vila, Luis M; Petri, Michelle; Ramsey-Goldman, Rosalind; Bae, Sang-Cheol; Boackle, Susan A; Vyse, Timothy J; Niewold, Timothy B; Cohen, Philip; Powell, David W

2013-11-01

The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-κB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-κB and mitogen-activated protein kinase activity.

ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

PubMed Central

Caster, Dawn J.; Korte, Erik A.; Nanda, Sambit K.; McLeish, Kenneth R.; Oliver, Rebecca K.; G'Sell, Rachel T.; Sheehan, Ryan M.; Freeman, Darrell W.; Coventry, Susan C.; Kelly, Jennifer A.; Guthridge, Joel M.; James, Judith A.; Sivils, Kathy L.; Alarcon-Riquelme, Marta E.; Scofield, R. Hal; Adrianto, Indra; Gaffney, Patrick M.; Stevens, Anne M.; Freedman, Barry I.; Langefeld, Carl D.; Tsao, Betty P.; Pons-Estel, Bernardo A.; Jacob, Chaim O.; Kamen, Diane L.; Gilkeson, Gary S.; Brown, Elizabeth E.; Alarcon, Graciela S.; Edberg, Jeffrey C.; Kimberly, Robert P.; Martin, Javier; Merrill, Joan T.; Harley, John B.; Kaufman, Kenneth M.; Reveille, John D.; Anaya, Juan-Manuel; Criswell, Lindsey A.; Vila, Luis M.; Petri, Michelle; Ramsey-Goldman, Rosalind; Bae, Sang-Cheol; Boackle, Susan A.; Vyse, Timothy J.; Niewold, Timothy B.; Cohen, Philip

2013-01-01

The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-κB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-κB and mitogen-activated protein kinase activity. PMID:23970121

The LupusQoL and associations with demographics and clinical measurements in patients with systemic lupus erythematosus.

PubMed

McElhone, Kathleen; Castelino, Madhura; Abbott, Janice; Bruce, Ian N; Ahmad, Yasmeen; Shelmerdine, Joanna; Peers, Kate; Isenberg, David; Ferenkeh-Koroma, Ada; Griffiths, Bridget; Akil, Mohammed; Maddison, Peter; Gordon, Caroline; Teh, Lee-Suan

2010-11-01

Having developed and validated a disease-specific health-related quality of life (HRQOL) measure for patients with systemic lupus erythematosus (SLE), the LupusQoL, we determined its relationship to demographic and clinical measurements in a group of patients with SLE. A group of 322 outpatients completed the LupusQoL. Demographic (age, sex, marital status, ethnicity) and clinical variables (disease duration, disease activity, damage) were recorded. Associations between the 8 LupusQoL domains and age, disease duration, disease activity, and damage were explored using Spearman's correlation coefficients. Differences in LupusQoL scores were examined for sex and marital status using the Mann-Whitney U test. Ethnic groups were compared using ANOVA. All domains of LupusQoL were impaired, with fatigue (56.3) being the worst affected and body image (80.0) the least. The correlations between the LupusQoL domain scores and age (r = -0.01 to -0.22) and disease duration (r = 0 to 0.16) were absent or weak. Similarly, there were no significant differences in the LupusQoL scores regarding sex, marital status, or the 3 main ethnic groups (Black-Caribbean, Asian, White). Although there were statistically significant correlations between the scores of the LupusQoL domains and some scores of the British Isles Lupus Assessment Group index (r = -0.22 to 0.09) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (r = -0.29 to 0.21), these were weak. HRQOL was impaired in this cohort of outpatients with SLE as assessed by the validated lupus-specific LupusQoL. There were no clinically important associations between the 8 domains of the LupusQoL and clinical or demographic variables in this group of patients. Thus, the LupusQoL is a relatively independent outcome measure in patients with SLE.

Childhood-onset bullous systemic lupus erythematosus.

PubMed

Lourenço, D M R; Gomes, R Cunha; Aikawa, N E; Campos, L M A; Romiti, R; Silva, C A

2014-11-01

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. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Lupus erythematosus: considerations about clinical, cutaneous and therapeutic aspects*

PubMed Central

Moura Filho, Jucélio Pereira; Peixoto, Raiza Luna; Martins, Lívia Gomes; de Melo, Sillas Duarte; de Carvalho, Ligiana Leite; Pereira, Ana Karine F. da Trindade C.; Freire, Eutilia Andrade Medeiros

2014-01-01

Systemic Lupus Erythematosus is a chronic inflammatory disease with multifactorial etiology. Although clinical manifestations are varied, the skin is an important target-organ, which contributes to the inclusion of skin lesions in 4 out of the 17 new criteria for the diagnosis of the disease, according to the Systemic Lupus International Collaborating Clinics. The cutaneous manifestations of lupus are pleomorphic. Depending on their clinical characteristics, they can be classified into Acute Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus and Intermittent Cutaneous Lupus Erythematosus. Treatment is based on preventive measures, reversal of inflammation, prevention of damage to target organs and relief of adverse events due to pharmacological therapy. The most commonly used treatment options are topical, systemic and surgical treatment, as well as phototherapy. The correct handling of the cases depends on a careful evaluation of the morphology of the lesions and the patient's general status, always taking into consideration not only the benefits but also the side effects of each therapeutic proposal. PMID:24626656

Periorbital edema as initial manifestation of chronic cutaneous lupus erythematosus

PubMed Central

Erras, Samar; Benjilali, Laila; Essaadouni, Lamiaa

2012-01-01

Periorbital edema occurs frequently in dermatomyositis, but it has rarely been noted in systemic systemic lupus erythematosus. We describe a patient who developed bilateral periorbital edema and erythema as the sole manifestation of systemic lupus erythematosus. PMID:22937197

Elevated sacroilac joint uptake ratios in systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Smet, A.A.; Mahmood, T.; Robinson, R.G.

1984-08-01

Sacroiliac joint radiographs and radionuclide sacroiliac joint uptake ratios were obtained on 14 patients with active systemic lupus erythematosus. Elevated joint ratios were found unilaterally in two patients and bilaterally in seven patients when their lupus was active. In patients whose disease became quiescent, the uptake ratios returned to normal. Two patients had persistently elevated ratios with continued clinical and laboratory evidence of active lupus. Mild sacroiliac joint sclerosis and erosions were detected on pelvic radiographs in these same two patients. Elevated quantitative sacroiliac joint uptake ratios may occur as a manifestation of active systemic lupus erythematosus.

Belimumab Injection

MedlinePlus

... to treat people with certain types of systemic lupus erythematosus (SLE or lupus; an autoimmune disease in which the immune system ... muscle aches; and slow heartbeat.Belimumab helps control lupus but does not cure it. Your doctor will ...

Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in systemic lupus erythematosus (SLE) patients: ethnic differences and potential new targets for therapeutic drugs.

PubMed

Lyn-Cook, Beverly D; Xie, Chenghui; Oates, Jarren; Treadwell, Edward; Word, Beverly; Hammons, George; Wiley, Kenneth

2014-09-01

Increased expression of pro-inflammatory cytokines such as interferon, tumor necrosis factors (TNFs) and specific interleukins (ILs) has been found in a number of autoimmune diseases, including systemic lupus erythematous (SLE). These cytokines are induced by toll-like receptors (TLRs). Toll-like receptors are activated in response to accumulation of apoptotic bodies. These receptors play critical roles in innate immune systems. Increased levels of interferon-alpha (INF-α) have also been found in many SLE patients and often correlate with disease severity. The objectives of this study were to examine the expression of selected TLRs and cytokines that have been identified in animal models and some limited human studies in a group of African Americans (AA) and European Americans (EA) women with lupus in comparison to age-matched non-lupus women. Blood samples were consecutively obtained by informed consent from 286 patients, 153 lupus and 136 non-lupus, seen in the rheumatology clinics at East Carolina University. Cytokines were analyzed from blood serum using enzyme linked immunoassay (ELISA) for IL-6 and INF-α. Total RNA was isolated, using a Paxgene kit, from peripheral blood mononuclear cells of African American and European American women blood samples. Quantitative real-time PCR using the CFX real-time system was conducted on all samples to determine TLRs 7 and 9, as well as INF-α expression. Toll-like receptor 7 (p<0.01) and 9 (p=0.001) expression levels were significantly increased in lupus patients compared to age-matched controls. African American women with lupus had a 2-fold increase in TLR-9 expression level when compared to their healthy controls or European American lupus patients. However, there was no ethnic difference in expression of TLR-7 in lupus patients. INF-α expression was significantly higher in lupus patients (p<0.0001) and also showed ethnic difference in expression. Serum levels revealed significant increases in expression of IL-6, IFN-γ and TNF-α in lupus patients compared to non-lupus patients. African American women with lupus had significantly higher serum levels of IL-6 and TNF-α. African American women with lupus demonstrated increased levels of specific pro-inflammatory cytokines and Toll-like receptors when compared to EA women. Increased expression in these lupus patients provides an opportunity for targeting with antagonist as a new therapy for systemic lupus erythematous. Published by Elsevier Ltd.

A case of systemic lupus erythematosus presenting as bilateral avascular necrosis of femur.

PubMed

Adikari, Madura; Gunawardane, Aloka; Illangantilaka, Sachithra; Atukorale, Himantha; Rubasinghe, Jeevanie

2016-08-05

Avascular necrosis occur as a result of diverse etiology. Chronic inflammatory conditions such as systemic lupus erythematosus considered as a recognize cause. Many cases were reported in systemic lupus erythematosus after treating with corticosteroids. We report a case of a corticosteroid naïve patient presented as bilateral avascular necrosis of femoral head and later progressed to a case of systemic lupus erythematosus. A 26 year old lady presented with right sided hip pain and diagnosed as avascular necrosis of the femoral head. After 6 months she presented a similar pain in left hip, which revealed avascular necrosis of left femoral head as well. A probable cause for her clinical presentation could not be found after extensive clinical and laboratory evaluation. Patient reported high erythrocyte sedimentation rate persistently, and over the next few years progressed as a case of systemic lupus erythematosus. Above case illustrated avascular necrosis could be an early musculoskeletal manifestation of systemic lupus erythematosus even in the absence of corticosteroid administration.

Neurodevelopmental disorders in children born to mothers with systemic lupus erythematosus.

PubMed

Vinet, É; Pineau, C A; Clarke, A E; Fombonne, É; Platt, R W; Bernatsky, S

2014-10-01

Children born to women with systemic lupus erythematosus seem to have a potentially increased risk of neurodevelopmental disorders compared to children born to healthy women. Recent experimental data suggest in utero exposure to maternal antibodies and cytokines as important risk factors for neurodevelopmental disorders. Interestingly, women with systemic lupus erythematosus display high levels of autoantibodies and cytokines, which have been shown, in animal models, to alter fetal brain development and induce behavioral anomalies in offspring. Furthermore, subjects with systemic lupus erythematosus and neurodevelopmental disorders share a common genetic predisposition, which could impair the fetal immune response to in utero immunologic insults. Moreover, systemic lupus erythematosus pregnancies are at increased risk of adverse obstetrical outcomes and medication exposures, which have been implicated as potential risk factors for neurodevelopmental disorders. In this article, we review the current state of knowledge on neurodevelopmental disorders and their potential determinants in systemic lupus erythematosus offspring. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Comparison of estimates of body fat content in childhood-onset systemic lupus erythematosus.

PubMed

Sinicato, N A; Peres, F A; de Oliveira Peliçari, K; de Oliveira Santos, A; Ramos, C D; Marini, R; Appenzeller, S

2017-04-01

Objective We aimed to compare estimates of body fat content with respect to their ability to predict the percentage of body fat, confirmed by dual-energy X-ray absorptiometry scans in childhood-onset systemic lupus erythematosus. Methods We included 64 consecutive childhood-onset systemic lupus erythematosus patients and 64 healthy age and sex-matched controls in a cross-sectional study. Anthropometric data, body mass index and body adiposity index were calculated for all subjects. Childhood-onset systemic lupus erythematosus patients were further assessed for clinical and laboratory childhood-onset systemic lupus erythematosus manifestations and fat mass, lean mass and percentage of body fat evaluated by dual-energy X-ray absorptiometry. Results Elevated waist/hip ratio was observed in childhood-onset systemic lupus erythematosus patients when compared to controls ( p < 0.001). We did not find differences between body mass index and body adiposity index classification in childhood-onset systemic lupus erythematosus patients and controls. Using dual-energy X-ray absorptiometry as gold standard we observed that all indirect estimates of body fat were correlated with whole body fat mass. We observed a correlation between height and cumulative corticosteroid dose adjusted by weight ( r = 0.429, p = 0.005) in childhood-onset systemic lupus erythematosus. On whole body analysis we observed a correlation between lean mass and ACR Damage Index scores ( r = -0.395; p = 0.019); percentage of body fat and adjusted Systemic Lupus Erythematosus Disease Activity Index ( r = 0.402; p = 0.008), disease duration ( r = -0.370; p = 0.012). On trunk analysis we observed a correlation between lean mass and ACR Damage Index ( r = -0.319; p = 0.042); percentage of body fat with adjusted Systemic Lupus Erythematosus Disease Activity Index ( r = 0.402; p = 0.005), disease duration ( r = -0.408; p = 0.005). Conclusions This is the first study analyzing body adiposity index in childhood-onset systemic lupus erythematosus patients. We observed that all indirect estimates of body fat were correlated with whole body fat mass. This study shows that we should not replace body mass index by body adiposity index to evaluating fat levels in childhood-onset systemic lupus erythematosus. In consideration of the importance of overweight classification in cardiovascular diseases, any direct estimates of body fat can be used in an attempt to improve the prognosis of patients. Note We believe that we have presented evidence of body adiposity index accuracy in childhood-onset systemic lupus erythematosus patients but further research on the generalizability of body adiposity index to other patient groups needs to be done.

Living with Lupus (For Parents)

MedlinePlus

... Videos for Educators Search English Español Living With Lupus KidsHealth / For Parents / Living With Lupus What's in ... disease for both doctors and their patients. About Lupus A healthy immune system produces proteins called antibodies ...

THE CAROLINA LUPUS STUDY (CLU)

EPA Science Inventory

Carolina Lupus (CLU) Study, an epidemiologic study of risk factors for systemic lupus erythematosus (SLE). SLE is a severe, chronic, systemic autoimmune disease that disproportionately affects women and African-Americans. The CLU Study focuses on measures of endogenous hormone ex...

Cardiac tamponade as an initial manifestation of systemic lupus erythematosus.

PubMed

Carrion, Diego M; Carrion, Andres F

2012-06-12

Clinical manifestations of pericardial disease may precede other signs and symptoms associated with systemic lupus erythematosus. Although pericardial effusion is one of the most common cardiac problems in patients with systemic lupus erythematosus, haemodynamically significant effusions manifesting as cardiac tamponade are rare and require prompt diagnosis and treatment.

[Peripheral neuropathy in systemic lupus erythematosus with epineural vasculitis and antiphospholipid antibodies].

PubMed

Rafai, M A; Fadel, H; Boulaajaj, F Z; Gam, I; El Moutawakkil, B; Karkouri, M; Hakim, K; Slassi, I

2007-01-01

Neurological manifestations of systemic lupus erythematosus are frequent and polymorphic. Their frequency varies according to authors (24-75p.cent). Central nervous system complications predominate; peripheral features are rare, classically symmetrical polyneuropathy, multiple mononeuropathies or cranial nerve involvement. We report a case of a 48-year-old woman presenting a histologically documented sensitivo-motor polyneuropathy with severe motor involvement complicating lupus associated with antiphospholipides antibodies. Outcome was good after cyclophosphamid pulse. We discuss the frequency of peripheral involvement in systemic lupus erythematosus, pathogenic mechanisms, therapeutic possibilities and outcome of this complication.

Probable systemic lupus erythematosus with cell-bound complement activation products (CB-CAPS).

PubMed

Lamichhane, D; Weinstein, A

2016-08-01

Complement activation is a key feature of systemic lupus erythematosus (SLE). Detection of cell-bound complement activation products (CB-CAPS) occurs more frequently than serum hypocomplementemia in definite lupus. We describe a patient with normocomplementemic probable SLE who did not fulfill ACR classification criteria for lupus, but the diagnosis was supported by the presence of CB-CAPS. © The Author(s) 2016.

Antibodies to native DNA and serum complement (C3) levels. Application to diagnosis and classification of systemic lupus erythematosus.

PubMed

Weinstein, A; Bordwell, B; Stone, B; Tibbetts, C; Rothfield, N F

1983-02-01

The sensitivity and specificity of the presence of antibodies to native DNA and low serum C3 levels were investigated in a prospective study in 98 patients with systemic lupus erythematosus who were followed for a mean of 38.4 months. Hospitalized patients, patients with other connective tissue diseases, and subjects without any disease served as the control group. Seventy-two percent of the patients with systemic lupus erythematosus had a high DNA-binding value (more than 33 percent) initially, and an additional 20 percent had a high DNA-binding value later in the course of the illness. Similarly, C3 levels were low (less than 81 mg/100 ml) in 38 percent of the patients with systemic lupus erythematosus initially and in 66 percent of the patients at any time during the study. High DNA-binding and low C3 levels each showed extremely high predictive value (94 percent) for the diagnosis of systemic lupus erythematosus when applied in a patient population in which that diagnosis was considered. The presence of both abnormalities was 100 percent correct in predicting the diagnosis os systemic lupus erythematosus. Both tests should be included in future criteria for the diagnosis and classification of systemic lupus erythematosus.

Lupus: When the Body Attacks Itself | NIH MedlinePlus the Magazine

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... of this page please turn JavaScript on. Feature: Lupus Lupus: When the Body Attacks Itself Past Issues / Spring 2014 Table of Contents fast facts 1 Lupus occurs when the body's immune system attacks the ...

Population Pharmacokinetic and Pharmacodynamic Analysis of Belimumab Administered Subcutaneously in Healthy Volunteers and Patients with Systemic Lupus Erythematosus.

PubMed

Struemper, Herbert; Thapar, Mita; Roth, David

2017-09-08

Intravenous belimumab 10 mg/kg every 4 weeks is indicated in patients with active, autoantibody-positive systemic lupus erythematosus receiving standard systemic lupus erythematosus care. Subcutaneous 200-mg weekly administration, which may prove more convenient for patients and improve adherence, is currently under investigation. The objective of this study was to characterize the population pharmacokinetics and exposure-efficacy response of subcutaneous belimumab in a pooled analysis of pharmacokinetic data [phase I: BEL114448 (NCT01583530) and BEL116119 (NCT01516450) in healthy subjects (n = 134); phase III: BEL112341 (NCT01484496) in adults with systemic lupus erythematosus (n = 554)] and pharmacodynamic data [BEL112341 in adults with systemic lupus erythematosus (n = 833)]. Non-linear mixed-effects modeling (NONMEM®) was used to develop a population pharmacokinetic model and perform a covariate analysis. Subsequently, exploratory exposure-response analysis and logistic regression modeling was performed based on the individual parameter estimates of the population pharmacokinetic model. Population-pharmacokinetic parameters for subcutaneous belimumab were consistent with those for intravenous belimumab and other immunoglobulin G1 monoclonal antibodies. Pharmacokinetic parameters and subcutaneous belimumab exposure were consistent between healthy subjects and patients with systemic lupus erythematosus, and no evidence for target-mediated disposition of belimumab was found. Subcutaneous belimumab steady-state exposure was achieved after ~11 weeks; subcutaneous belimumab steady-state minimum concentration exceeded that of intravenous belimumab after <4 weeks, and average steady-state concentration was similar to that achieved following intravenous administration. In patients with moderate-to-severe systemic lupus erythematosus, subcutaneous belimumab 200 mg once weekly plus standard of care significantly improved the systemic lupus erythematosus responder index. However, at this dose, the systemic lupus erythematosus responder index response was not significantly associated with belimumab exposure concentrations. The analysis demonstrates that a 200-mg once-weekly dose of belimumab is appropriate for subcutaneous administration in patients with systemic lupus erythematosus and that no dose adjustments are required for adult patients to maintain efficacy and safety.

The management of systemic lupus erythematosus: Facts and controversies.

PubMed

Elbirt, Daniel; Sthoeger, Dalia; Asher, Ilan; Sthoeger, Zev Moshe

2010-01-01

Systemic lupus erythematosus is a multisystem disease of unknown etiology in which dysregulation of the innate and adaptive immune systems has a major effect in the pathogenesis of the disease. The treatment should be tailored for each patient according to how the disease manifests itself. Although there is no cure for systemic lupus erythematosus, the current treatment, using anti-inflammatory, antimalarial, and immunosuppressive agents, is fairly effective, but serious adverse events are possible. New biologic agents that target various components of the immune system recently have been developed for the treatment of patients with systemic lupus erythematosus. Copyright 2010 Elsevier Inc. All rights reserved.

Dyslipidemia in systemic lupus erythematosus: just another comorbidity?

PubMed

Tselios, Konstantinos; Koumaras, Charalambos; Gladman, Dafna D; Urowitz, Murray B

2016-04-01

Among traditional atherosclerotic risk factors, dyslipidemia is believed to decisively affect the long-term prognosis of lupus patients, not only with regard to cardiovascular events but also by influencing other manifestations, such as lupus nephritis. The aim of this study was to review the epidemiology, pathogenesis, evidence for its impact on atherosclerosis manifestations and management of dyslipidemia in lupus patients. English-restricted MEDLINE database search (Medical Subject Headings: lupus or systemic lupus erythematosus and dyslipidemia or hyperlipidemia). The prevalence of dyslipidemia in systemic lupus erythematosus (SLE) ranges from 36% at diagnosis to 60% or even higher after 3 years, depending on definition. Multiple pathogenetic mechanisms are implicated, including antibodies against lipoprotein lipase and cytokines affecting the balance between pro- and anti-atherogenic lipoproteins. Dyslipidemia has a clear impact on clinical cardiovascular disease and surrogate markers for subclinical atherosclerosis. Moreover, it negatively affects end-organ damage (kidneys and brain). Treatment with statins yielded contradictory results as per minimizing cardiovascular risk. Dyslipidemia is a significant comorbidity of lupus patients with multiple negative effects in the long term. Its treatment represents a modifiable risk factor; prompt and adequate treatment can minimize unnecessary burden in lupus patients, thus reducing hospitalizations and their overall morbidity and mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management.

PubMed

Lam, Nguyet-Cam Vu; Ghetu, Maria V; Bieniek, Marzena L

2016-08-15

Systemic lupus erythematosus is an autoimmune disease that affects many systems, including the skin, musculoskeletal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and reproductive systems. Family physicians should be familiar with the manifestations of lupus to aid in early diagnosis, monitoring patients with mild disease, recognizing warning signs that require referral to a rheumatologist, and helping to monitor disease activity and treatment in patients with moderate to severe disease. The American College of Rheumatology has 11 classification criteria for lupus. If a patient meets at least four criteria, lupus can be diagnosed with 95% specificity and 85% sensitivity. All patients with lupus should receive education, counseling, and support. Hydroxychloroquine is the cornerstone of treatment because it reduces disease flares and other constitutional symptoms. Low-dose glucocorticoids can be used to treat most manifestations of lupus. The use of immunosuppressive and cytotoxic agents depends on the body systems affected. Patients with mild disease that does not involve major organ systems can be monitored by their family physician. Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist. To optimize treatment, it is important that a rheumatologist coordinate closely with the patient's family physician to improve chronic care as well as preventive health services.

Case report: disseminated dermatophytosis by microsporum gypseum in a systemic lupus erythematosus patient

PubMed Central

Macêdo, Danielle Patrícia Cerqueira; Neves, Rejane Pereira; Lopes, Flávia Cadengue

2008-01-01

Mycosis is a major contributor to morbidity and mortality in patients with systemic lupus erythematosus and frequent exposition to an infectious source could enhance the development of dermatophytic infections. A case of disseminated dermatophytosis by Microsporum gypseum is reported in a systemic lupus erythematosus (SLE) patient. PMID:24031171

Cardiac tamponade as an initial manifestation of systemic lupus erythematosus

PubMed Central

Carrion, Diego M; Carrion, Andres F

2012-01-01

Clinical manifestations of pericardial disease may precede other signs and symptoms associated with systemic lupus erythematosus. Although pericardial effusion is one of the most common cardiac problems in patients with systemic lupus erythematosus, haemodynamically significant effusions manifesting as cardiac tamponade are rare and require prompt diagnosis and treatment. PMID:22693326

A Case of Systemic Lupus Erythematosus developing Two years after Remission of Thrombotic Thrombocytopenic Purpura

PubMed Central

Myung, Seung-Jae; Yoo, Bin; Lee, Kyoo-Hyung; Yoo, Mi-Ran; Choi, Seung-Won; Yoo, Eun-Sil; Chi, Hyun-Sook; Moon, Hee-Bom

1996-01-01

We describe a 17-year-old male who presented with thrombotic thrombocytopenic purpura (TTP) and 2 years thereafter developed central nervous system lupus and nephritis. The association of TTP and systemic lupus erythematosus has been described, but the unusual sequence and chronological separation is very rare. PMID:8854658

Spontaneous ureteral rupture in a patient with systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, C.H.; Pennebaker, J.B.; Harisdangkul, V.

1983-08-01

A patient with known systemic lupus erythematosus had fever and symptoms of a lower urinary tract infection. Bone scintigraphy showed left ureteral perforation and necrosis with no demonstrable nephrolithiasis. It is speculated that this episode was due to lupus vasculitis.

Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus.

PubMed

Koh, J H; Ko, H S; Kwok, S-K; Ju, J H; Park, S-H

2015-02-01

We investigated the clinical and laboratory characteristics of pregnancies with systemic lupus erythematosus (SLE) and identified lupus flare predictors during pregnancy. Additionally, we examined lupus activity and pregnancy outcomes in SLE patients who continued, discontinued or underwent no hydroxychloroquine (HCQ) treatment during pregnancy. We retrospectively analyzed 179 pregnancies in 128 SLE patients at Seoul St. Mary's Hospital, Korea, between 1998 and 2012 and then assessed the clinical profiles and maternal and fetal outcomes. Overall, 90.5% of pregnancies resulted in a successful delivery and were divided into two groups: those who experienced lupus flares (80 pregnancies, 44.7%) and those who did not (99 pregnancies, 55.3%). Increased preeclampsia, preterm births, low birth weight, intrauterine growth restriction (IUGR), and low 1-minute Apgar scores occurred in pregnancies with lupus flares compared to pregnancies in quiescent disease. Lupus flares were predicted by HCQ discontinuation, a history of lupus nephritis, high pre-pregnancy serum uric acid and low C4 levels. Our study indicates that achieving pre-pregnancy remission and continuing HCQ treatment during pregnancy are important for preventing lupus flares. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Magnetic resonance imaging in neuropsychiatric systemic lupus erythematosus: current state of the art and novel approaches.

PubMed

Postal, M; Lapa, A Tamires; Reis, F; Rittner, L; Appenzeller, S

2017-04-01

Systemic lupus erythematosus is a chronic, inflammatory, immune-mediated disease affecting 0.1% of the general population. Neuropsychiatric manifestations in systemic lupus erythematosus have been more frequently recognized and reported in recent years, occurring in up to 75% of patients during the disease course. Magnetic resonance imaging is known to be a useful tool for the detection of structural brain abnormalities in neuropsychiatric systemic lupus erythematosus patients because of the excellent soft-tissue contrast observed with MRI and the ability to acquire multiplanar images. In addition to conventional magnetic resonance imaging techniques to evaluate the presence of atrophy and white matter lesions, several different magnetic resonance imaging techniques have been used to identify microstructural or functional abnormalities. This review will highlight different magnetic resonance imaging techniques, including the advanced magnetic resonance imaging methods used to determine central nervous system involvement in systemic lupus erythematosus.

A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death.

PubMed

Rosner, S; Ginzler, E M; Diamond, H S; Weiner, M; Schlesinger, M; Fries, J F; Wasner, C; Medsger, T A; Ziegler, G; Klippel, J H; Hadler, N M; Albert, D A; Hess, E V; Spencer-Green, G; Grayzel, A; Worth, D; Hahn, B H; Barnett, E V

1982-06-01

Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group. A total of 222 patients (20%) died. Lupus-related organ system involvement (mainly active nephritis) and infection were the most frequent primary causes of death. Causes of death were similar throughout the followup period. Hemodialysis had little impact on the length of survival for patients with nephritis. Active central nervous system disease and myocardial infarction were infrequent causes of death. There were no deaths from malignancy.

Genetics of SLE: evidence from mouse models.

PubMed

Morel, Laurence

2010-06-01

Great progress has been made in the field of lupus genetics in the past few years, notably with the publication of genome-wide association studies in humans and the identification of susceptibility genes (including Fcgr2b, Ly108, Kallikrein genes and Coronin-1A) in mouse models of spontaneous lupus. This influx of new information has revealed an ever-increasing interdependence between the mouse and human systems for unraveling the genetic basis of lupus susceptibility. Studies in the 1980s and 1990s established that mice prone to spontaneous lupus constitute excellent models of the genetic architecture of human systemic lupus erythematosus (SLE). This notion has been greatly strengthened by the convergence of the functional pathways that are defective in both human and murine lupus. Within these pathways, variants in a number of genes have now been shown to be directly associated with lupus in both species. Consequently, mouse models will continue to serve a pre-eminent role in lupus genetics research, with an increased emphasis on mechanistic and molecular studies of human susceptibility alleles.

The effect of race on incidence and clinical course in systemic lupus erythematosus: The Hopkins Lupus Cohort.

PubMed

Petri, M

1998-01-01

Systemic lupus erythematosus, a chronic autoimmune disease of young women, has a higher incidence and prevalence in African Americans. The Hopkins Lupus Cohort, a prospective longitudinal study of SLE outcomes, has shown that race is a major predictor of clinical manifestations, laboratory and serologic tests, and disease-related morbidity. The effect of race on musculoskeletal morbidity remains even after adjustment for education, insurance status, and smoking.

[Pulmonary manifestations in systemic lupus erythematosus].

PubMed

Vincze, Krisztina; Odler, Balázs; Müller, Veronika

2016-07-01

Systemic lupus erythematosus is the most common connective tissue disease that is associated with pulmonary manifestations. Although lupus has the potential to affect any organ, lung involvement is observed during the course of the disease in most cases and it is prognostic for outcome. Pulmonary manifestations in lupus can be classified into five groups based on the anatomical involvement: pleura, lung parenchyma, bronchi and bronchioli, lung vasculature and respiratory muscles can be involved. The most common respiratory manifestations attributable to lupus are pleuritis with or without pleural effusion, pulmonary vascular disease, upper and lower airway dysfunction, parenchymal disease, and diaphragmatic dysfunction (shrinking lung syndrome). In this article the authors summarize lung involvement of lupus, its diagnosis, therapy and prognosis. Orv. Hetil., 2016, 157(29), 1154-1160.

Toll-like receptor activation in the pathogenesis of lupus nephritis.

PubMed

Lorenz, Georg; Lech, Maciej; Anders, Hans-Joachim

2017-12-01

The pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis is complex but no longer enigmatic. Much progress has been made to on the polygenetic origin of lupus in identifying gene variants that permit the loss of tolerance against nuclear autoantigens. Along the same line in about 50% of lupus patients additional genetic weaknesses promote immune complex glomerulonephritis and filtration barrier dysfunction. Here we briefly summarize the pathogenesis of SLE with a focus on loss of tolerance and the role of toll-like receptors in the "pseudo"-antiviral immunity concept of systemic lupus. In addition, we discuss the local role of Toll-like receptors in intrarenal inflammation and kidney remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells

PubMed Central

Reihl, Alec M.

2016-01-01

Dendritic cells (DC) play an important role in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease with multiple tissue manifestations. In this review, we summarize recent studies on the roles of conventional DC and plasmacytoid DC in the development of both murine lupus and human SLE. In the past decade, studies using selective DC depletions have demonstrated critical roles of DC in lupus progression. Comprehensive in vitro and in vivo studies suggest activation of DC by self-antigens in lupus pathogenesis, followed by breakdown of immune tolerance to self. Potential treatment strategies targeting DC have been developed. However, many questions remain regarding the mechanisms by which DC modulate lupus pathogenesis that require further investigations. PMID:27034965

Neurological Disease in Lupus: Toward a Personalized Medicine Approach.

PubMed

McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P J

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials.

Isolated Tricuspid Valve Libman-Sacks Endocarditis in Systemic Lupus Erythematosus with Secondary Antiphospholipid Syndrome.

PubMed

Unic, Daniel; Planinc, Mislav; Baric, Davor; Rudez, Igor; Blazekovic, Robert; Senjug, Petar; Sutlic, Zeljko

2017-04-01

Libman-Sacks endocarditis, one of the most prevalent cardiac presentations of systemic lupus erythematosus, typically affects the aortic or mitral valve; tricuspid valve involvement is highly unusual. Secondary antiphospholipid syndrome increases the frequency and severity of cardiac valvular disease in systemic lupus erythematosus. We present the case of a 47-year-old woman with lupus and antiphospholipid syndrome whose massive tricuspid regurgitation was caused by Libman-Sacks endocarditis isolated to the tricuspid valve. In addition, we discuss this rare case in the context of the relevant medical literature.

Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.

PubMed

Nagel, J; Saxne, T; Geborek, P; Bengtsson, A A; Jacobsen, S; Svaerke Joergensen, C; Nilsson, J-Å; Skattum, L; Jönsen, A; Kapetanovic, M C

2017-09-01

Background/purpose The objective of this study was to explore the impact of systemic lupus erythematosus and belimumab given in addition to standard of care therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods Forty-seven systemic lupus erythematosus patients and 21 healthy controls were immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty systemic lupus erythematosus patients were treated with traditional disease-modifying anti rheumatic drugs, 11 of those received belimumab in addition, and 32 patients were treated with concomitant prednisolone. Quantification of serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was performed in serum taken before and four to six weeks after vaccination using multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F and 6B were also analyzed using standard enzyme-linked immunosorbent assays. Opsonophagocytic assay was performed on serotype 23F to evaluate the functionality of the antibodies. Pre- and post-vaccination log transformed antibody levels were compared to determine the impact of systemic lupus erythematosus diagnosis and different treatments on antibody response. Results Systemic lupus erythematosus patients as a group showed lower post-vaccination antibody levels and lower fold increase of antibody levels after vaccination compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus erythematosus patients treated with belimumab in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus erythematosus patients. Conclusion Belimumab given in addition to traditional disease-modifying anti rheumatic drugs or prednisolone did not further impair antibody response to 13-valent conjugated pneumococcal vaccine.

The treatment of systemic lupus proliferative nephritis.

PubMed

Punaro, Marilynn G

2013-11-01

Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE) in childhood affecting more than 80% of patients. Treatment of this complication has undergone significant evolution in recent years. A series of randomized controlled trials has clarified the role of a variety of immunomodulating regimens including some novel biologic medications. This review touches on the major trials that have influenced practice and shaped current thinking about the treatment of proliferative lupus glomerulonephritis.

75 FR 26266 - National Cancer Institute (NCI); National Institute of Allergy and Infectious Diseases (NIAID...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-11

... collaboration with the Lupus Foundation of America, Washington, DC, will hold a scientific conference. Title: ``Systemic Lupus Erythematosus: From Mouse Models to Human Disease and Treatment.'' Dates: September 2-3... disease relevant to lupus together with clinicians treating lupus patients. There are numerous mouse...

Breastfeeding in mothers with systemic lupus erythematosus.

PubMed

Noviani, M; Wasserman, S; Clowse, M E B

2016-08-01

Breastfeeding is known to improve the well-being of a mother and her infant, and about half of all new mothers breastfeed, but it is unknown how breastfeeding is pursued in systemic lupus erythematosus (SLE; lupus) patients. We sought to determine the rate of breastfeeding and the factors influencing this among women with lupus. In addition, we reassessed the current safety data in lactation of lupus medications. Data were collected from lupus patients enrolled in a prospective registry who fulfilled the 2012 SLICC criteria, had a live birth, and for whom postpartum breastfeeding status was known. Data included physician assessments of lupus activity and medications, breastfeeding intentions during pregnancy and practice following pregnancy. The safety of medications in breastfed infants was assessed through a comprehensive review of LactMed, a national database about medications in lactation. A total of 51 pregnancies in 84 women with lupus were included in the study. Half of the lupus patients (n = 25, 49%) chose to breastfeed. The rate of breastfeeding was not significantly affected by socioeconomic factors. In contrast, low postpartum lupus activity, term delivery, and a plan to breastfeed early in pregnancy were significantly associated with breastfeeding in lupus patients. In reviewing the most up-to-date data, the majority of lupus medications appear to have very minimal transfer into breast milk and are likely compatible with breastfeeding. Half of women with lupus breastfed and most desire to breastfeed. Hydroxychloroquine, azathioprine, methotrexate, and prednisone have very limited transfer into breast milk and may be continued while breastfeeding. © The Author(s) 2016.

Unusual presentation of childhood Systemic Lupus Erythematosus

PubMed Central

Kumar, Sathish; Agarwal, Indira

2007-01-01

Bullous systemic lupus erythematosus is a rare blistering condition with a distinctive combination of clinical, histological and immunopathologic features that together constitute a unique bullous disease phenotype. It is often associated with autoimmunity to type VII collagen. Here we report a child who presented with bullous systemic lupus erythematosus. Rapid resolution of the blisters occurred following treatment with dapsone. PMID:18028550

Murine Models of Systemic Lupus Erythematosus

PubMed Central

Perry, Daniel; Sang, Allison; Yin, Yiming; Zheng, Ying-Yi; Morel, Laurence

2011-01-01

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder. The study of diverse mouse models of lupus has provided clues to the etiology of SLE. Spontaneous mouse models of lupus have led to identification of numerous susceptibility loci from which several candidate genes have emerged. Meanwhile, induced models of lupus have provided insight into the role of environmental factors in lupus pathogenesis as well as provided a better understanding of cellular mechanisms involved in the onset and progression of disease. The SLE-like phenotypes present in these models have also served to screen numerous potential SLE therapies. Due to the complex nature of SLE, it is necessary to understand the effect specific targeted therapies have on immune homeostasis. Furthermore, knowledge gained from mouse models will provide novel therapy targets for the treatment of SLE. PMID:21403825

Study of audiovestibular dysfunction in children with systemic lupus erythematosus.

PubMed

Gad, Ghada Ibrahim; Mohamed, Somaia Tawfik; Awwad, Khaled Salah; Mohamed, Rehab Fetoh

2013-09-01

Inner ear dysfunction in systemic lupus erythematosis patients has been reported but audiovestibular involvement is not well documented especially in pediatrics. This study was designed to evaluate silent audiovestibular dysfunction among SLE children. Case control study examined in allergy and immunology clinic; pediatrics hospital and audiovestibular clinic; Ain Shams University from January 2009 to December 2010. Thirty-five systemic lupus erythematosus children (diagnosed according to American College of Rheumatology); age group 8-16 years, were randomly selected. Five of them were excluded due to one or more exclusion criteria (previous otitis media, stroke, lupus cerebritis, meningitis or encephalitis, audiovestibular symptom). Ten of them refused enrollment or could not complete full battery. Seventeen females and three males, mean age 12.9 ± 2.6 years, completed the study. Control group included 20 normal subjects, age and sex matched. Full clinical assessment, basic audiological evaluation and vestibular testing (videonystagmography VNG and computerized dynamic posturography CDP) were conducted for children included in the study. Five systemic lupus erythematosus patients had sensorineural hearing loss strongly associated with +ve antiphospholipid antibody and two had conductive hearing loss. Two children in control group had conductive hearing loss (p=0.05). Abnormal VNG findings was significantly higher among systemic lupus erythematosus children (40%) compared to controls (0%) and associated with +ve antiphospholipid antibodies (χ(2)=10, p=0.002, Fisher exact test=0.003). Twenty-five percentage of systemic lupus erythematosus children had abnormal CDP findings reflecting impaired balance function associated with positive antiphospholipid antibodies showing significant statistical difference compared to controls (0% affection) (χ(2)=5.7, p=0.017, Fisher exact test=0.047). Silent audiovestibular dysfunction is prevalent among systemic lupus erythematosus children especially those positive for antiphospholipid antibodies necessitating routine regular evaluation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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2012-03-30

... Treatment of Lupus Nephritis Description of Technology: Systemic lupus erythematosus (SLE) is a multi-organ... Commercial Applications: Further research and development of therapeutic approach to treat lupus nephritis...

Neurological Disease in Lupus: Toward a Personalized Medicine Approach

PubMed Central

McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P. J.

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials. PMID:29928273

Mucocutaneous manifestations in juvenile-onset systemic lupus erythematosus: a review of literature.

PubMed

Chiewchengchol, Direkrit; Murphy, Ruth; Edwards, Steven W; Beresford, Michael W

2015-01-01

Patients diagnosed with juvenile-onset systemic lupus erythematosus (JSLE) often have skin and oral lesions as part of their presentation. These mucocutaneous lesions, as defined by the American College of Rheumatology (ACR) in 1997, include malar rash, discoid rash, photosensitivity and oral ulcers. It is therefore essential to recognize mucocutaneous lesions to accurately diagnose JSLE. The mucocutaneous lesions can be divided into those with classical histological features (LE specific) and those strongly associated with and forming part of the diagnostic spectrum, but without the classical histological changes of lupus (LE nonspecific). A malar rash is the most commonly associated LE specific dermatological presentation. This skin manifestation is an acute form and also correlates with disease activity. Subacute (polycyclic or papulosquamous lesions) and chronic (discoid lesions) forms, whilst showing classical histological changes supportive of lupus, are less commonly associated with systemic lupus and do not correlate with disease activity. The most commonly associated skin lesions without classical lupus changes are cutaneous vasculitis, oral ulcers and diffuse non-scarring alopecia. These signs frequently relate to disease activity. An understanding of cutaneous signs and symptoms of lupus in children is important to avoid delay in diagnosis. They will often improve as lupus is adequately controlled and their reappearance is often the first indicator of a disease flare.

Designing an Intervention for Women with Systemic Lupus Erythematosus from Medically Underserved Areas to Improve Care: A Qualitative Study

PubMed Central

Feldman, Candace H; Bermas, Bonnie L; Zibit, Melanie; Fraser, Patricia; Todd, Derrick J; Fortin, Paul R; Massarotti, Elena; Costenbader, Karen H

2013-01-01

Objective Systemic lupus erythematosus (lupus) disproportionately affects women, racial/ethnic minorities and low-income populations. We held focus groups for women from medically underserved communities to discuss interventions to improve care. Methods From our Lupus Registry, we invited 282 women, > 18 years, residing in urban, medically underserved areas. Hospital-based clinics and support groups also recruited participants. Women were randomly assigned to 3 focus groups. 75-minute sessions were recorded, transcribed and coded thematically using interpretative phenomenologic analysis and single counting methods. We categorized interventions by benefits, limitations, target populations and implementation questions. Results 29 women with lupus participated in 3 focus groups, (n=9, 9, 11). 80% were African American and 83% were from medically underserved zip codes. Themes included the desire for lupus education, isolation at the time of diagnosis, emotional and physical barriers to care, and the need for assistance navigating the healthcare system. 20 of 29 participants (69%) favored a peer support intervention; 17 (59%) also supported a lupus health passport. Newly diagnosed women were optimal intervention targets. Improvements in quality of life and mental health were proposed outcome measures. Conclusion Women with lupus from medically underserved areas have unique needs best addressed with an intervention designed through collaboration between community members and researchers. PMID:23087258

Bilateral periorbital edema in systemic lupus erythematosus.

PubMed

Norden, D; Weinberg, J; Schumacher, H R; Keenan, G; Freundlich, B

1993-12-01

Periorbital edema is a rare manifestation of systemic lupus erythematosus (SLE). We describe a patient with SLE who developed bilateral periorbital edema during her lupus flares. Conjunctival biopsy confirmed the presence of inflammation. Resolution occurred only after high doses of corticosteroids. The differential diagnosis of periorbital edema and possible etiologies of the edema are briefly discussed.

[Systemic lupus erythematosus masking the acquired immunodeficiency syndrome. A report on four cases].

PubMed

Kotyla, Przemysław; Kucharz, Eugeniusz J

2012-01-01

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease of connective tissue with an unknown etiology and a rich clinical picture with involvement of multiple organs. Given the rich symptomatology, application of the current classification criteria is associated with a significant risk of attributing symptoms of other pathologies to lupus and/or other connective tissue disease. Inherited and acquired immune deficiencies may sometimes demonstrate a lupus-like clinical symptomatology. In this work we reviewed 4 of cases referred to the Department of Internal Diseases and Rheumatology of the Silesian Medical University in Katowice with suspected or confirmed systemic lupus erythematosus. A positive anti-HIV antibody test led to the diagnosis of the acquired immunodeficiency syndrome (AIDS). Due to the close similarity of the clinical picture and the presence of antinuclear antibodies in both diseases, the authors postulate that the anti-HIV antibody test should be done routinely in patients with connective tissue diseases.

Cutaneous manifestations of systemic lupus erythematosus in a tertiary referral center.

PubMed

Kole, Alakes Kumar; Ghosh, Alakendu

2009-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement. The skin is the second most commonly affected organ. SLE with skin lesions can produce considerable morbidity resulting from painful skin lesions, alopecia, disfigurement, etc. Skin lesions in patients with lupus may be specific (LE specific) or may be non specific (LE non specific). Acute cutaneous LE (Lupus specific) has a strong association with systemic disease and non-specific skin lesions always indicate disease activity for which patients present to rheumatologists and internists. Therefore, a thorough understanding of the cutaneous manifestations of SLE is essential for most efficient management. The aims of this study were to evaluate the patterns and prevalence of skin lesions in patients with SLE and to assess the relationship between skin lesions and other systemic involvement. At the Department of Rheumatology and Clinical Immunology, IPGME&R in Kolkata, 150 patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatology Association (updated 1982) were examined and followed-up for cutaneous manifestations between January 2002 and January 2007. Skin lesions were important clinical features. About 45 patients (30%) presented with skin lesions although all patients had skin lesions during the follow-up period. Skin changes noted were as follows: Lupus specific lesions: malar rash in 120 patients (80%), photosensitive dermatitis in 75 patients (50%), generalized maculopapular rash in 40 patients (26.67%), discoid rash in 30 patients (20%), subacute cutaneous lupus erythematosus (SCLE) in 5 patients (3.34%), lupus profundus in 5 patients (3.34%). The lupus non-specific lesions were non-scarring alopecia in 130 patients (86.67%), oral ulcers in 85 patients (56.67%), vasculitic lesions in 50 patients (33.34%), bullous lesions in 15 patients (10%), Raynaud's phenomenon in 10 patients (6.67%), pyoderma gangrenosum in 2 patients (1.34%), erythema multiforme in 10 patients (6.67%), and nail fold infarcts in 2 patients (1.34%); however, mucosal discoid lupus, lichenoid discoid lupus, livedo reticularis, sclerodactyly, etc. were not detected. Patients having lupus-specific skin lesions e.g., malar rash were associated with systemic involvement, whereas those having lupus non-specific skin lesions were associated with disease flare. Skin lesions in patients with SLE are important disease manifestations and proper understanding is essential for diagnosis and efficient management.

Indications for colonoscopy in patients with systemic lupus erythematosus.

PubMed

Iwamuro, Masaya; Okada, Hiroyuki; Kato, Jun; Tanaka, Takehiro; Sada, Ken-Ei; Makino, Hirofumi; Yamamoto, Kazuhide

2013-01-01

Systemic lupus erythematosus is a systemic autoimmune disorder that sometimes involves the gastrointestinal tract. The aim of this study is to describe the clinical characteristics of patients with systemic lupus erythematosus with colorectal involvement, and to provide criteria for colonoscopy. Among 288 patients with systemic lupus erythematosus, 29 patients underwent colonoscopy. The clinical backgrounds were comparatively analyzed between the patients with colorectal involvements (n = 11, group A) and the patients without colorectal involvements (n = 18, group B). Endoscopic features were also evaluated in group A patients. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) of the group A patients was higher than that of the group B patients. Abdominal pain (n = 6) and diarrhea (n = 5) were significantly correlated with the presence of colorectal involvements, and other manifestations in group A patients included visible blood in stools (n = 5) and fever (n = 1). In colonoscopy, discrete ulcers (n = 5), longitudinal ulcers (n = 1), erosions and/or small ulcers (n = 2), edematous mucosa (n = 2), and concurrent ulcerative colitis (n = 1) were identified. Patients with systemic lupus erythematosus with SLEDAI scores > or = 5, or with gastrointestinal symptoms, particularly those who present with abdominal pain or diarrhea should undergo colonoscopy, because these patients are likely to have mucosal damage in the colorectum.

The rate of and risk factors for frequent hospitalization in systemic lupus erythematosus: results from the Korean lupus network registry.

PubMed

Lee, J W; Park, D J; Kang, J H; Choi, S E; Yim, Y R; Kim, J E; Lee, K E; Wen, L; Kim, T J; Park, Y W; Sung, Y K; Lee, S S

2016-11-01

Objectives The survival rate of patients with systemic lupus erythematosus has improved in the last few decades, but the rate of hospitalization and health care costs for these patients remain higher than in the general population. Thus, we evaluated the rate of hospitalization and associated risk factors in an inception cohort of Korean patients with lupus. Methods Of the 507 patients with systemic lupus erythematosus enrolled in the KORean lupus NETwork, we investigated an inception cohort consisting of 196 patients with systemic lupus erythematosus presenting within 6 months of diagnosis based on the American College of Rheumatology classification criteria. We evaluated the causes of hospitalization, demographic characteristics, and laboratory and clinical data at the time of systemic lupus erythematosus diagnosis of hospitalized patients and during a follow-up period. We calculated the hospitalization rate as the number of total hospitalizations divided by the disease duration, and defined "frequent hospitalization" as hospitalization more than once per year. Results Of the 196 patients, 117 (59.6%) were admitted to hospital a total of 257 times during the 8-year follow-up period. Moreover, 22 (11.2%) patients were hospitalized frequently. The most common reasons for hospitalization included disease flares, infection, and pregnancy-related morbidity. In the univariate regression analysis, malar rash, arthritis, pericarditis, renal involvement, fever, systemic lupus erythematosus disease activity index > 12, hemoglobin level < 10 mg/dl, albumin level < 3.5 mg/dl, and anti-Sjögren's syndrome A positivity were associated with frequent hospitalization. Finally, multivariate analysis showed that arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization. Conclusions Our results showed that frequent hospitalization occurred in 11.2% of hospitalized patients and arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization.

Clinical practice guidelines for the treatment of systemic lupus erythematosus by the Mexican College of Rheumatology.

PubMed

Xibillé-Friedmann, Daniel; Pérez-Rodríguez, Marcela; Carrillo-Vázquez, Sandra; Álvarez-Hernández, Everardo; Aceves, Francisco Javier; Ocampo-Torres, Mario C; García-García, Conrado; García-Figueroa, José Luis; Merayo-Chalico, Javier; Barrera-Vargas, Ana; Portela-Hernández, Margarita; Sicsik, Sandra; Andrade-Ortega, Lilia; Rosales-Don Pablo, Víctor Manuel; Martínez, Aline; Prieto-Seyffert, Pilar; Pérez-Cristóbal, Mario; Saavedra, Miguel Ángel; Castro-Colín, Zully; Ramos, Azucena; Huerta-Sil, Gabriela; Hernández-Cabrera, María Fernanda; Jara, Luis Javier; Limón-Camacho, Leonardo; Tinajero-Nieto, Lizbet; Barile-Fabris, Leonor A

2018-05-04

There are national and international clinical practice guidelines for systemic lupus erythematosus treatment. Nonetheless, most of them are not designed for the Mexican population or are devoted only to the treatment of certain disease manifestations, like lupus nephritis, or are designed for some physiological state like pregnancy. The Mexican College of Rheumatology aimed to create clinical practice guidelines that included the majority of the manifestations of systemic lupus erythematosus, and also incorporated guidelines in controversial situations like vaccination and the perioperative period. The present document introduces the «Clinical Practice Guidelines for the Treatment of Systemic Lupus Erythematosus» proposed by the Mexican College of Rheumatology, which could be useful mostly for non-rheumatologist physicians who need to treat patients with systemic lupus erythematosus without having the appropriate training in the field of rheumatology. In these guidelines, the reader will find recommendations on the management of general, articular, kidney, cardiovascular, pulmonary, neurological, hematologic and gastrointestinal manifestations, and recommendations on vaccination and treatment management during the perioperative period. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

Coagulation cascade and complement system in systemic lupus erythematosus

PubMed Central

Liang, Yan; Xie, Shang-Bo; Wu, Chang-Hao; Hu, Yuan; Zhang, Qin; Li, Si; Fan, Yin-Guang; Leng, Rui-Xue; Pan, Hai-Feng; Xiong, Hua-Bao; Ye, Dong-Qing

2018-01-01

This study was conducted to (1) characterize coagulation cascade and complement system in systemic lupus erythematosus (SLE); (2) evaluate the associations between coagulation cascade, complement system, inflammatory response and SLE disease severity; (3) test the diagnostic value of a combination of D-dimer and C4 for lupus activity. Transcriptomics, proteomics and metabolomics were performed in 24 SLE patients and 24 healthy controls. The levels of ten coagulations, seven complements and three cytokines were measured in 112 SLE patients. Clinical data were collected from 2025 SLE patients. The analysis of multi-omics data revealed the common links for the components of coagulation cascade and complement system. The results of ELISA showed coagulation cascade and complement system had an interaction effect on SLE disease severity, this effect was pronounced among patients with excess inflammation. The analysis of clinical data revealed a combination of D-dimer and C4 provided good diagnostic performance for lupus activity. This study suggested that coagulation cascade and complement system become ‘partners in crime’, contributing to SLE disease severity and identified the diagnostic value of D-dimer combined with C4for lupus activity. PMID:29599912

Clinical and immunological characteristics of 150 systemic lupus erythematosus patients in Jamaica: a comparative analysis.

PubMed

Maloney, K C; Ferguson, T S; Stewart, H D; Myers, A A; De Ceulaer, K

2017-11-01

Background Epidemiological studies in systemic lupus erythematosus have been reported in the literature in many countries and ethnic groups. Although systemic lupus erythematosus in Jamaica has been described in the past, there has not been a detailed evaluation of systemic lupus erythematosus patients in urban Jamaica, a largely Afro-Caribbean population. The goal of this study was to describe the clinical features, particularly disease activity, damage index and immunological features, of 150 systemic lupus erythematosus subjects. Methods 150 adult patients (≥18 years) followed in rheumatology clinic at a tertiary rheumatology hospital centre (one of two of the major public referral centres in Jamaica) and the private rheumatology offices in urban Jamaica who fulfilled Systemic Lupus International Collaborating Clinics (SLICC) criteria were included. Data were collected by detailed clinical interview and examination and laboratory investigations. Hence demographics, SLICC criteria, immunological profile, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and SLICC/American College of Rheumatology (ACR) damage index (SDI) were documented. Results Of the 150 patients, 145 (96.7%) were female and five (3.3%) were male. The mean age at systemic lupus erythematosus onset was 33.2 ± 10.9. Mean disease duration was 11.3 ± 8.6 years. The most prevalent clinical SLICC criteria were musculoskeletal, with 141 (94%) of subjects experiencing arthralgia/arthritis, followed by mucocutaneous manifestations of alopecia 103 (68.7%) and malar rash 46 (30.7%), discoid rash 45 (30%) and photosensitivity 40 (26.7%). Lupus nephritis (biopsy proven) occurred in 42 (28%) subjects and 25 (16.7%) met SLICC diagnostic criteria with only positive antinuclear antibodies/dsDNA antibodies and lupus nephritis on renal biopsy. The most common laboratory SLICC criteria were positive antinuclear antibodies 136 (90.7%) followed by anti-dsDNA antibodies 95 (63.3%) and low complement (C3) levels 38 (25.3%). Twenty-seven (18%) met SLICC diagnostic criteria with only positive antinuclear antibodies/anti-dsDNA antibodies and lupus nephritis on renal biopsy. Mean SLEDAI score was 6.9 ± 5.1 with a range of 0-32. Organ damage occurred in 129 (86%) patients; mean SDI was 2.4 ± 1.8, with a range of 0-9. Conclusion These results are similar to the clinical manifestations reported in other Afro-Caribbean populations; however, distinct differences exist with respect to organ involvement and damage, particularly with respect to renal involvement, which appears to be reduced in our participants.

Lupus pneumonitis as the initial presentation of systemic lupus erythematosus: case series from a single institution.

PubMed

Wan, S A; Teh, C L; Jobli, A T

2016-11-01

Objective The aim of this study was to examine the clinical features, treatment and outcome of systemic lupus erythematosus (SLE) patients in our centre who presented with lupus pneumonitis as the initial manifestation. Methods We performed a retrospective review of all patients who presented with lupus pneumonitis during the initial SLE manifestation from March 2006 to March 2015. Results There were a total of five patients in our study who presented with fever and cough as the main clinical features. All patients had pulmonary infiltrates on chest radiographs. High-resolution computed tomography, which was performed in two patients, showed ground glass opacities with patchy consolidations bilaterally. All patients received high-dose steroids, 80% received intravenous cyclophosphamide and 60% received intravenous immunoglobulin. Two patients died from severe lupus pneumonitis within 2 weeks of admission despite treatment with ventilation, steroids, cyclophosphamide and intravenous immunoglobulin. Conclusions Acute lupus pneumonitis is an uncommon presentation of SLE. Mortality in this case series is 40%.

Lupus cystitis in Korean patients with systemic lupus erythematosus: risk factors and clinical outcomes.

PubMed

Koh, J H; Lee, J; Jung, S M; Ju, J H; Park, S-H; Kim, H-Y; Kwok, S-K

2015-10-01

This study was performed to investigate the clinical characteristics of lupus cystitis and determine the risk factors and clinical outcomes of lupus cystitis in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed 1064 patients at Seoul St. Mary's Hospital in Seoul, Korea, from 1998 to 2013. Twenty-four patients had lupus cystitis. Lupus cystitis was defined as unexplained ureteritis and/or cystitis as detected by imaging studies, cystoscopy, or bladder histopathology without urinary microorganisms or stones. Three-fourths of patients with lupus cystitis had concurrent lupus mesenteric vasculitis (LMV). The initial symptoms were gastrointestinal in nature for most patients (79.2%). High-dose methylprednisolone was initially administered to most patients (91.7%) with lupus cystitis. Two patients (8.3%) died of urinary tract infections. Sixty-five age- and sex-matched patients with SLE who were admitted with other manifestations were included as the control group. Patients with lupus cystitis showed a lower C3 level (p = 0.031), higher SLE Disease Activity Index score (p = 0.006), and higher ESR (p = 0.05) upon admission; more frequently had a history of LMV prior to admission (p < 0.001); and less frequently had a history of neuropsychiatric lupus (p = 0.031) than did patients with SLE but without lupus cystitis. The occurrence of lupus cystitis was associated with a history of LMV (OR, 21.794; 95% CI, 4.061-116.963). The median follow-up period was 3.4 years, and the cumulative one-year mortality rate was 20%. Complications developed in 33.3% of patients with lupus cystitis and were related to survival (log-rank p = 0.021). Our results suggest that the possibility of lupus cystitis should be considered when a patient with SLE and history of LMV presents with gastrointestinal symptoms or lower urinary tract symptoms. Development of complications in patients with lupus cystitis can be fatal. Thus, intensive treatment and follow-up are needed, especially in the presence of complications. © The Author(s) 2015.

Immune Cell Metabolism in Systemic Lupus Erythematosus.

PubMed

Choi, Seung-Chul; Titov, Anton A; Sivakumar, Ramya; Li, Wei; Morel, Laurence

2016-11-01

Cellular metabolism represents a newly identified checkpoint of effector functions in the immune system. A solid body of work has characterized the metabolic requirements of normal T cells during activation and differentiation into polarized effector subsets. Similar studies have been initiated to characterize the metabolic requirements for B cells and myeloid cells. Only a few studies though have characterized the metabolism of immune cells in the context of autoimmune diseases. Here, we review what is known on the altered metabolic patterns of CD4 + T cells, B cells, and myeloid cells in lupus patients and lupus-prone mice and how they contribute to lupus pathogenesis. We also discuss how defects in immune metabolism in lupus can be targeted therapeutically.

Systemic lupus erythematosus diagnostics in the ‘omics’ era

PubMed Central

Arriens, Cristina; Mohan, Chandra

2014-01-01

Systemic lupus erythematosus is a complex autoimmune disease affecting multiple organ systems. Currently, diagnosis relies upon meeting at least four out of eleven criteria outlined by the ACR. The scientific community actively pursues discovery of novel diagnostics in the hope of better identifying susceptible individuals in early stages of disease. Comprehensive studies have been conducted at multiple biological levels including: DNA (or genomics), mRNA (or transcriptomics), protein (or proteomics) and metabolites (or metabolomics). The ‘omics’ platforms allow us to re-examine systemic lupus erythematosus at a greater degree of molecular resolution. More importantly, one is hopeful that these ‘omics’ platforms may yield newer biomarkers for systemic lupus erythematosus that can help clinicians track the disease course with greater sensitivity and specificity. PMID:24860621

Lupus nephritis: current update

PubMed Central

2011-01-01

Lupus nephritis is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. The general consensus is that 60% of lupus patients will develop clinically relevant nephritis at some time in the course of their illness. Prompt recognition and treatment of renal disease is important, as early response to therapy is correlated with better outcome. The present review summarizes our current understanding of the pathogenic mechanisms underlying lupus nephritis and how the disease is currently diagnosed and treated. PMID:22078716

Acute acalculous cholecystitis in systemic lupus erythematosus: a rare initial manifestation.

PubMed

Manuel, Valdano; Pedro, Gertrudes Maria; Cordeiro, Lemuel Bornelli; de Miranda, Sandra Maria da Rocha Neto

2016-01-01

Acute acalculous cholecystitis is a very rare gastrointestinal manifestation in systemic lupus erythematosus and becomes rarer as an initial manifestation. There are only two cases reported. The authors report a 20-year-old black woman that presented acute acalculous cholecystitis revealed by abdominal computed tomography. During hospitalization, she was diagnosed systemic lupus erythematosus. Conservative treatment with antibiotics was performed with complete remission of the symptoms. Corticosteroid was started in ambulatory. Cholecystectomy has been the treatment of choice in acute acalculous cholecystitis as a complication of systemic lupus erythematosus. The patient responded well to conservative treatment, and surgery was not required. This case is unique in the way that corticosteroid was started in ambulatory care. We should not forget that the acute acalculous cholecystitis can be the initial presentation of systemic lupus erythematosus although its occurrence is very rare. Conservative treatment should be considered. Abdominal computed tomography was a determinant exam for better assessment of acute acalculous cholecystitis. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Amelioration of systemic lupus erythematosus by Withangulatin A in MRL/lpr mice.

PubMed

Sun, Lijuan; Zhou, Lin; Chen, Mingcang; Zhong, Renqian; Liu, Jianwen

2011-09-01

We have previously reported the anti-inflammatory potential and the possible underlying mechanisms of Withangulatin A (WA), which is an active component isolated from Physalis angulata L. Here, we demonstrated that WA might improve the life quality, as well as reduced the accumulation of proteinuria symptoms and levels of anti-double-stranded DNA antibodies in MRL/lpr mice. Moreover, WA could improve renal histopathologic characteristics of MRL/lpr mice. Intriguingly, expression of B cell-activating factor (BAFF), BAFF-R and related gene in the spleen were significantly reduced in 10 mg/kg WA-treated mice compared with that in 5 mg/kg WA-treated mice and untreated mice. These findings indicate that WA might have a pleiotropic therapeutic effect through their immunosuppression via inhibiting BAFF signaling, which suggest a potential application of this active constituent in the treatment of SLE. Copyright © 2011 Wiley-Liss, Inc.

Spontaneous tendon rupture in systemic lupus erythematosus: association with Jaccoud's arthropathy.

PubMed

Alves, E M; Macieira, J C; Borba, E; Chiuchetta, F A; Santiago, M B

2010-03-01

Tendon rupture has rarely been described in patients with systemic lupus erythematosus. From observation of three cases of Jaccoud's arthropathy with tendon rupture, and considering that this arthropathy is more related to an inflammatory process of the tendon sheath than to synovitis per se, the intention of this study was to review the cases of tendon rupture in patients with systemic lupus erythematosus, in the hope of determining the frequency of Jaccoud's arthropathy associated with this complication. Systematic review using MEDLINE, Scielo and LILACS databases (1966 to 2009) and the following keywords: systemic lupus erythematosus, tendon rupture, Jaccoud's arthropathy. Secondary references were additionally obtained. Additionally, three Brazilian systemic lupus erythematosus patients who developed tendon rupture are described. Only 40 articles obtained fulfilled the previously established criteria. They were all case reports; the number of cases reported was 52 which, together with the three cases presented herein add up to 55 cases. Forty-six patients were women aged between 19 and 71 years, with a mean age of 40.1 +/- 12.4 years, and the average duration of the disease was 10 years. The most frequently observed rupture sites were the patellar and Achilles' tendons. While almost all patients described were on various doses of corticosteroids, 16 patients concomitantly had Jaccoud's arthropathy (29%). In conclusion, the association between Jaccoud's arthropathy and tendon rupture in systemic lupus erythematosus has been underestimated. As almost one-third of the systemic lupus erythematosus patients with tendon rupture also have Jaccoud's arthropathy, this arthropathy may be recognized as risk marker for tendon rupture.

Functional Connectivity Changes in Systemic Lupus Erythematosus: A Resting-State Study.

PubMed

Nystedt, Jessika; Mannfolk, Peter; Jönsen, Andreas; Bengtsson, Anders; Nilsson, Petra; Sundgren, Pia C; Strandberg, Tor O

2018-05-01

To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.

Auricular chondritis and thrombotic microangiopathy: an unusual combination revealing systemic lupus erythematosus.

PubMed

Bellon, Nathalia; Anguel, Nadia; Vandendries, Christophe; Goujard, Cecile; Lambotte, Olivier

2013-07-01

Thrombotic microangiopathy is a severe disorder, which is a cause of stroke in young patients. Etiologic investigations are mandatory to diagnose underlying disease. Systemic lupus erythematosus is one of the diseases, which can be associated with thrombotic microangiopathy. Although lupus diagnosis is usually easy, relying on characteristic clinical manifestations, rare symptoms can be misinterpreted. We report here a case of polychondritis, which was the first manifestation of a lupus-associated thrombotic microangiopathy. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Recent Advances in the Immunopathogenesis of Systemic Lupus Erythematosus

PubMed Central

Bardana, Emil J.; Pirofsky, Bernard

1975-01-01

Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disease having definite etiologic associations with ethnic, genetic, viral and immunologic factors. Its pathologic hallmark, vasculitis, is currently felt to be the end result of an immune-complex mechanism. Several clinical and serologic variants of SLE are recognized including discoid lupus erythematosus (DLE), mixed connective tissue disease (MCTD) and drug-induced equivalents—such as procainamide-induced lupus (PIL). The distinguishing features of these variants as well as their prognosis and therapy are discussed in relation to recent developments in the immunopathogenesis of SLE. PMID:46657

Risk of autism spectrum disorder in children born to mothers with systemic lupus erythematosus and rheumatoid arthritis in Taiwan.

PubMed

Tsai, Ping-Han; Yu, Kuang-Hui; Chou, I-Jun; Luo, Shue-Fen; Tseng, Wen-Yi; Huang, Lu-Hsiang; Kuo, Chang-Fu

2017-11-26

To determine whether offspring of Taiwanese mothers with systemic lupus erythematosus or rheumatoid arthritis have a higher risk of autism spectrum disorder. Using the National Health Insurance database and National Birth Registry, we identified a cohort of all live births in Taiwan between 2001 and 2012. Children born to mothers with systemic lupus erythematosus or rheumatoid arthritis were identified and matched with up to 8 controls by maternal age, 1-minute Apgar score, 5-minute Apgar score, mode of delivery, sex of the child, gestational age, birth weight and place of residence. Marginal Cox proportional hazard models were used to estimate relative risk (RR) with 95% confidence intervals (CI) for ASD in offspring. Of 1,893,244 newborns, 0.08% (n=1594) were born to systemic lupus erythematosus mothers, and 0.04% (n=673) were born to rheumatoid arthritis mothers. Overall, 5 of 673 (0.74%) offspring of rheumatoid arthritis mothers, 7 of 1594 (0.44%) offspring of systemic lupus erythematosus mothers and 10,631 of 1,893,244 (0.56%) offspring of all mothers developed autism spectrum disorder. Autism spectrum disorder incidence (per 100,000 person-years) was 140.39 (95% CI, 45.58-327.62) for the rheumatoid arthritis group and 76.19 (95% CI, 30.63-156.97) for the systemic lupus erythematosus group. Autism spectrum disorder risk was not significantly higher for children born to mothers with rheumatoid arthritis (HR, 1.42; 95% CI, 0.60-3.40) or systemic lupus erythematosus (HR, 0.76; 95% CI, 0.36-1.59). Children born to women with systemic lupus erythematosus or rheumatoid arthritis do not have a higher risk of autism spectrum disorder. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Validation of the LupusPRO version 1.8: an update to a disease-specific patient-reported outcome tool for systemic lupus erythematosus.

PubMed

Azizoddin, D R; Weinberg, S; Gandhi, N; Arora, S; Block, J A; Sequeira, W; Jolly, M

2018-04-01

Objectives LupusPRO has shown good measurement properties as a disease-specific patient-reported outcome tool in systemic lupus erythematosus (SLE). For the purpose of clinical trials, the version 1.7 (v1.7) domain of Pain-Vitality was separated into distinct Pain, Vitality and Sleep domains in v1.8, and the psychometric properties examined. Methods A total of 131 consecutive SLE patients were self-administered surveys assessing fatigue (FACIT, SF-36), pain (Pain Inventory, SF-36), insomnia (Insomnia Severity Index), emotional health (PHQ-9, SF-36) and quality of life (SF-36, LupusPRO) at routine care visits. Internal consistency reliability (ICR) for each domain was obtained using Cronbach's alpha. The convergent construct validity of LupusPRO domains with corresponding SF-36 domains or tools were tested using Spearman correlation. Varimax rotations were conducted to assess factor structures of the LupusPRO v1.8. Results Mean (SD) age was 40.04 (14.10) years. Scores from the LupusPRO-Sleep domain strongly correlated with insomnia scores, while LupusPRO-Vitality correlated strongly with fatigue (FACIT) and SF-36 vitality. The LupusPRO-Pain domain correlated strongly with pain (SF36 Bodily-Pain, Pain Inventory) scores. Similarly, the LupusPRO domains of Physical and Emotional Health had significant correlations with corresponding SF-36 domains. The ICR for HRQoL and non-HRQoL were 0.96 and 0.81. LupusPRO (domains HRQoL and QoL) scores correlated with disease activity. Principal component analysis included seven factor loadings presenting for the HRQOL subscales (combined Sleep, Vitality, and Pain), and three factors for the NHRQoL (Combined Coping and Social Support). Conclusions LupusPRO v1.8 (including its Sleep, Vitality, and Pain domains) has acceptable reliability and validity. Use of LupusPRO as an outcome measure in clinical trials would facilitate responsiveness assessment.

[Lupus erythematosus panniculitis presenting as palpebral edema and parotiditis].

PubMed

Pérez-Pastor, G; Valcuende, F; Tomás, G; Moreno, M

2007-10-01

Lupus erythematosus panniculitis or lupus erythematosus profundus is characterized by inflammation of the deep dermis and subcutaneous tissue. It can occur in isolation or associated with chronic systemic or discoid lupus erythematosus. It usually consists of nodules and hardened subcutaneous plaques on the forehead, cheeks, proximal extremities, and buttocks. Periorbital and parotid involvement are rare and can lead to misdiagnosis. We present the case of a patient with lupus erythematosus panniculitis who presented with palpebral edema and involvement of the periocular fat and parotid gland.

Lupus mastitis as a first manifestation of systemic disease: About two cases with a review of the literature.

PubMed

Voizard, Béatrice; Lalonde, Lucie; Sanchez, Lilia Maria; Richard-Chesnay, Johanne; David, Julie; Labelle, Maude; El Khoury, Mona; Trop, Isabelle

2017-07-01

Lupus mastitis is an uncommon manifestation of systemic lupus erythematosus (SLE) that affects the subcutaneous fat in the breast, much like lupus panniculitis, but additionally involves the mammary gland. We report on two women for whom lupus mastitis was the initial manifestation of SLE and provide a literature review of 34 additional cases reported in the Anglo-Saxon and French literature since 1971, making this the largest review to date. Lupus mastitis (LM) can manifest clinically as subcutaneous masses that may be painful, or may present cutaneous involvement such as thickening and discolouration. The radiologic manifestations of LM are broad and include calcifications, masses and asymmetries. Most often, excluding malignancy requires percutaneous biopsy, with histologic findings that are virtually pathognomonic for SLE. Thus, surgery is avoided and medical management can begin, antimalarial drugs and corticosteroids in most cases. Copyright © 2017 Elsevier B.V. All rights reserved.

Antinuclear antibody panel

MedlinePlus

... ANA panel; ANA reflexive panel; SLE - ANA; Systemic lupus erythematosus - ANA ... have signs of an autoimmune disorder, particularly systemic lupus erythematosus . This test may be done if you ...

Evidence for gene-gene epistatic interactions among susceptibility loci for systemic lupus erythematosus.

PubMed

Hughes, Travis; Adler, Adam; Kelly, Jennifer A; Kaufman, Kenneth M; Williams, Adrienne H; Langefeld, Carl D; Brown, Elizabeth E; Alarcón, Graciela S; Kimberly, Robert P; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Boackle, Susan A; Stevens, Anne M; Reveille, John D; Sanchez, Elena; Martín, Javier; Niewold, Timothy B; Vilá, Luis M; Scofield, R Hal; Gilkeson, Gary S; Gaffney, Patrick M; Criswell, Lindsey A; Moser, Kathy L; Merrill, Joan T; Jacob, Chaim O; Tsao, Betty P; James, Judith A; Vyse, Timothy J; Alarcón-Riquelme, Marta E; Harley, John B; Richardson, Bruce C; Sawalha, Amr H

2012-02-01

Several confirmed genetic susceptibility loci for lupus have been described. To date, no clear evidence for genetic epistasis in lupus has been established. The aim of this study was to test for gene-gene interactions in a number of known lupus susceptibility loci. Eighteen single-nucleotide polymorphisms tagging independent and confirmed lupus susceptibility loci were genotyped in a set of 4,248 patients with lupus and 3,818 normal healthy control subjects of European descent. Epistasis was tested by a 2-step approach using both parametric and nonparametric methods. The false discovery rate (FDR) method was used to correct for multiple testing. We detected and confirmed gene-gene interactions between the HLA region and CTLA4, IRF5, and ITGAM and between PDCD1 and IL21 in patients with lupus. The most significant interaction detected by parametric analysis was between rs3131379 in the HLA region and rs231775 in CTLA4 (interaction odds ratio 1.19, Z = 3.95, P = 7.8 × 10(-5) [FDR ≤0.05], P for multifactor dimensionality reduction = 5.9 × 10(-45)). Importantly, our data suggest that in patients with lupus, the presence of the HLA lupus risk alleles in rs1270942 and rs3131379 increases the odds of also carrying the lupus risk allele in IRF5 (rs2070197) by 17% and 16%, respectively (P = 0.0028 and P = 0.0047, respectively). We provide evidence for gene-gene epistasis in systemic lupus erythematosus. These findings support a role for genetic interaction contributing to the complexity of lupus heritability. Copyright © 2012 by the American College of Rheumatology.

Racial and Ethnic Disparities in the Pregnancies of Women With Systemic Lupus Erythematosus.

PubMed

Clowse, Megan E B; Grotegut, Chad

2016-10-01

Both systemic lupus erythematosus (SLE; lupus) and pregnancy individually have significant racial disparities, with black women experiencing higher rates of complications, yet no large studies have focused on the impact of race/ethnicity on pregnancy outcomes among women with lupus. Using the Nationwide Inpatient Sample (NIS) for 2008-2010, pregnancy delivery discharges were identified and pregnancy outcomes were compared for women with lupus by maternal race/ethnicity. Adjusted odds ratios were used to compare pregnancy outcomes between black and white or Hispanic and white women with lupus. In this period, the NIS included 13,553 deliveries with lupus and 12,510,565 deliveries without lupus. Compared to white women with lupus, black and Hispanic women had higher rates of chronic hypertension, chronic renal failure, pneumonia, and acute renal failure. There was a high degree of pregnancy complication in all women with lupus, but especially in black and Hispanic women, with more than 40% cesarean-section delivery; preterm labor in 14.3% of white, 24.7% of black (odds ratio [OR] 1.97), and 20.6% of Hispanic (OR 1.56) deliveries; and preeclampsia and gestational hypertension in almost 20% of black and Hispanic pregnancies. After adjustment for predictors of pregnancy outcomes and racial differences in nonlupus pregnancy, black and Hispanic women with lupus had higher than expected rates of preeclampsia, preterm labor, and fetal growth restriction. Black and Hispanic women with lupus have disproportionately poor pregnancy outcomes. This study suggests that identifying the key causes of these differences and targeting interventions to the women of greatest need is an essential next step. © 2016, American College of Rheumatology.

Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus.

PubMed

Gómez-Guzmán, Manuel; Jiménez, Rosario; Romero, Miguel; Sánchez, Manuel; Zarzuelo, María José; Gómez-Morales, Mercedes; O'Valle, Francisco; López-Farré, Antonio José; Algieri, Francesca; Gálvez, Julio; Pérez-Vizcaino, Francisco; Sabio, José Mario; Duarte, Juan

2014-08-01

Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of cardiovascular disease, is present in lupus. Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. Vascular reactive oxygen species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47(phox) were increased in lupus mice and reduced by hydroxychloroquine or antioxidants. Chronic hydroxychloroquine treatment reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, despite the persistent elevation of anti-double-stranded DNA, suggesting the involvement of new additional mechanisms to improve cardiovascular complications. © 2014 American Heart Association, Inc.

Ethnic differences in DNA methyltransferases expression in patients with systemic lupus erythematosus.

PubMed

Wiley, Kenneth L; Treadwell, Edward; Manigaba, Kayihura; Word, Beverly; Lyn-Cook, Beverly D

2013-02-01

Systemic lupus erythematous (SLE) is a systemic autoimmune inflammatory disease with both genetic and epigenetic etiologies. Evidence suggests that deregulation of specific genes through epigenetic mechanisms may be a contributing factor to SLE pathology. There is increasing evidence that DNA methyltransferase activity may be involved. This study demonstrated modulation in expression of DNA methyltransferases (DNMTs) according to ethnicity in patients diagnosed with SLE. Furthermore, differential expression in one of the DNMTs was found in a subset of lupus patients on dehydroepiandrosterone (DHEA) therapy. Real-time PCR analyses of DNMT1, DNMT3A and DNMT3B in peripheral blood mononuclear cells from a cohort of African American and European American lupus and non-lupus women were conducted. Also, global DNA methylation was assessed using the MethylFlash(TM) methylated quantification colorimetric assay. Significant increase in DNMT3A (p < 0.001) was shown in lupus patients when compared to age-matched healthy controls. This increase was associated with a higher SLEDI index. More striking was that expression levels for African American (AA) women were higher than European American women in the lupus populations. A subset of AA women on DHEA therapy showed a significant decrease (p < 0.05) in DNMT3A expression in comparison to lupus patients not on the therapy. DHEA is an androgenic steroid found in low levels in the serum of lupus patients. Supplementation of this hormone has been shown to be beneficial to some lupus patients. DHEA was not shown to effect DNMT1 or DNMT3B expression. Increased expression was also noted in DNMT3B (p < 0.05) in lupus patients compared to age-matched healthy controls. However, no significant difference was noted in DNMT1 (p = 0.2148) expression between lupus patients and healthy controls. Although increases were detected in de novo methyltransferases, a global decrease (p < 0.001) in 5-methycytosine was observed in lupus patients when compared to age-matched healthy controls. These findings suggest that epigenetic changes may play a critical role in the manifestations of the disease observed among ethnic groups, particularly African American women who often have a higher incidence of lupus. DHEA therapy effects on DNMT3A expression in AA women warrant further investigation in a larger population.

Lenalidomide for refractory cutaneous manifestations of pediatric systemic lupus erythematosus.

PubMed

Wu, E Y; Schanberg, L E; Wershba, E C; Rabinovich, C E

2017-05-01

Objective Cutaneous manifestations of pediatric systemic lupus erythematosus cause significant morbidity. Lenalidomide, a thalidomide analogue, has shown promise treating cutaneous lupus erythematosus in adults. Our objective was to evaluate lenalidomide's efficacy and safety in treating refractory cutaneous manifestations of pediatric systemic lupus erythematosus. Methods We performed a retrospective chart review of 10 adolescents who received lenalidomide for recalcitrant cutaneous lupus erythematosus. Information was gathered at drug initiation and 6-month follow-up. The Wilcoxon matched-pairs signed-rank test was used to assess change in quantitative parameters of disease activity. Results Nine subjects were girls and six were African-American. Indications for lenalidomide treatment included alopecia, nasal and oral ulcers, extensive malar rash, discoid lesions, bullous lesions, panniculitis, cutaneous vasculitis, and Raynaud's phenomenon with digital ulcerations. Within 6 months, all patients demonstrated complete or near resolution based on physician report. Prednisone dose decreased from a mean 23.5 mg (SD± 13.3) to 12.25 mg (SD± 9.2) ( P= 0.008). Sedimentation rate decreased from a mean 29 mm/hour (SD± 31.5) to 17 mm/hour (SD± 18.1) ( P= 0.004). Lenalidomide was well tolerated. Conclusion Lenalidomide is an effective and safe treatment for a spectrum of dermatological conditions in pediatric systemic lupus erythematosus. Its use may allow a reduction in prednisone dose and decreased disfigurement. Prospective study is needed to clarify lenalidomide's role in treating cutaneous manifestations of systemic lupus erythematosus.

Anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus.

PubMed

Su, Fang; Xiao, Weiguo; Yang, Pingting; Chen, Qingyan; Sun, Xiaojie; Li, Tienan

2017-01-01

The clinical significance of anti-neutrophil cytoplasmic antibodies in patients with new-onset systemic lupus erythematosus, especially in systemic disease accompanied by interstitial lung disease remains to be elucidated. This study was designed to investigate the role of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients. A hundred and seven patients with new-onset SLE were enrolled. Presence of anti-neutrophil cytoplasmic antibodies in the sera was assessed by indirect immunofluorescence as well as enzyme linked immunosorbent assay against proteinase-3 and myeloperoxidase. Clinical features and laboratory parameters of patients were also recorded. All patients were subjected to chest X-ray, chest high-resolution computed tomography and pulmonary function test. Forty-five systemic lupus erythematosus patients (45/107, 42%) were seropositive for anti-neutrophil cytoplasmic antibodies. Compared with anti-neutrophil cytoplasmic antibodies-negative patients, the anti-neutrophil cytoplasmic antibodies-positive patients had significantly higher incidence of renal involvement, anemia, and Raynaud's phenomenon as well as decreased serum level of complement 3/complement 4 and elevated erythrocyte sedimentation rate. In addition, there was a positive correlation between serum anti-neutrophil cytoplasmic antibodies level and disease activity of systemic lupus erythematosus. Furthermore, prevalence of interstitial lung disease in the anti-neutrophil cytoplasmic antibodies -positive patients (25/45, 55.6%) was obviously higher than that in the anti-neutrophil cytoplasmic antibodies-negative patients (15/62, 24.2%). The sample size was limited and the criteria for screening new-onset systemic lupus erythematosus patients might produce bias. The level of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients correlates positively with the disease activity and the prevalence of interstitial lung disease.

Hypoparathyroidism associated with systemic lupus erythematosus.

PubMed

Gazarian, M; Laxer, R M; Kooh, S W; Silverman, E D

1995-11-01

We describe a 15-year-old girl with systemic lupus erythematosus (SLE) who presented with hypocalcemia and a generalized seizure in the setting of an intercurrent illness and active central nervous system lupus. She was subsequently found to have idiopathic hypoparathyroidism. The association of SLE with hypoparathyroidism is extremely rare and this case represents the first pediatric report of this rare association. We suggest there may be a common underlying pathophysiological process linking these diseases.

[Cardiac tamponade disclosing systemic lupus erythematosus].

PubMed

Nour-Eddine, M; Bennis, A; Soulami, S; Chraibi, N

1996-02-01

Cardiac tamponade secondary to systemic lupus erythematosus is rare and has a very serious prognosis. The authors report a case of cardiac tamponade confirmed by echocardiography, which constituted the presenting sign of systemic lupus erythematosus in a 20-year-old patient, who required emergency pericardial aspiration. The diagnosis of systemic lupus erythematosus was established on the basis of the combination of pericardial involvement, non-erosive arthritis, leukopenia with lymphopenia, presence of LE cells and anti-native DNA antibodies and positive antinuclear antibody titre of 1/2560. The clinical course was favourable in response to 3 months of corticosteroid treatment. The possibility of SLE should be considered in any case of cardiac tamponade in a young patient in which the aetiology is not explained.

Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma

DTIC Science & Technology

2015-10-01

first tested on a sera from healthy patients (n=20), systemic lupus erythematosus patients (n=29) and systemic sclerosis patients (n=20). Patients...with lupus and systemic sclerosis both had an increase in circulating soluble cadherin-11 levels that was statistically significant over levels seen...level. These data suggest that cadherin-11 levels are increased in patients with systemic sclerosis and lupus . These data use a small set of samples

Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma

DTIC Science & Technology

2016-05-01

first tested on a sera from healthy patients (n=20), systemic lupus erythematosus patients (n=29) and systemic sclerosis patients (n=20). Patients...with lupus and systemic sclerosis both had an increase in circulating soluble cadherin-11 levels that was statistically significant over levels seen...level. These data suggest that cadherin-11 levels are increased in patients with systemic sclerosis and lupus . These data use a small set of samples

SiLEncing SLE: the power and promise of small noncoding RNAs.

PubMed

Rigby, Robert J; Vinuesa, Carola G

2008-09-01

In this study, we outline the evidence suggesting that defects in the RNA silencing machinery can lead to the prototypic systemic autoimmune disease, systemic lupus erythematosus, and describe the potential for RNA interference to provide novel therapeutic agents. Over the last year, a class of small noncoding RNAs--microRNAs--have been shown to play key roles in immune regulation including T-cell selection in the thymus, B cell affinity maturation and selection in germinal centres, and development of regulatory T cells, suggesting that the microRNA machinery may be crucial in the maintenance of immunological tolerance. Two RNA silencing mechanisms have been shown to be involved in lupus pathogenesis: failed Roquin-mediated repression of inducible costimulatory receptors messenger RNA through miR-101 in roquin(san/san) mice and decreased expression of pro-apoptotic molecule and phosphatase and tensin homologue on chromosome 10 in mice transgenic for the miR-17-92 cluster, leading to lymphoproliferation and other lupus manisfestations. MicroRNA array experiments performed on peripheral blood mononuclear cells have revealed different expression profiles in systemic lupus erythematosus patients. RNA interference has also been used ex vivo to silence dysregulated T-cell molecules in cells from systemic lupus erythematosus patients. Dysregulation of the RNA silencing machinery has been implicated in systemic lupus erythematosus pathogenesis. Although microRNA profiling may prove to be a useful diagnostic and prognostic tool for a notoriously heterogeneous disease, manipulation of RNA interference emerges as a powerful and potentially specific means to correct dysregulated gene expression in systemic lupus erythematosus patients.

Coexistence of tumid lupus erythematosus with systemic lupus erythematosus and discoid lupus erythematosus: a report of two cases of tumid lupus.

PubMed

Stead, Jennifer; Headley, Catherine; Ioffreda, Michael; Kovarik, Carrie; Werth, Victoria

2008-12-01

Tumid lupus erythematosus (LE) is a rare variant of chronic cutaneous LE that is characterized clinically by smooth, nonscarring, pink to violaceous papules or plaques without evidence of surface change. Histopathologic features include superficial and deep lymphocytic infiltration in a perivascular and periadnexal distribution, with dermal interstitial mucin deposition and focal or absent dermoepidermal junction involvement. These clinical and histopathologic features can be challenging to differentiate from other cutaneous diseases. This is particularly true because patients with tumid LE usually do not have other manifestations of systemic LE or cutaneous LE. We present 2 cases of tumid LE, one associated with concomitant systemic LE and the other occurring concurrently with discoid LE. Furthermore, we demonstrate the rare occurrence of a patient with tumid LE occurring below the waist at a photo-protected site.

Treatment of Cutaneous Lupus Erythematosus

PubMed Central

Kim, Grace K.; Del Rosso, James Q.

2013-01-01

The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice. PMID:23320123

The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

PubMed

Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

2014-06-01

The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, p<0.001; 44.1 ± 46.8 ng/ml vs. 22.8 ± 3.0 ng/ml, p = 0.035, respectively). There was no significant difference of the serum connective tissue growth factor levels between non-renal systemic lupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, p<0.001) and acute renal failure (85.5 ± 75.0 ng/ml vs. 31.2 ± 21.8 ng/ml, p = 0.002). Serum connective tissue growth factor levels in class IV were significantly higher than that in class II, III and V (57.6 ± 57.5 ng/ml vs. 18.7 ± 6.4 ng/ml, p = 0.019; 57.6 ± 57.5 ng/ml vs. 25.2 ± 14.9 ng/ml, p = 0.006; 57.6 ± 57.5 ng/ml vs. 30.5 ± 21.3 ng/ml, p = 0.017, respectively). Serum connective tissue growth factor levels were significantly higher in those with both active/chronic lesions than those in those with active lesions only in either class IV (84.9 ± 69.6 ng/ml vs. 40.0 ± 40.2 ng/ml, p = 0.001) or in combination of class III and IV lupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, p<0.001) and positively associated with interstitial inflammation (r = 0.309, p = 0.002) and interstitial fibrosis (r = 0.287, p = 0.004). Serum connective tissue growth factor level was a risk factor for doubling of serum creatinine in lupus nephritis (p<0.001, hazard ratio = 1.015, 95% confidence intervals 1.008-1.022) in univariate analysis. Serum connective tissue growth factor levels were significantly higher in lupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The role of Epstein-Barr virus in systemic lupus erythematosus.

PubMed

McClain, M T; Harley, J B; James, J A

2001-10-01

Systemic lupus erythematosus (SLE) is a devastating autoimmune disease with no known cure. Lupus patients suffer from a myriad of clinical symptoms which variably include arthritis, pleuritis, pericarditis, vasculitis, and nephritis. The underlying mechanisms behind these clinical findings and the etiologic events preceding and causing disease onset, however, remain largely unknown. For many years, investigators have suspected that Epstein-Barr virus might somehow be involved in the etiology and/or pathogenesis of systemic lupus. Numerous studies have examined this possibility from various angles and have arrived at different conclusions. This work reviews these historical papers in the context of new results and presents a hypothetical role for this virus as an etiological environmental trigger for SLE.

Raynaud phenomenon

MedlinePlus

Raynaud's phenomenon; Sjögren syndrome - Raynaud; Rheumatoid arthritis - Raynaud; Systemic lupus erythematosus - Raynaud ... and autoimmune conditions (such as scleroderma , Sjögren syndrome , ... , and systemic lupus erythematosus ) Certain blood disorders, such ...

A Cutaneous Lupus Erythematosus-Like Eruption Induced by Hydroxyurea.

PubMed

Yanes, Daniel A; Mosser-Goldfarb, Joy L

2017-01-01

Hydroxyurea is a medication with many well-described cutaneous side effects, notably the dermatomyositis-like eruption known as hydroxyurea dermopathy. Although systemic lupus erythematosus has been reported with hydroxyurea use, cutaneous lupus has not. We report a novel case of chronic cutaneous lupus induced by hydroxyurea and propose that this is a side effect that is distinct from hydroxyurea dermopathy. © 2016 Wiley Periodicals, Inc.

Invasive fungal infections in Colombian patients with systemic lupus erythematosus.

PubMed

Santamaría-Alza, Y; Sánchez-Bautista, J; Fajardo-Rivero, J F; Figueroa, C L

2018-06-01

Introduction Systemic lupus erythematosus is an autoimmune disease with multi-organ involvement. Complications, such as invasive fungal infections usually occur in patients with a greater severity of the disease. Objective The objective of this study was to determine the prevalence and risk variables associated with invasive fungal infections in a Colombian systemic lupus erythematosus population. Materials and methods A cross-sectional, retrospective study that evaluated patients with systemic lupus erythematosus for six years. The primary outcome was invasive fungal infection. Descriptive, group comparison and bivariate analysis was performed using Stata 12.0 software. Results Two hundred patients were included in this study; 84.5% of the patients were women and the median age was 36 years; 68% of the subjects had haematological complications; 53.3% had nephropathy; 45% had pneumopathy and 28% had pericardial impairment; 7.5% of patients had invasive fungal infections and the most frequently isolated fungus was Candida albicans. Pericardial disease, cyclophosphamide use, high disease activity, elevated ESR, C3 hypocomplementemia, anaemia and lymphopenia had a significant association with invasive fungal infection ( P < 0.05). Conclusions We describe for the first time the prevalence of invasive fungal infection in a Colombian population with systemic lupus erythematosus, which was higher than that reported in other latitudes. In this population the increase in disease activity, the presence of pericardial impairment and laboratory alterations (anaemia, lymphopenia, increased ESR and C3 hypocomplementemia) are associated with a greater possibility of invasive fungal infections. Regarding the use of drugs, unlike other studies, in the Colombian population an association was found only with the previous administration of cyclophosphamide. In addition, patients with invasive fungal infections and systemic lupus erythematosus had a higher prevalence of mortality and hospital readmission compared with patients with systemic lupus erythematosus without invasive fungal infection.

Novel Therapeutic Target for the Treatment of Lupus

DTIC Science & Technology

2013-08-01

RhoB, animal model, antibody secretion, antibody therapy, Systemic lupus erythematosus , autoantibodies. 16. SECURITY CLASSIFICATION OF: 17...6 References………………………………………………………………………………..6 Appendices………………………………………………………………………………..N/A 4 INTRODUCTION: Systemic lupus ...Treatment of Lupus PRINCIPAL INVESTIGATOR: Lisa Laury-Kleintop, Ph.D. Laura Mandik-Nayak, Ph.D

Mucormycosis complications in systemic lupus erythematosus.

PubMed

Arce-Salinas, C A; Pérez-Silva, E

2010-07-01

This case involved a 75-year-old woman with systemic lupus erythematosus. Two months previously, she had a flare that was treated successfully by increasing the dosages of prednisone and azathioprine. A sudden onset of ocular pain, diplopia, and loss of vision suggestive of optical neuritis or vascular involvement confused the issue, and rhinocerebral zygomycosis was demonstrated later. We review the presentations of this fungal infection in patients with systemic lupus erythematosus with emphasis on its initial features.

Cutaneous lupus erythematosus of elbows: A distinct entity?

PubMed

Singh, Nidhi; Chandrashekar, Laxmisha; Kumar, Nava; Kar, Rakhee; Sylvia, Mary Theresa; Thappa, Devinder Mohan

2016-01-01

The elbow is not recognized as common site for cutaneous lupus erythematosus (CLE) lesions. Twelve cases of CLE over the elbows were evaluated for systemic involvement and Cutaneous Lupus Disease Area and Severity Index activity and damage scores and Systemic Lupus Erythematosus Disease Activity Index scoring was done. Histopathological examination of the affected skin was performed in doubtful cases. Most of the patients were women (10, 83.3%) with mean age of 28.75 years. Three patients had only elbow lesions and the remaining nine patients had CLE lesions at sites other than the elbows, of which five had elbow lesions preceding skin lesions elsewhere over the body and three patients were not aware of whether elbow lesions preceded or succeeded CLE lesions at other sites, and one patient had noticed malar rash 9 months prior to elbow lesions. All the patients antinuclear antibody positivity, systemic involvement, and fulfilled criteria for systemic lupus erythematosus. This peculiar localization of CLE to the elbows may be associated with a greater risk of systemic involvement and may be an predictor of flare of LE.

Bilateral sudden sensorineural hearing loss as a presenting feature of systemic lupus erythematosus

PubMed Central

Chawki, Sylvain; Aouizerate, Jessie; Trad, Selim; Prinseau, Jacques; Hanslik, Thomas

2016-01-01

Abstract Introduction: Sudden sensorineural hearing loss is an unusual presenting clinical feature of systemic lupus erythematosus. Case report: We report the case of a young woman who was admitted to hospital for sudden sensorineural hearing loss and hemophagocytic syndrome which was attributed to systemic lupus erythematosus on the basis of specific renal involvement, thrombocytopenia, and consistent autoantibodies. Favorable outcome was obtained on high-dose corticosteroids, and the hearing fully recovered. Discussion: Sudden sensorineural hearing loss in systemic lupus erythematosus is seemingly more frequently associated with severe systemic involvement and antiphospholipid antibodies may be present. Although management remains empirical, the high risk of permanent hearing impairment seems to justify emergency treatment with high-dose corticosteroids. When the clinical and laboratory criteria of antiphospholipid syndrome are met, antiplatelets agents or anticoagulation therapy shall be considered. PMID:27603334

Neuropsychiatric lupus erythematosus, cerebral infarctions, and anticardiolipin antibodies.

PubMed Central

Fields, R A; Sibbitt, W L; Toubbeh, H; Bankhurst, A D

1990-01-01

Anticardiolipin antibody (aCL) has been associated with thromboembolic phenomena, including stroke, in certain patients with systemic lupus erythematosus (SLE); however, the relation between this antibody and the central nervous system manifestations of SLE is unknown. Serum samples and cerebrospinal fluid from five patients with SLE and acute central nervous system manifestations were assayed for the presence of aCL. Anticardiolipin antibody was identified in sera from four of the five patients but in none of the cerebrospinal fluid samples. Nuclear magnetic resonance imaging showed 'infarct-like' lesions in these four patients. This preliminary study suggests that a correlation between serum aCL and cerebral infarcts in central nervous system lupus may potentially exist. From this limited study it seems unlikely that aCL has a direct pathogenic role in the diffuse encephalopathy of acute central nervous system lupus. Images PMID:2317112

Recent advances in cytokines in cutaneous and systemic lupus erythematosus.

PubMed

Mikita, Naoya; Ikeda, Takaharu; Ishiguro, Mariko; Furukawa, Fukumi

2011-09-01

Lupus erythematosus (LE) includes a broad spectrum of diseases from a cutaneous-limited type to a systemic type. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which affects multiple organs. Cutaneous lupus erythematosus (CLE) includes skin symptoms seen in SLE and cutaneous-limited LE. Although immune abnormalities, as well as heritable, hormonal and environmental factors, are involved in the pathology of LE, the actual pathogenesis is still unclear. Recently, the involvement of various cytokines has been shown in the pathogenesis of LE. Moreover, some trials with biological agents targeted specific cytokines are also ongoing for SLE. In this article, we review the contributions of major cytokines such as interferon, tumor necrosis factor-α and interleukin-18 to LE, especially SLE and CLE. © 2011 Japanese Dermatological Association.

A Randomized, Double-blind, Placebo-controlled Clinical Trial Examining the Effects of Green Tea Extract on Systemic Lupus Erythematosus Disease Activity and Quality of Life.

PubMed

Shamekhi, Z; Amani, R; Habibagahi, Z; Namjoyan, F; Ghadiri, Ata; Saki Malehi, A

2017-07-01

Antiinflammatory and immunomodulatory benefit of green tea (Camellia sinensis) in autoimmune disease has been proven in recent studies. The objective of this study was to assess the effects of green tea on disease activity and quality of life in systemic lupus erythematosus patients. A randomized controlled trial on subjects with lupus was conducted, and 68 patients in the age range of 39.1 ± 10.3 years and body mass index of 25.7 ± 5.21 kg/m 2 completed the 12-week study. Patients were randomly divided into two groups of intervention (1000 mg green tea extract, two capsules/day) and control (1000 mg of starch, two capsules/day). Main outcome measure, systemic lupus erythematosus disease activity, was assessed by the systemic lupus erythematosus disease activity index at the first and after 3 months of intervention. In addition, patient's quality of life was evaluated by short form of quality-of-life questionnaire at baseline and after 3 months. Green tea extract supplementation significantly reduced disease activity in lupus patients (p < 0.004); in addition, it significantly increased the vitality (p < 0.006) and general health (p < 0.01). This study showed that daily consumption of green tea extracts for 12 weeks improves the systemic lupus erythematosus disease activity as well as some aspects of quality of life. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Prognostic implications of active discoid lupus erythematosus and malar rash at the time of diagnosis of systemic lupus erythematosus: Results from a prospective cohort study.

PubMed

Drucker, A M; Su, J; Mussani, F; Siddha, S K; Gladman, D D; Urowitz, M B

2016-04-01

Cutaneous lupus erythematosus (CLE) may have prognostic implications for systemic lupus erythematosus (SLE). We aimed to determine the impact of discoid lupus erythematosus (DLE) and malar rash on SLE disease activity. Data were analyzed from the Toronto Lupus Clinic prospective cohort study. We compared SLE patients with active DLE or malar rash at SLE diagnosis to SLE patients who never developed CLE. Outcomes were assessed at one and five years, including Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (AMS). A total of 524 SLE patients (284 without CLE, 65 with DLE, and 175 with malar rash) were included. Mean AMS scores in patients without CLE at one and five years were 5.96 ± 5.06 and 4.00 ± 3.52, which did not differ significantly from scores at one (6.93 ± 5.31, p = 0.17) and five years (4.29 ± 2.62, p = 0.63) in the DLE group. In patients with malar rash, AMS scores at one (8.30 ± 6.80, p < 0.001) and five years (5.23 ± 3.06, p = 0.004) were higher than controls without CLE. Malar rash may be a marker of more severe systemic disease over time, while DLE has no significant impact on general SLE disease activity. © The Author(s) 2015.

Persistent periorbital edema as a sole manifestation of cutaneous lupus erythematosus: report of two cases.

PubMed

Ghaninejad, H; Kavusi, S; Safar, F; Asgari, M; Naraghi, Z S

2006-02-28

In lupus erythematosus, dramatic periorbital edema and erythema without any evidence of other significant cutaneous or systemic involvement is unusual. We describe two patients with severe periorbital edema and erythema as the sole manifestation of cutaneous lupus erythematosus.

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.

PubMed

Patel, Zubin; Lu, Xiaoming; Miller, Daniel; Forney, Carmy R; Lee, Joshua; Lynch, Arthur; Schroeder, Connor; Parks, Lois; Magnusen, Albert F; Chen, Xiaoting; Pujato, Mario; Maddox, Avery; Zoller, Erin E; Namjou, Bahram; Brunner, Hermine I; Henrickson, Michael; Huggins, Jennifer L; Williams, Adrienne H; Ziegler, Julie T; Comeau, Mary E; Marion, Miranda C; Glenn, Stuart B; Adler, Adam; Shen, Nan; Nath, Swapan K; Stevens, Anne M; Freedman, Barry I; Pons-Estel, Bernardo A; Tsao, Betty P; Jacob, Chaim O; Kamen, Diane L; Brown, Elizabeth E; Gilkeson, Gary S; Alarcón, Graciela S; Martin, Javier; Reveille, John D; Anaya, Juan-Manuel; James, Judith A; Sivils, Kathy L; Criswell, Lindsey A; Vilá, Luis M; Petri, Michelle; Scofield, R Hal; Kimberly, Robert P; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Bang, So-Young; Lee, Hye-Soon; Bae, Sang-Cheol; Boackle, Susan A; Cunninghame Graham, Deborah; Vyse, Timothy J; Merrill, Joan T; Niewold, Timothy B; Ainsworth, Hannah C; Silverman, Earl D; Weisman, Michael H; Wallace, Daniel J; Raj, Prithvi; Guthridge, Joel M; Gaffney, Patrick M; Kelly, Jennifer A; Alarcón-Riquelme, Marta E; Langefeld, Carl D; Wakeland, Edward K; Kaufman, Kenneth M; Weirauch, Matthew T; Harley, John B; Kottyan, Leah C

2018-04-18

Systemic Lupus Erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly-replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared to the non-risk allele of rs11889341. We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1.

Leptin levels in patients with systemic lupus erythematosus inversely correlate with regulatory T cell frequency.

PubMed

Wang, X; Qiao, Y; Yang, L; Song, S; Han, Y; Tian, Y; Ding, M; Jin, H; Shao, F; Liu, A

2017-11-01

Leptin levels are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity. Importantly, increased leptin in lupus patients inversely correlated with the frequency of Tregs but not in controls, and leptin neutralization resulted in the expansion of Tregs ex vivo. Thus, hyperleptinemia in lupus patients correlates directly with disease activity and inversely with Treg frequency. The finding that leptin inhibition expands Tregs in SLE suggests possible inhibition of this molecule for an enhanced Treg function in the disease.

Papulonodular mucinosis, Guillain-Barré syndrome and nephrotic syndrome in a patient with systemic lupus erythematosus: a case report.

PubMed

Su, Xiaole; Qiao, Xi; Li, Jing; Gao, Lifang; Wang, Chen; Wang, Lihua

2017-02-01

Awareness of the spectrum of clinical manifestations of systemic lupus erythematosus (SLE), especially uncommon changes, is essential for diagnosis and effective management of patients. A 26-year-old Chinese man with SLE initially manifested cutaneous papulonodular mucinosis and developed acute Guillain-Barré syndrome and class V lupus nephritis 2 years later. His cutaneous nodules had not been idententified for 2 years and were resected by surgical procedures twice until SLE was diagnosed. The kidney biopsy revealed class V lupus nephritis. The patient responded well to a short course of intravenous immunoglobulins and his muscle strength almost completely recovered. So far, he has undergone five cycles of cyclophosphamide combined with hydroxychloroquine and tapering prednisone, resulting in partial remission of lupus nephritis and disappearance of hypocomplementemia. We reported a rare case of male patient with SLE with manifestation of class V lupus nephritis, Guillain-Barré syndrome and papulonodular mucinosis.

Pyomyositis in childhood-systemic lupus erythematosus.

PubMed

Blay, Gabriela; Ferriani, Mariana P L; Buscatti, Izabel M; França, Camila M P; Campos, Lucia M A; Silva, Clovis A

2016-01-01

Pyomyositis is a pyogenic infection of skeletal muscle that arises from hematogenous spread and usually presents with localized abscess. This muscle infection has been rarely reported in adult-onset systemic lupus erythematous and, to the best of our knowledge, has not been diagnosed in pediatric lupus population. Among our childhood-onset systemic lupus erythematous population, including 289 patients, one presented pyomyositis. This patient was diagnosed with childhood-onset systemic lupus erythematous at the age of 10 years-old. After six years, while being treated with prednisone, azathioprine and hydroxychloroquine, she was hospitalized due to a 30-day history of insidious pain in the left thigh and no apparent trauma or fever were reported. Her physical examination showed muscle tenderness and woody induration. Laboratory tests revealed anemia, increased acute phase reactants and normal muscle enzymes. Computer tomography of the left thigh showed collection on the middle third of the vastus intermedius, suggesting purulent stage of pyomyositis. Treatment with broad-spectrum antibiotic was initiated, leading to a complete clinical resolution. In conclusion, we described the first case of pyomyositis during childhood in pediatric lupus population. This report reinforces that the presence of localized muscle pain in immunocompromised patients, even without elevation of muscle enzymes, should raise the suspicion of pyomyositis. A prompt antibiotic therapy is strongly recommended. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Total lymphoid irradiation in refractory systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ben-Chetrit, E.; Gross, D.J.; Braverman, A.

1986-07-01

In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation inmore » patients with severe systemic lupus erythematosus should be regarded as strictly experimental.« less

Atypical presentation of systemic lupus erythematosus: parotitis and secondary Sjogren's syndrome. Case report.

PubMed

Criscov, Geanina Irina; Rugină, Aurica; Stana, A B; Azoicăi, Alice Nicoleta; Moraru, Eovelina

2014-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by auto antibodies directed against self-antigens, immune complex formation and immune deregulations and may affect joints, skin, kidneys, heart, lungs, nervous system, and immune system. The onset can be variable and the symptoms can occur for many years. Parotitis as the initial manifestation of systemic lupus erythematosus (SLE) is a rare condition and can be associated with Sjogren's syndrome. In this article we present the case of a young patient who was diagnosed with Sjogren's syndrome retrospectively, after she met the criteria for SLE.

21 CFR 866.5320 - Properdin factor B immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of the glomeruli of the kidney), lupus nephritis (kidney disease associated with a multisystem autoimmune disease, systemic lupus erythematosus), as well as several skin diseases, e.g., dermititis...

Metabolic Factors that Contribute to Lupus Pathogenesis

PubMed Central

Li, Wei; Sivakumar, Ramya; Titov, Anton A.; Choi, Seung-Chul; Morel, Laurence

2017-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease in which organ damage is mediated by pathogenic autoantibodies directed against nucleic acids and protein complexes. Studies in SLE patients and in mouse models of lupus have implicated virtually every cell type in the immune system in the induction or amplification of the autoimmune response as well as the promotion of an inflammatory environment that aggravates tissue injury. Here, we review the contribution of CD4+ T cells, B cells, and myeloid cells to lupus pathogenesis and then discuss alterations in the metabolism of these cells that may contribute to disease, given the recent advances in the field of immunometabolism. PMID:27480903

Role of MHC-Linked Susceptibility Genes in the Pathogenesis of Human and Murine Lupus

PubMed Central

Relle, Manfred; Schwarting, Andreas

2012-01-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies against nuclear antigens and a systemic inflammation that can damage a broad spectrum of organs. SLE patients suffer from a wide variety of symptoms, which can affect virtually almost any tissue. As lupus is difficult to diagnose, the worldwide prevalence of SLE can only be roughly estimated to range from 10 and 200 cases per 100,000 individuals with dramatic differences depending on gender, ethnicity, and location. Although the treatment of this disease has been significantly ameliorated by new therapies, improved conventional drug therapy options, and a trained expert eye, the underlying pathogenesis of lupus still remain widely unknown. The complex etiology reflects the complex genetic background of the disease, which is also not well understood yet. However, in the past few years advances in lupus genetics have been made, notably with the publication of genome-wide association studies (GWAS) in humans and the identification of susceptibility genes and loci in mice. This paper reviews the role of MHC-linked susceptibility genes in the pathogenesis of systemic lupus erythematosus. PMID:22761632

Hypogonadism and the risk of rheumatic autoimmune disease

PubMed Central

Snih, Soham Al; Raji, Mukaila A.; Urban, Randall J.; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S.; Baillargeon, Gwen; Kuo, Yong-Fang

2017-01-01

Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation’s largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms. PMID:27325124

Hypogonadism and the risk of rheumatic autoimmune disease.

PubMed

Baillargeon, Jacques; Al Snih, Soham; Raji, Mukaila A; Urban, Randall J; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S; Baillargeon, Gwen; Kuo, Yong-Fang

2016-12-01

Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation's largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms.

Novel Therapeutic Target for the Treatment of Lupus

DTIC Science & Technology

2014-09-01

AWARD NUMBER: W81XWH-12-1-0205 TITLE: Novel Therapeutic Target for the Treatment of Lupus PRINCIPAL INVESTIGATOR: Lisa Laury-Kleintop...SUBTITLE 5a. CONTRACT NUMBER Novel Therapeutic Target for the Treatment of Lupus 5b. GRANT NUMBER W81XWH-12-1-0205 5c. PROGRAM ELEMENT NUMBER 6...Systemic lupus erythematosus, autoantibodies. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 7 19a. NAME OF

Epstein-Barr virus infection induces lupus autoimmunity.

PubMed

Harley, John B; James, Judith A

2006-01-01

Systemic lupus erythematosus (SLE or lupus) is a systemic autoimmune disease characterized by a constellation of varied clinical presentations, although the nearly universal presence of autoantibodies is a salient unifying feature. Ongoing research efforts focus on understanding the complex combination of genetic and environmental factors that lead to SLE in select individuals. Our previous work has demonstrated that years before diagnosis abnormal autoantibody responses are present in the sera of patients who will subsequently develop lupus and, further, that the initial targets of two of these key responses (anti-Sm B' and anti-60 kD Ro alone) have been identified for some patients. Indeed, our results suggest that the first lupus-specific autoantibodies arise from particular antibodies directed against Epstein-Barr virus Nuclear Antigen-1 (EBNA-1) and that infection with Epstein-Barr virus (EBV) is an environmental risk factor for lupus. The predicted sequence of events is normal immunity, followed by Epstein- Barr virus infection, the generation of anti-EBNA-1 antibodies, then followed by those particular anti-EBNA-1 antibodies that also bind lupus-specific autoantigens (Sm or Ro), followed by the development of more complex autoimmune responses, and, finally, culminating in clinical disease. Studies from others and those underway suggest that lupus patients have unusual immune responses to Epstein-Barr virus. In aggregate, these results are consistent with an immune response against Epstein-Barr virus being important in at least some patients for the initiation of lupus autoimmunity.

Lupus erythematosus (LE) cells in ascites: initial diagnosis of systemic lupus erythematosus by cytological examination: a case report.

PubMed

Chou, Kun-Ta; Lee, Yu-Chin; Chen, Chun-Wei; Shih, Jen-Fu; Tung, Su-Mei; Yang, Ya-Ting; Perng, Reury-Perng

2007-11-01

Systemic lupus erythematosus (SLE) is an autoimmune disease, involving multiple organs. Diverse manifestations may obscure the diagnosis and confuse our thinking process, especially when few clues are present at the beginning. Serositis is one of the various presentations, and the presence of lupus erythematosus (LE) cell in body fluid may be a hint for the final diagnosis of SLE. Herein, we present a young female patient diagnosed of SLE with initial presentation of lupus peritonitis. Finding of LE cell in ascites prompted us for immunologic survey. Diagnosis of SLE was confirmed with high titer of anti-nuclear antibody and antibody to double-stranded DNA. Cytologic examination of body fluid is mainly useful in detecting malignant cells, but high specificity of this marker aids in early diagnosis of SLE.

[Lupus nephropathy in black patients with systemic lupus erythematosus in Senegal: 43 cases].

PubMed

Ka, E F; Cisse, M M; Lemrabott, A T; Fall, S; Diallo, M; Diallo, S; Faye, M; Niang, A; Diouf, B

2013-01-01

This study sought to assess the prevalence of lupus nephropathy and to determine its clinical, histological, therapeutic and outcome profiles. This retrospective study examined records covering a 10-year period from 1999 to 2009 at the nephrology department of the Aristide Le Dantec University Hospital Center. The records showed 43 patients with systemic lupus erythematosus (SLE), and 72% had lupus nephritis. The patients' mean age was 32.9 years; 40 were women and 3 men, for a sex ratio of 0.075. The lupus nephritis led to discovery of SLE in 27.9%. The mean proteinuria concentration was 2.01 g/dL. Seventeen patients had impaired renal function, and 26 had renal biopsies. It found class II nephritis in 2 patients, class IV in 10, and class V in 12. In addition, fifteen patients received combined corticosteroid + immunosuppressant treatment. Four patients died during the study period, one from SLE activity, two from complications of renal failure, and the fourth from sepsis. A larger study would be useful to assess more acurately the prevalence of various classes and severity of lupus nephropathy among blacks living in sub-Saharan Africa.

Immunometabolism in systemic lupus erythematosus.

PubMed

Morel, Laurence

2017-05-01

Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes. Beyond the activation of autoreactive B cells, this process involves dysregulation in many other types of immune cells, including CD4 + T cells, dendritic cells, macrophages and neutrophils. Metabolic substrate utilization and integration of cues from energy sensors are critical checkpoints of effector functions in the immune system, with common as well as cell-specific programmes. Patients with SLE and lupus-prone mice present with activated metabolism of CD4 + T cells, and the use of metabolic inhibitors to normalize these features is associated with therapeutic effects. Far less is known about the metabolic requirements of B cells and myeloid cells in SLE. This article reviews current knowledge of the alterations in metabolism of immune cells in patients with SLE and mouse models of lupus in the context of what is known about the metabolic regulation of these cells during normal immune responses. How these alterations might contribute to lupus pathogenesis and how they can be targeted therapeutically are also discussed.

Management of cardiovascular risk in systemic lupus erythematosus: a systematic review.

PubMed

Andrades, C; Fuego, C; Manrique-Arija, S; Fernández-Nebro, A

2017-11-01

Systemic lupus erythematosus is associated with accelerated atherosclerosis and increased risk of cardiovascular complications. The aim of this study was to review the effectiveness of interventions for primary and secondary prevention of cardiovascular events and mortality and to review the effectiveness of interventions for cardiovascular risk factor reduction in systemic lupus erythematosus patients. A systematic review was conducted. Electronic databases Medline and Embase (1961-2015) were searched. Nineteen articles met the inclusion criteria and were selected. Low-calorie and/or low glycaemic index calories may be a useful option for secondary prevention in obese patients with systemic lupus erythematosus, and exercise would be useful in improving the endothelial function measured by flow-mediated dilation in this group of patients. The use of lipid-lowering drugs may improve the lipid profile in patients with systemic lupus erythematosus and hyperlipidaemia, but the effect of this treatment on overall cardiovascular mortality remains unknown. Antiplatelets, anticoagulants, antimalarials and lipid-lowering drugs may be effective in the primary and secondary prevention of major cardiovascular events, such as acute myocardial infarction or stroke. Similarly, lipid-lowering drugs and antimalarial drugs appear to reduce the serum levels of total cholesterol, low-density lipoprotein, glucose, diastolic blood pressure and calcium deposition at the coronary arteries. They may also improve insulin resistance and the level of high-density lipoproteins. It appears that treatment with antihypertensive drugs reduces blood pressure in patients with systemic lupus erythematosus, but the available studies are of low quality.

N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus

PubMed Central

Liao, Tang-Dong; Nakagawa, Pablo; Janic, Branislava; D'Ambrosio, Martin; Worou, Morel E.; Peterson, Edward L.; Rhaleb, Nour-Eddine; Yang, Xiao-Ping

2015-01-01

Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis, and end-organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e., Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis, Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 wk had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5, and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP-treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1, and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system. PMID:25740596

Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells

PubMed Central

Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

2014-01-01

Blood–brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0·05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings. PMID:24801999

Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells.

PubMed

Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

2014-11-01

Blood-brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0 · 05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings. © 2014 John Wiley & Sons Ltd.

Systemic lupus erythematosus presenting as morbid jealousy.

PubMed Central

Ravindran, A.; Carney, M. W.; Denman, A. M.

1980-01-01

A patient fulfilling the diagnostic criteria for systemic lupus erythematosus and presenting with morbid jealousy is described. There was evidence of cerebral lupus. Her physical and mental symptoms responded to a combination of chlorpromazine and steroids. The morbid mental process was probably caused by her physical condition while the content of her disordered thought and behaviour was determined by her introverted premorbid personality, religiosity, unhappy childhood experiences and frustrated desire for children. PMID:7413541

Papulonodular mucinosis in a suspected systemic lupus erythematosus patient.

PubMed

Ausavarungnirun, Rujikan; Srisuttiyakorn, Chutika

2014-02-01

We present a 45-years-old suspected systemic lupus erythematosus (SLE) woman who had papulonodular mucinosis (PNM), without other cutaneous LE lesion. The lesions of PNM distributed on both legs which were an unusual location. In addition, the renal involvement was found and suspected from lupus nephritis. The patient was treated with prednisolone, mycofenolate mofetil and chloroquine. After 2 months of follow-up, the renal involvement was improved along with the disappearance ofskin lesions.

Burden of lupus on work: Issues in the employment of individuals with lupus.

PubMed

Agarwal, Neelam; Kumar, Vinod

2016-10-17

Systemic lupus erythematosus (SLE) or Lupus is one of the leading causes of work disability in the United States, accounting for about 20% of the more than estimated 1.5 million Americans with a work disability. The symptoms of lupus can have a profound impact on the person's employment. Impacts of lupus are more pronounced among young and middle-adulthood. Studies have shown that loss in work hours cost the nation nearly $13 billion annually. The loss also impacts the individual's work, quality of life, self-management, and self-efficacy. In this article, the author describes the financial burden of lupus. The article also describes the substantial impact of lupus on employment outcomes for individuals living with the condition. The author also reviews major signs and symptoms of disease and their impact on employment. Findings from this research can be used to identify various accommodations and strategies for individuals to prevent flare-ups. The paper presents innovative strategies that include early interventions and how employers andco-workers can provide helpful support that includes job accommodations to individuals with lupus.

The involvement of galectin-3 in skin injury in systemic lupus erythematosus patients.

PubMed

Shi, Z; Meng, Z; Han, Y; Cao, C; Tan, G; Wang, L

2018-04-01

Objective Our previous research suggested that anti-galectin-3 antibody was highly associated with the development of lupus skin lesions in systemic lupus erythematosus (SLE). In this study we aimed to investigate the involvement of galectin-3 in SLE skin damage. Methods The study consisted of 49 patients with SLE, 16 with dermatomyositis and 11 with systemic scleroderma and 20 healthy controls. Galectin-3 was examined by ELISA and immunohistochemical staining in serum and skin, respectively. Results Serum galectin-3 was significantly higher in patients with SLE than in those with dermatomyositis ( P < 0.01), systemic scleroderma ( P < 0.001) and healthy controls ( P < 0.001); however, it was comparable between SLE patients with and without skin lesions ( P = 0.2010 and was not correlated with cutaneous disease activity ( r = -0.020, P = 0.93) or damage score ( r = -0.380, P = 0.09). Galectin-3 expression was reduced in epidermis in lesional skin from patients with SLE, dermatomyositis and systemic scleroderma compared to healthy controls ( P = 0.0055), whereas it was comparable among diseases ( P > 0.05). As for subtypes of skin lesions in SLE, galectin-3 expression was lower in chronic cutaneous lupus erythematosus than in acute cutaneous lupus erythematosus ( P = 0.0439). Conclusion Serum galectin-3 is unlikely to play a role in the pathogenesis of lupus skin damage, but can be a potential biomarker for the measurement of SLE disease activity. Galectin-3 is greatly reduced in patients with lupus lesions compared with healthy controls, which may contribute to the recruitment of inflammatory cells in the skin.

Correlation between the Modified Systemic Lupus Erythematosus Disease Activity Index 2000 and the European Consensus Lupus Activity Measurement in juvenile systemic lupus erythematosus.

PubMed

Sato, J O; Corrente, J E; Saad-Magalhães, C

2016-11-01

Objective The objective of this study was to assess Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and European Consensus Lupus Activity Measurement (ECLAM) disease activity correlation in addition to their respective correlation to Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI), in juvenile systemic lupus erythematosus (JSLE). Methods The activity indices were scored retrospectively and summarized by adjusted means during follow-up. The Ped-SDI was scored during the last visit for those with more than six months follow-up. Pearson correlation between the Modified SLEDAI-2K and ECLAM, as well as Spearman correlations between the Modified SLEDAI-2K, ECLAM, and Ped-SDI were calculated. The receiver operating characteristic (ROC) curve was calculated for both activity indices discriminating damage measured by Ped-SDI. Results Thirty-seven patients with mean age at diagnosis 11 ± 2.9 years and mean follow-up time 3.2 ± 2.4 years were studied. The Modified SLEDAI-2K and ECLAM adjusted means were highly correlated ( r = 0.78, p < 0.001). Similarly, Spearman correlation between the activity indices was also high ( r s  > 0.7, p < 0.001), but Modified SLEDAI-2K and ECLAM correlation with Ped-SDI was only moderate. ROC analysis discriminant performance for both activity indices resulted in area under curve (AUC) of 0.74 and 0.73 for Modified SLEDAI-2K and ECLAM, respectively. Conclusion The high correlation found between the Modified SLEDAI-2K and ECLAM adjusted means indicated that both tools can be equally useful for longitudinal estimates of JSLE activity.

Effective Self-Management Interventions for Patients With Lupus: Potential Impact of Peer Mentoring.

PubMed

Williams, Edith M; Egede, Leonard; Faith, Trevor; Oates, James

2017-06-01

Systemic lupus erythematosus (SLE) is associated with significant mortality, morbidity and cost for the individual patient and society. In the United States, African Americans (AAs) have 3-4 times greater prevalence of lupus, risk of developing lupus at an earlier age and lupus-related disease activity, organ damage and mortality compared with whites. Evidence-based self-management interventions that incorporate both social support and health education have reduced pain, improved function and delayed disability among patients with lupus. However, AAs and women are still disproportionately affected by lupus. This article presents the argument that peer mentoring may be an especially effective intervention approach for AA women with SLE. SLE peers with a track record of success in lupus management and have a personal perspective that clinicians often lack. This commonality and credibility can establish trust, increase communication and, in turn, decrease disparities in healthcare outcomes. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Characteristics of pleural effusions in systemic lupus erythematosus: differential diagnosis of lupus pleuritis.

PubMed

Choi, B Y; Yoon, M J; Shin, K; Lee, Y J; Song, Y W

2015-03-01

We investigated the clinical characteristics of pleural effusion in systemic lupus erythematosus (SLE). A prospective analysis of 17 SLE patients with pleural effusion (seven lupus pleuritis, eight transudative effusions and two parapneumonic effusions) was performed. Thirty non-SLE patients with pleural effusion were recruited as controls. A pleural fluid ANA titer ≥1:160 was found in 8/17 (47.1%) SLE patients and none of the 30 non-SLE patients (p = 0.0001). Pleural fluid to serum C3 ratios were significantly lower in SLE than in non-SLE (median (minimum-maximum) 0.29 (0.03-0.43) versus 0.52 (0.26-0.73), p = 0.0002). Among SLE patients, pleural fluid ANA titers ≥1:160 were more frequently found in patients with lupus pleuritis than in those with pleural effusion from causes other than lupus itself (85.7% versus 20.0%, p = 0.0152). Serum CRP levels were significantly increased in patients with lupus pleuritis compared with SLE patients with transudative pleural effusion (2.30 (0.30-5.66) versus 0.7 (0.12-1.47) mg/dl, p = 0.0062). In conclusion, pleural fluid ANA titer and serum CRP levels are significantly increased in lupus pleuritis. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Validation of an Argentine version of Lupus Quality of Life questionnaire.

PubMed

Machado Escobar, M A; Yacuzzi, M S; Martinez, R N; González Lucero, L; Bellomio, V I; Santana, M; Galindo, L; Mayer, M M; Barreira, J C; Sarano, J; Gomez, G; Collado, M V; Martinez, A; Orozco, M C; Betancur, G; Dal Pra, F; Sanchez, A; Juarez, V; Lucero, E V

2016-12-01

To determine reproducibility and validity of an Argentine version of the Lupus Quality of Life questionnaire (LupusQoL) and to determine cut-off values in the questionnaire. One hundred and forty-seven systemic lupus erythematosus patients (American College of Rheumatology 1982/1997) were assessed from April 2014 to July 2014. Demographic and socioeconomic variables were collected, as well as SELENA/SLEDAI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index Score, comorbidities and treatment data. Patients completed LupusQoL-Argentine version and European Quality of Life Questionnaire (EuroQoL-5D). Internal consistency and reliability were examined. Convergent validity with EuroQoL-5D was assessed through analysis of latent classes, which established homogeneous categories from the responses of each domain of LupusQoL and for the total. Out of 147 patients, 93.2% were female, mean age 36.4 ± 11.1 years, mean disease duration 2.7 ± 9 years, mean SELENA/SLEDAI 2.7 ± 3 points. The cut-off point that defined good or bad quality of life was 0.739 for EuroQoL 5D and 63 for LupusQoL. Cut-off values for each LupusQoL domain were also defined, creating two classes in each of them. There was moderate to high concordance to classify quality of life (Kappa = 0.74, 95% confidence interval = 0.54, 0.95). The Argentine version of LupusQoL is a valid, reliable and reproducible instrument to assess quality of life. In this study, cut-off points that allow the classification of patients regarding whether they have good or bad quality of life are established for the first time. © The Author(s) 2016.

Reducing FLI1 Levels in the MRL/lpr Lupus Mouse Model Impacts T Cell Function by Modulating Glycosphingolipid Metabolism

PubMed Central

Richard, Erin Morris; Thiyagarajan, Thirumagal; Bunni, Marlene A.; Basher, Fahmin; Roddy, Patrick O.; Siskind, Leah J.; Nietert, Paul J.; Nowling, Tamara K.

2013-01-01

Systemic Lupus erythematosus (SLE) is an autoimmune disease caused, in part, by abnormalities in cells of the immune system including B and T cells. Genetically reducing globally the expression of the ETS transcription factor FLI1 by 50% in two lupus mouse models significantly improves disease measures and survival through an unknown mechanism. In this study we analyze the effects of reducing FLI1 in the MRL/lpr lupus prone model on T cell function. We demonstrate that adoptive transfer of MRL/lpr Fli1 +/+ or Fli1 +/- T cells and B cells into Rag1-deficient mice results in significantly decreased serum immunoglobulin levels in animals receiving Fli1 +/- lupus T cells compared to animals receiving Fli1 +/+ lupus T cells regardless of the genotype of co-transferred lupus B cells. Ex vivo analyses of MRL/lpr T cells demonstrated that Fli1 +/- T cells produce significantly less IL-4 during early and late disease and exhibited significantly decreased TCR-specific activation during early disease compared to Fli1 +/+ T cells. Moreover, the Fli1 +/- T cells expressed significantly less neuraminidase 1 (Neu1) message and decreased NEU activity during early disease and significantly decreased levels of glycosphingolipids during late disease compared to Fli1 +/+ T cells. FLI1 dose-dependently activated the Neu1 promoter in mouse and human T cell lines. Together, our results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism. Reducing the expression of FLI1 or targeting the glycosphingolipid metabolic pathway in lupus may serve as a therapeutic approach to treating lupus. PMID:24040398

Reducing FLI1 levels in the MRL/lpr lupus mouse model impacts T cell function by modulating glycosphingolipid metabolism.

PubMed

Richard, Erin Morris; Thiyagarajan, Thirumagal; Bunni, Marlene A; Basher, Fahmin; Roddy, Patrick O; Siskind, Leah J; Nietert, Paul J; Nowling, Tamara K

2013-01-01

Systemic Lupus erythematosus (SLE) is an autoimmune disease caused, in part, by abnormalities in cells of the immune system including B and T cells. Genetically reducing globally the expression of the ETS transcription factor FLI1 by 50% in two lupus mouse models significantly improves disease measures and survival through an unknown mechanism. In this study we analyze the effects of reducing FLI1 in the MRL/lpr lupus prone model on T cell function. We demonstrate that adoptive transfer of MRL/lpr Fli1(+/+) or Fli1(+/-) T cells and B cells into Rag1-deficient mice results in significantly decreased serum immunoglobulin levels in animals receiving Fli1(+/-) lupus T cells compared to animals receiving Fli1(+/+) lupus T cells regardless of the genotype of co-transferred lupus B cells. Ex vivo analyses of MRL/lpr T cells demonstrated that Fli1(+/-) T cells produce significantly less IL-4 during early and late disease and exhibited significantly decreased TCR-specific activation during early disease compared to Fli1(+/+) T cells. Moreover, the Fli1(+/-) T cells expressed significantly less neuraminidase 1 (Neu1) message and decreased NEU activity during early disease and significantly decreased levels of glycosphingolipids during late disease compared to Fli1(+/+) T cells. FLI1 dose-dependently activated the Neu1 promoter in mouse and human T cell lines. Together, our results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism. Reducing the expression of FLI1 or targeting the glycosphingolipid metabolic pathway in lupus may serve as a therapeutic approach to treating lupus.

Lack of the Long Pentraxin PTX3 Promotes Autoimmune Lung Disease but not Glomerulonephritis in Murine Systemic Lupus Erythematosus

PubMed Central

Kulkarni, Onkar P.; Susanti, Heni Eka; Migliorini, Adriana; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans-Joachim

2011-01-01

The long pentraxin PTX3 has multiple roles in innate immunity. For example, PTX3 regulates C1q binding to pathogens and dead cells and regulates their uptake by phagocytes. It also inhibits P-selectin-mediated recruitment of leukocytes. Both of these mechanisms are known to be involved in autoimmunity and autoimmune tissue injury, e.g. in systemic lupus erythematosus, but a contribution of PTX3 is hypothetical. To evaluate a potential immunoregulatory role of PTX3 in autoimmunity we crossed Ptx3-deficient mice with Fas-deficient (lpr) C57BL/6 (B6) mice with mild lupus-like autoimmunity. PTX3 was found to be increasingly expressed in kidneys and lungs of B6lpr along disease progression. Lack of PTX3 impaired the phagocytic uptake of apoptotic T cells into peritoneal macrophages and selectively expanded CD4/CD8 double negative T cells while other immune cell subsets and lupus autoantibody production remained unaffected. Lack of PTX3 also aggravated autoimmune lung disease, i.e. peribronchial and perivascular CD3+ T cell and macrophage infiltrates of B6lpr mice. In contrast, histomorphological and functional parameters of lupus nephritis remained unaffected by the Ptx3 genotype. Together, PTX3 specifically suppresses autoimmune lung disease that is associated with systemic lupus erythematosus. Vice versa, loss-of-function mutations in the Ptx3 gene might represent a genetic risk factor for pulmonary (but not renal) manifestations of systemic lupus or other autoimmune diseases. PMID:21637713

Novel insights of microRNAs in the development of systemic lupus erythematosus.

PubMed

Le, Xiong; Yu, Xiang; Shen, Nan

2017-09-01

To provide a brief overview of recent progress in microRNA biogenesis and homeostasis, its function in immune system and systemic lupus erythematosus (SLE), as well as successful microRNA-based therapy in vivo. Stepwise microRNA biogenesis is elaborately regulated at multiple levels, ranging from transcription to ultimate function. Mature microRNAs have inhibitory effects on various biological molecules, which are crucial for stabilizing and normalizing differentiation and function of immune cells. Abnormality in microRNA expression contributes to dysfunction of lupus immune cells and resident cells in local tissues. Manipulation of dysregulated microRNAs in vivo through microRNA delivery or targeting microRNA might be promising for SLE treatment. Recent advances highlight that microRNAs are important in immunity, lupus autoimmunity and as potential therapy target for SLE.

Kikuchi–Fujimoto disease and systemic lupus erythematosus

PubMed Central

Baenas, Diego F; Diehl, Fernando A; Haye Salinas, María J; Riva, Verónica; Diller, Ana; Lemos, Pablo A

2016-01-01

Kikuchi–Fujimoto disease, or histiocytic necrotizing lymphadenitis, is an infrequent idiopathic disorder. It has been associated with autoimmune disorders, of which systemic lupus erythematosus is the most outstanding. The basis of its diagnosis relies on the histological examination of lymph nodes, which typically reveals necrosis surrounded by histiocytes with crescentic nucleus, immunoblasts and plasma cells, and absence of neutrophils. We report the case of a 27-year-old Argentinian female patient without any relevant past medical history to demonstrate the correlation between Kikuchi–Fujimoto disease and systemic lupus erythematosus. PMID:27418858

Systemic lupus erythematosus in a male patient

NASA Astrophysics Data System (ADS)

Sibarani, H.; Zubir, Z.

2018-03-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a broad spectrum of clinical presentations. Female to male ratio is approximately 9:1.A 20 years old male was admitted to HAM Hospital 3 months ago with chief complaint pain in both knees joint. After anamneses, physical examination and laboratory test the patient was diagnosed with systemic lupus erythematosus. The patient tested positive for ANA and anti-ds-DNA antibody test. The patient was with giving non-biologic DMARDS @myfortic 360mg, methylprednisolone, chloroquine and other symptomatic drugs.

Coincident systemic lupus erythematosus and psoriasis vulgaris: a case report.

PubMed

Wang, Y; Da, G; Yu, Y; Han, J; Li, H

2015-12-01

Psoriasis vulgaris is an autoimmune chronic inflammatory skin disease, but its association with other typical autoimmune disease such as systemic lupus erythematosus has only occasionally been reported. We presented a 25-year-old female who developed systemic lupus erythematosus associated with psoriasis vulgaris. Her conditions were in good control after she got administration of prednisolone (5 mg/day) and Tripterygium Wilfordii Hook (20 mg/day). It is necessary to integrate past history and physical examination to diagnose coincident SLE and psoriasis, and combined treatment with prednisolone and Tripterygium Wilfordii Hook proves effective.

Type I interferon signature in systemic lupus erythematosus.

PubMed

Bezalel, Shira; Guri, Keren Mahlab; Elbirt, Daniel; Asher, Ilan; Sthoeger, Zev Moshe

2014-04-01

Type I interferons (IFN) are primarily regarded as an inhibitor of viral replication. However, type I IFN, mainly IFNalpha, plays a major role in activation of both the innate and adaptive immune systems. Systemic lupus erythematosus (SLE) is a chronic, multi-systemic, inflammatory autoimmune disease with undefined etiology. SLE is characterized by dysregulation of both the innate and the adaptive immune systems. An increased expression of type I IFN-regulated genes, termed IFN signature, has been reported in patients with SLE. We review here the role of IFNalpha in the pathogenesis and course of SLE and the possible role of IFNalpha inhibition as a novel treatment for lupus patients.

Association between rs2431697 T allele on 5q33.3 and systemic lupus erythematosus: case-control study and meta-analysis.

PubMed

Tang, Zhao-Ming; Wang, Ping; Chang, Pan-Pan; Hasahya, Tony; Xing, Hui; Wang, Jin-Ping; Hu, Li-Hua

2015-11-01

rs2431697 is located on 5q33.3, between pituitary tumor-transforming gene 1 and miR-146a. Several studies have estimated the association between rs2431697 and systemic lupus erythematosus risk. However, the results were inconsistent. A case-control study was carried out to explore the association between rs2431697 and systemic lupus erythematosus risk in a central Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. Our case-control study included 322 cases and 353 controls. rs2431697 T allele was associated with increased risk of systemic lupus erythematosus (odds ratios (ORs) = 1.461, 95% confidence intervals (CI) 1.091-1.957, P = 0.011). The association was stronger between T allele and the risk of anti-double-stranded DNA (dsDNA)-positive systemic lupus erythematosus (OR = 2.510, 95% CI 1.545-4.077, P < 0.001). The meta-analyses included 8648 systemic lupus erythematosus patients and 10947 controls. rs2431697 T allele had an overall OR of 1.262 (95% CI 1.205-1.323, P < 0.001) under fixed-effects model. After stratified by ethnicity, I (2) reduced from 24.3 to 0 %. T allele had an OR of 1.213 (95% CI 1.145-1.284, P < 0.001) in European descendant and 1.365 (95% CI 1.259-1.480, P < 0.001) in Asian under fixed-effects model. Data on women were also extracted, and T allele had an OR of 1.337 (95% CI 1.162-1.539, P < 0.001) under random-effects model. The pooled ORs were not influenced by each study in sensitivity analyses. There were no publication biases observed in these analyses. The results from our case-control study and the meta-analyses indicate that rs2431697 T allele significantly associates with the increased risk of systemic lupus erythematosus.

Type I Interferon in the Pathogenesis of Lupus

PubMed Central

Crow, Mary K.

2014-01-01

Investigations of patients with systemic lupus erythematosus (SLE) have applied insights from studies of the innate immune response to define type I interferon (IFN-I), with IFN-α the dominant mediator, as central to the pathogenesis of this prototype systemic autoimmune disease. Genetic association data identify regulators of nucleic acid degradation and components of TLR-independent, endosomal TLR-dependent, and IFN-I signaling pathways as contributors to lupus disease susceptibility. Together with a gene expression signature characterized by IFNI-induced gene transcripts in lupus blood and tissue, those data support the conclusion that many of the immunologic and pathologic features of this disease are a consequence of a persistent self-directed immune reaction driven by IFN-I and mimicking a sustained anti-virus response. This expanding knowledge of the role of IFN-I and the innate immune response suggests candidate therapeutic targets that are being tested in lupus patients. PMID:24907379

Using the American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria to determine the diagnosis of systemic lupus erythematosus (SLE) in patients with subacute cutaneous lupus erythematosus (SCLE).

PubMed

Tiao, Janice; Feng, Rui; Carr, Kasey; Okawa, Joyce; Werth, Victoria P

2016-05-01

Approximately 50% of patients with subacute cutaneous lupus erythematosus (SCLE) meet criteria for systemic lupus erythematosus (SLE). The Systemic Lupus International Collaborating Clinics (SLICC) developed new SLE criteria to improve the American College of Rheumatology (ACR) criteria but the SLICC criteria have not been evaluated in patients with SCLE. We sought to determine how patients with SCLE/SLE meet the ACR and SLICC criteria to compare the 2 sets of criteria. This was a retrospective analysis of 107 patients with SCLE enrolled in a database at the University of Pennsylvania. Patients with SCLE/SLE were more likely than those with only SCLE to have oral ulcers, positive anti-double-stranded DNA antibodies, and positive antinuclear antibody test findings using both sets of criteria. Patients with SCLE/SLE were also more likely to have low complement using the SLICC criteria. There was a statistically insignificant increase in individuals meeting the SLICC criteria. Not all patients received comprehensive laboratory testing. Most patients with SCLE who formally meet criteria for SLE do so based on the laboratory and mucocutaneous criteria. Neither the ACR nor SLICC criteria distinguish patients with SCLE and major internal disease from patients with SCLE without major internal disease. Published by Elsevier Inc.

Autoantibodies against complement components in systemic lupus erythematosus - role in the pathogenesis and clinical manifestations.

PubMed

Hristova, M H; Stoyanova, V S

2017-12-01

Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus. Genetic defects in the complement as well as functional deficiency due to antibodies against its components lead to different pathological conditions, usually clinically presented. Among them hypocomplementemic urticarial vasculitis, different types of glomerulonephritis as dense deposit disease, IgA nephropathy, atypical haemolytic uremic syndrome and lupus nephritis are very common. These antibodies cause conformational changes leading to pathological activation or inhibition of complement with organ damage and/or limited capacity of the immune system to clear immune complexes and apoptotic debris. Finally, we summarize the role of complement antibodies in the pathogenesis of systemic lupus erythematosus and discuss the mechanism of some related clinical conditions such as infections, thyroiditis, thrombosis, acquired von Willebrand disease, etc.

Ethnicity and mortality from systemic lupus erythematosus in the US.

PubMed

Krishnan, E; Hubert, H B

2006-11-01

To study ethnic differences in mortality from systemic lupus erythematosus (lupus) in two large, population-based datasets. We analysed the national death data (1979-98) from the National Center for Health Statistics (Hyattsville, Maryland, USA) and hospitalisation data (1993-2002) from the Nationwide Inpatient Sample (NIS), the largest hospitalisation database in the US. The overall, unadjusted, lupus mortality in the National Center for Health Statistics data was 4.6 per million, whereas the proportion of in-hospital mortality from the NIS was 2.9%. African-Americans had disproportionately higher mortality risk than Caucasians (all-cause mortality relative risk adjusted for age = 1.24 (women), 1.36 (men); lupus mortality relative risk = 3.91 (women), 2.40 (men)). Excess risk was found among in-hospital deaths (odds ratio adjusted for age = 1.4 (women), 1.3 (men)). Lupus death rates increased overall from 1979 to 98 (p<0.001). The proportional increase was greatest among African-Americans. Among Caucasian men, death rates declined significantly (p<0.001), but rates did not change substantially for African-American men. The African-American:Caucasian mortality ratio rose with time among men, but there was little change among women. In analyses of the NIS data adjusted for age, the in-hospital mortality risk decreased with time among Caucasian women (p<0.001). African-Americans with lupus have 2-3-fold higher lupus mortality risk than Caucasians. The magnitude of the risk disparity is disproportionately higher than the disparity in all-cause mortality. A lupus-specific biological factor, as opposed to socioeconomic and access-to-care factors, may be responsible for this phenomenon.

A rare case of unilateral discoid lupus erythematosus mimicking lupus vulgaris.

PubMed

Verma, Parul; Pathania, Sucheta; Kubba, Asha

2017-11-08

Discoidlupus erythematosus (DLE) is a chronic type of cutaneous lupus erythematosus which can present in various morphologies, and the diagnosis can be rather confounding. Prompt evaluation and treatment is necessary to prevent disfigurement and systemic involvement associated with DLE. The following case presented a diagnostic dilemma as the lesion mimicked lupus vulgaris. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus

PubMed Central

Wang, Jianxun; Zeng, Li-Fan; Bronson, Roderick; Finnell, Michele; Terhorst, Cox; Kyttaris, Vasileios C.; Zhang, Zhong-Yin; Kontaridis, Maria I.

2016-01-01

Systemic lupus erythematosus (SLE) is a devastating multisystemic autoimmune disorder. However, the molecular mechanisms underlying its pathogenesis remain elusive. Some patients with Noonan syndrome, a congenital disorder predominantly caused by gain-of-function mutations in the protein tyrosine phosphatase SH2 domain–containing PTP (SHP2), have been shown to develop SLE, suggesting a functional correlation between phosphatase activity and systemic autoimmunity. To test this directly, we measured SHP2 activity in spleen lysates isolated from lupus-prone MRL/lpr mice and found it was markedly increased compared with that in control mice. Similar increases in SHP2 activity were seen in peripheral blood mononuclear cells isolated from lupus patients relative to healthy patients. To determine whether SHP2 alters autoimmunity and related immunopathology, we treated MRL/lpr mice with an SHP2 inhibitor and found increased life span, suppressed crescentic glomerulonephritis, reduced spleen size, and diminished skin lesions. SHP2 inhibition also reduced numbers of double-negative T cells, normalized ERK/MAPK signaling, and decreased production of IFN-γ and IL-17A/F, 2 cytokines involved in SLE-associated organ damage. Moreover, in cultured human lupus T cells, SHP2 inhibition reduced proliferation and decreased production of IFN-γ and IL-17A/F, further implicating SHP2 in lupus-associated immunopathology. Taken together, these data identify SHP2 as a critical regulator of SLE pathogenesis and suggest targeting of its activity as a potent treatment for lupus patients. PMID:27183387

Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus.

PubMed

Wang, Jianxun; Mizui, Masayuki; Zeng, Li-Fan; Bronson, Roderick; Finnell, Michele; Terhorst, Cox; Kyttaris, Vasileios C; Tsokos, George C; Zhang, Zhong-Yin; Kontaridis, Maria I

2016-06-01

Systemic lupus erythematosus (SLE) is a devastating multisystemic autoimmune disorder. However, the molecular mechanisms underlying its pathogenesis remain elusive. Some patients with Noonan syndrome, a congenital disorder predominantly caused by gain-of-function mutations in the protein tyrosine phosphatase SH2 domain-containing PTP (SHP2), have been shown to develop SLE, suggesting a functional correlation between phosphatase activity and systemic autoimmunity. To test this directly, we measured SHP2 activity in spleen lysates isolated from lupus-prone MRL/lpr mice and found it was markedly increased compared with that in control mice. Similar increases in SHP2 activity were seen in peripheral blood mononuclear cells isolated from lupus patients relative to healthy patients. To determine whether SHP2 alters autoimmunity and related immunopathology, we treated MRL/lpr mice with an SHP2 inhibitor and found increased life span, suppressed crescentic glomerulonephritis, reduced spleen size, and diminished skin lesions. SHP2 inhibition also reduced numbers of double-negative T cells, normalized ERK/MAPK signaling, and decreased production of IFN-γ and IL-17A/F, 2 cytokines involved in SLE-associated organ damage. Moreover, in cultured human lupus T cells, SHP2 inhibition reduced proliferation and decreased production of IFN-γ and IL-17A/F, further implicating SHP2 in lupus-associated immunopathology. Taken together, these data identify SHP2 as a critical regulator of SLE pathogenesis and suggest targeting of its activity as a potent treatment for lupus patients.

Longitudinal analysis of varicella-zoster virus-specific antibodies in systemic lupus erythematosus: No association with subclinical viral reactivations or lupus disease activity.

PubMed

Rondaan, C; van Leer, C C; van Assen, S; Bootsma, H; de Leeuw, K; Arends, S; Bos, N A; Westra, J

2018-07-01

Systemic lupus erythematosus (SLE) patients are at high risk of herpes zoster. Previously, we found increased immunoglobulin (Ig)G levels against varicella-zoster virus (VZV) in SLE patients compared to controls, while antibody levels against diphtheria and cellular immunity to VZV were decreased. We aimed to test our hypothesis that increased VZV-IgG levels in SLE result from subclinical VZV reactivations, caused by stress because of lupus disease activity or immunosuppressive drug use. Methods Antibody levels to VZV (IgG, IgA, IgM), total IgG and VZV-DNA were longitudinally determined in the serum of 34 SLE patients, using enzyme-linked immunosorbent assay and polymerase chain reaction. Clinical data were retrieved from medical records. Reactivation of VZV was defined as an at least fivefold rise in VZV-IgG or presence of VZV-IgM or VZV-DNA. Generalized estimating equations (GEE) were used to longitudinally analyse associations between antibody levels, lupus disease activity and medication use. Systemic Lupus Erythematosus Disease Activity Index, anti-double-stranded DNA and complement levels were used as indicators of lupus disease activity. Results A VZV reactivation was determined in 11 patients (33%). In at least five of them, herpes zoster was clinically overt. No association between SLE disease activity or medication use and VZV-specific antibody levels was found. There was a weak association between total IgG and VZV-IgG. Conclusions Our results indicate that increased VZV-IgG levels in SLE do not result from frequent subclinical VZV reactivations, and are not associated with lupus disease activity. Increased VZV-IgG can only partially be explained by hypergammaglobulinaemia.

Metabolic syndrome in Iranian patients with systemic lupus erythematosus and its determinants.

PubMed

Fatemi, Alimohammad; Ghanbarian, Azadeh; Sayedbonakdar, Zahra; Kazemi, Mehdi; Smiley, Abbas

2018-06-01

The aim of this study was to determine the prevalence of metabolic syndrome (MetS) in Iranian patients with systemic lupus erythematosus (SLE) and its determinants. In a cross-sectional study, 98 patients with SLE and 95 controls were enrolled. Prevalence of MetS was determined based on American Heart Association and National Heart, Lung, and Blood Institute (AHA/NHLBI) and 2009 harmonizing criteria. In addition, demographic features and lupus characteristics such as disease duration, pharmacological treatment, laboratory data, SLE disease activity index (SLEDAI), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage index (SDI) were recorded. The predictors of MetS were obtained by backward stepwise regression analysis. Using AHA/NHLBI, MetS was observed in 35 (35.7%) patients and 28 (29.8%) controls (P = 0.4). Using harmonizing criteria, MetS was observed in 37 (37.7%) patients and 33 (35.1%) controls (P = 0.7). There was no difference in frequency distribution of MetS components between the patients and the controls. In multivariate regression analysis, low C3, blood urea nitrogen (BUN), and body mass index were independent determinants of MetS in lupus patients. BUN, low C3, and body mass index were the major determinants of MetS in lupus patients.

Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

PubMed

Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

2016-12-01

We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.

Lupus nephritis susceptibility loci in women with systemic lupus erythematosus.

PubMed

Chung, Sharon A; Brown, Elizabeth E; Williams, Adrienne H; Ramos, Paula S; Berthier, Celine C; Bhangale, Tushar; Alarcon-Riquelme, Marta E; Behrens, Timothy W; Criswell, Lindsey A; Graham, Deborah Cunninghame; Demirci, F Yesim; Edberg, Jeffrey C; Gaffney, Patrick M; Harley, John B; Jacob, Chaim O; Kamboh, M Ilyas; Kelly, Jennifer A; Manzi, Susan; Moser-Sivils, Kathy L; Russell, Laurie P; Petri, Michelle; Tsao, Betty P; Vyse, Tim J; Zidovetzki, Raphael; Kretzler, Matthias; Kimberly, Robert P; Freedman, Barry I; Graham, Robert R; Langefeld, Carl D

2014-12-01

Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5×10(-7)), 16p12 (SLC5A11; P=5.1×10(-7)), 6p22 (ID4; P=7.4×10(-7)), and 8q24.12 (HAS2, SNTB1; P=1.1×10(-6)). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7×10(-5), respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5×10(-6)). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci. Copyright © 2014 by the American Society of Nephrology.

Pure cutaneous lupus erythematosus in a population of African descent in French Guiana: a retrospective population-based description.

PubMed

Deligny, C; Marie, D Sainte; Clyti, E; Arfi, S; Couppié, P

2012-11-01

The objective of this study was to examine the characteristics of cutaneous lupus erythematosus, excluding systemic lupus erythematosus (SLE), in patients of African descent. Indeed, since the description of subacute cutaneous lupus erythematosus (SCLE), which had been included in chronic cutaneous lupus erythematosus (CCLE), there has been no description of the disease in black patients. In 2000, we performed a retrospective epidemiological study by querying multiple sources to identify all patients with lupus in French Guiana--a part of France in South America having western living conditions, free healthcare and 157,000 inhabitants, most of whom are of African origin. We found 45 patients with pure cutaneous lupus, which included CCLE (mostly discoid), SCLE and bullous lupus. The disease characteristics of these patients exhibited few differences compared with those of the Caucasian patients cited in the literature. However, the age of onset for our patients of African descent was younger than that of Caucasian patients. In contrast to the race-related differences reported for SLE, we found no major differences in terms of demographic, clinical and biological presentation between this cohort of pure cutaneous lupus erythematosus patients of African origin and Caucasian patients with similar forms of lupus.

Environmental Exposures, Epigenetic Changes and the Risk of Lupus

PubMed Central

Somers, Emily C; Richardson, Bruce C

2013-01-01

A dose-dependent combination of environmental exposures, estrogenic hormones and genetic predisposition is thought to be required for lupus to develop and flare, but how the environment modifies the immune system in genetically predisposed people is unclear. Current evidence indicates that environmental agents that inhibit DNA methylation can convert normal antigen-specific CD4+ T lymphocytes into autoreactive, cytotoxic, pro-inflammatory cells that are sufficient to cause lupus-like autoimmunity in animal models, and that the same changes in DNA methylation characterize CD4+ T cells from patients with active lupus. Environmental agents implicated in inhibiting T cell DNA methylation include the lupus-inducing drugs procainamide and hydralazine, as well as diet, and agents causing oxidative stress, such as smoking, UV light exposure, and infections, which have been associated with lupus onset or disease activity. Other studies demonstrate that demethylated T cells cause only anti-DNA antibodies in mice lacking a genetic predisposition to lupus, but are sufficient to cause lupus-like autoimmunity in genetically predisposed mice and likely people, and that estrogens augment the disease. Collectively, these studies suggest that environmental agents that inhibit DNA methylation, together with lupus genes and estrogens or endocrine disruptors, combine in a dose-dependent fashion to cause lupus flares. PMID:24763540

Intravenous cyclophosphamide pulse therapy in Japanese children with systemic lupus erythematosus.

PubMed

Igarashi, Toru; Igarashi, Tsutomu; Shimizu, Akira; Itoh, Yasuhiko

2013-01-01

Intravenous cyclophosphamide (IVCY) pulse therapy has been used for lupus nephritis since the latter half of the 1980s; it has been shown to be effective for lupus nephritis and vasculitis and has become a standard therapy for the diffuse proliferative type of lupus nephritis in adults. IVCY therapy has also come to be used in children. This paper reports the long-term outcomes of IVCY therapy in children. Six female patients (age range, 13 to 18 years) with systemic lupus erythematosus (SLE) were enrolled in this retrospective study. Three patients had lupus nephritis (World Health Organization class IIb, IVa, IVc), 2 had central nervous system (CNS) lupus, and 1 had neither lupus nephritis nor CNS lupus. The mean pretreatment SLE disease activity index (SLEDAI) score was 18.8 ± 4.6. Cyclophosphamide (initial dose, 500 mg/m(2)) was administered intravenously each month for 6 months and then given every 3 months for maintenance. Prednisolone was given in dosages ranging from 5 to 60 mg/day, adjusted according to laboratory data and clinical symptoms. Levels of C3, C4, CH50, and creatinine; the SLEDAI score; and the SLE responder index were monitored and evaluated. The SLE responder index was considered to have improved if the SLEDAI score had decreased by 4 points or more after 52 weeks. Prednisolone doses were reduced in all patients. Because methylprednisolone pulse therapy was administered before IVCY therapy, some patients had low titers of immunoglobin G antibodies against double-stranded DNA at the start of IVCY therapy. All patients had low serum creatinine levels. Proteinuria resolved in 1 of the 3 patients with lupus nephritis. The SLEDAI scores improved after 52 weeks in 5 of 6 patients (mean, 5.2 ± 2.6). No patients had severe bone marrow suppression or hemorrhagic cystitis during IVCY pulse therapy. IVCY pulse therapy for SLE in children achieved good long-term outcomes with no serious adverse effects, such as digestive symptoms, bone marrow suppression, infection, and hemorrhagic cystitis. IVCY pulse therapy for children with SLE has recently been approved by the Ministry of Health, Labour and Welfare. Accordingly, this paper might become a guideline for this treatment.

C5a induces caspase-dependent apoptosis in brain vascular endothelial cells in experimental lupus.

PubMed

Mahajan, Supriya D; Tutino, Vincent M; Redae, Yonas; Meng, Hui; Siddiqui, Adnan; Woodruff, Trent M; Jarvis, James N; Hennon, Teresa; Schwartz, Stanley; Quigg, Richard J; Alexander, Jessy J

2016-08-01

Blood-brain barrier (BBB) dysfunction complicates central nervous system lupus, an important aspect of systemic lupus erythematosus. To gain insight into the underlying mechanism, vascular corrosion casts of brain were generated from the lupus mouse model, MRL/lpr mice and the MRL/MpJ congenic controls. Scanning electron microscopy of the casts showed loss of vascular endothelial cells in lupus mice compared with controls. Immunostaining revealed a significant increase in caspase 3 expression in the brain vascular endothelial cells, which suggests that apoptosis could be an important mechanism causing cell loss, and thereby loss of BBB integrity. Complement activation occurs in lupus resulting in increased generation of circulating C5a, which caused the endothelial layer to become 'leaky'. In this study, we show that C5a and lupus serum induced apoptosis in cultured human brain microvascular endothelial cells (HBMVECs), whereas selective C5a receptor 1 (C5aR1) antagonist reduced apoptosis in these cells, demonstrating C5a/C5aR1-dependence. Gene expression of initiator caspases, caspase 1 and caspase 8, and pro-apoptotic proteins death-associated protein kinase 1, Fas-associated protein (FADD), cell death-inducing DNA fragmentation factor 45 000 MW subunit A-like effector B (CIDEB) and BCL2-associated X protein were increased in HBMVECs treated with lupus serum or C5a, indicating that both the intrinsic and extrinsic apoptotic pathways could be critical mediators of brain endothelial cell apoptosis in this setting. Overall, our findings suggest that C5a/C5aR1 signalling induces apoptosis through activation of FADD, caspase 8/3 and CIDEB in brain endothelial cells in lupus. Further elucidation of the underlying apoptotic mechanisms mediating the reduced endothelial cell number is important in establishing the potential therapeutic effectiveness of C5aR1 inhibition that could prevent and/or reduce BBB alterations and preserve the physiological function of BBB in central nervous system lupus. © 2016 John Wiley & Sons Ltd.

Neuropsychiatric Systemic Lupus Erythematosus

PubMed Central

Popescu, Alexandra; Kao, Amy H

2011-01-01

Neuropsychiatric systemic lupus erythematosus (NPSLE) is the least understood, yet perhaps the most prevalent manifestation of lupus. The pathogenesis of NPSLE is multifactorial and involves various inflammatory cytokines, autoantibodies, and immune complexes resulting in vasculopathic, cytotoxic and autoantibody-mediated neuronal injury. The management of NPSLE is multimodal and has not been subjected to rigorous study. Different treatment regimens include nonsteroidal anti-inflammatory drugs, anticoagulation, and immunosuppressives such as cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate. For refractory NPSLE, intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab have been used. Adjunctive symptomatic treatment complements these therapies by targeting mood disorders, psychosis, cognitive impairment, seizures or headaches. Several new biological agents are being tested including Belimumab, a human monoclonal antibody that targets B lymphocyte stimulator. This review focuses on the pathophysiology, treatment, and new potential therapies for neuropsychiatric manifestations of systemic lupus erythematosus. PMID:22379459

[Lupus enteritis as initial manifestation of systemic lupus erythematosus. Report of one case].

PubMed

Barrera O, Manuel; Barrera M, Rodrigo; de la Rivera V, Matías; Vela U, Javier; Mönckeberg F, Gustavo

2017-10-01

Although gastrointestinal symptoms are not rare in Systemic lupus erythematosus, enteritis is an atypical manifestation of the disease. We report a 54 year-old woman who presented acute symptoms of diarrhea, fever and abdominal pain, receiving empiric antibiotic therapy for bacterial enteritis with no response. Computed tomography showed diffuse small intestine inflammation and serositis. Antinuclear antibodies, anti-Ro and anti-La were positive on blood tests. A lupic enteropathy was diagnosed and steroid treatment was initiated, with subsequent clinical improvement.

Integrative medicine for managing the symptoms of lupus nephritis: A protocol for systematic review and meta-analysis.

PubMed

Choi, Tae-Young; Jun, Ji Hee; Lee, Myeong Soo

2018-03-01

Integrative medicine is claimed to improve symptoms of lupus nephritis. No systematic reviews have been performed for the application of integrative medicine for lupus nephritis on patients with systemic lupus erythematosus (SLE). Thus, this review will aim to evaluate the current evidence on the efficacy of integrative medicine for the management of lupus nephritis in patients with SLE. The following electronic databases will be searched for studies published from their dates of inception February 2018: Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as 6 Korean medical databases (Korea Med, the Oriental Medicine Advanced Search Integrated System [OASIS], DBpia, the Korean Medical Database [KM base], the Research Information Service System [RISS], and the Korean Studies Information Services System [KISS]), and 1 Chinese medical database (the China National Knowledge Infrastructure [CNKI]). Study selection, data extraction, and assessment will be performed independently by 2 researchers. The risk of bias (ROB) will be assessed using the Cochrane ROB tool. This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide healthcare practice and policy. PROSPERO 2018 CRD42018085205.

[A case of systemic lupus erythematosus complicated with psoriasis vulgaris].

PubMed

Shidara, Kumi; Soejima, Makoto; Shiseki, Mariko; Ohta, Syuji; Nishinarita, Makoto

2003-12-01

A 49-years-old female admitted to our hospital because of skin eruptions on the extremities in 1985. She had suffered from polyarthralgia, skin eruptions since 1983. Physical examinations revealed discoid lesion, central nervous system involvement, and polyarthritis. Laboratory tests revealed leukopenia, thrombocytopenia, and hypocomplementemia. Antinuclear antibody, ant-DNA antibody, LE test were positive. From these findings, she was diagnosed as systemic lupus erythematosus (SLE). She developed lupus peritonitis in 1990 and 1994, which was successfully treated by steroid pulse therapy. Since then, the activity of SLE was in good control under administration of prednisolone 10 mg/day. Chilblain lupus was seen from 1993, Raynaud's phenomenon from 1996, and she further developed subcutaneous induration on her chest, back and upper extremities in 1999. Skin biopsy findings were compatible with lupus panniculitis. In 2002, erythematous patches with scales were observed on her right hand and left knee, and these skin lesions were histologically diagnosed as psoriasis vulgaris. An autoimmune response similar to SLE is speculated in psoriasis. We describe a rare case of SLE with various skin lesions including psoriasis vulgaris.

Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosenpud, J.D.; Montanaro, A.; Hart, M.V.

1984-08-01

Accelerated coronary artery disease and myocardial infarction in young patients with systemic lupus erythematosus is well documented; however, the prevalence of coronary involvement is unknown. Accordingly, 26 patients with systemic lupus were selected irrespective of previous cardiac history to undergo exercise thallium-201 cardiac scintigraphy. Segmental perfusion abnormalities were present in 10 of the 26 studies (38.5 percent). Five patients had reversible defects suggesting ischemia, four patients had persistent defects consistent with scar, and one patient had both reversible and persistent defects in two areas. There was no correlation between positive thallium results and duration of disease, amount of corticosteroid treatment,more » major organ system involvement or age. Only a history of pericarditis appeared to be associated with positive thallium-201 results (p less than 0.05). It is concluded that segmental myocardial perfusion abnormalities are common in patients with systemic lupus erythematosus. Whether this reflects large-vessel coronary disease or small-vessel abnormalities remains to be determined.« less

Is there an association between systemic lupus erythematosus and periodontal disease?

PubMed

Calderaro, Débora Cerqueira; Ferreira, Gilda Aparecida; de Mendonça, Santuza Maria Souza; Corrêa, Jôice Dias; Santos, Fabrícia Xavier; Sanção, João Guilherme Capinam; da Silva, Tarcília Aparecida; Teixeira, Antônio Lúcio

2016-01-01

Periodontal disease results from the interaction between pathogenic bacteria that colonize supragingival and subgingival biofilms and the host, triggering an inflammatory response, with systemic effects leading to immune-mediated destruction of the attachment apparatus and loss of supporting alveolar bone. Immunological pathways and predisposing genetic factors common to periodontal disease and rheumatic diseases, including systemic lupus erythematosus, have been described. Case reports have suggested greater severity of periodontal disease in patients with systemic lupus erythematosus. However, studies evaluating the influence of the treatment of one disease on the clinical and laboratory manifestations of the other have yielded conflicting results. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Purified umbilical cord derived mesenchymal stem cell treatment in a case of systemic lupus erythematosus.

PubMed

Phillips, Christopher D; Wongsaisri, Pornpatcharin; Htut, Thein; Grossman, Terry

2017-12-01

Systemic lupus erythematosus (SLE) is a multiple organ system autoimmune disorder for which there is no known cure. We report a case of a young adult lady with SLE and Sjogren's with diagnostic and clinical resolution following purified umbilical cord derived mesenchymal stem cell (MSC) and globulin component protein macrophage activating factor (GcMAF) therapy in a combined multidisciplinary integrative medicine protocol. Our patient had complete reversal of all clinical and laboratory markers. We recommend a prospective randomized double blind study to assess the sustained efficacy of MSC and GcMAF in the treatment of autoimmune connective tissue diseases such as systemic lupus erythematosus.

Systemic lupus erythematosus due to Epstein-Barr virus or Epstein-Barr virus infection provocating acute exacerbation of systemic lupus erythematosus?

PubMed

Kasapcopur, Ozgur; Ergul, Yakup; Kutlug, Seyhan; Candan, Cengiz; Camcioglu, Yildiz; Arisoy, Nil

2006-06-01

Systemic lupus erythematosus (SLE) is a rheumatologic disease characterized by an inflammatory destruction of the target organ systems of the body in an unknown way by autoantibodies formed against self-antigens. Infectious agents like Epstein-Barr virus (EBV), cytomegalovirus and parvovirus B19 may have a role in the occurrence or the exacerbation of the SLE. In this report, the clinical follow-up of a 14-year-old girl diagnosed with SLE following an EBV infection with bicytopenia, lymphadenomegaly and hepatomegaly is discussed. This case could support the role of viral infections in the etiology of SLE.

Activated protein C attenuates systemic lupus erythematosus and lupus nephritis in MRL-Fas(lpr) mice.

PubMed

Lichtnekert, Julia; Rupanagudi, Khader Valli; Kulkarni, Onkar P; Darisipudi, Murthy Narayana; Allam, Ramanjaneyulu; Anders, Hans-Joachim

2011-09-15

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease leading to inflammatory tissue damage in multiple organs (e.g., lupus nephritis). Current treatments including steroids, antimalarials, and immunosuppressive drugs have significant side effects. Activated protein C is a natural protein with anticoagulant and immunomodulatory effects, and its recombinant version has been approved by the U.S. Food and Drug Administration to treat severe sepsis. Given the similarities between overshooting immune activation in sepsis and autoimmunity, we hypothesized that recombinant activated protein C would also suppress SLE and lupus nephritis. To test this concept, autoimmune female MRL-Fas(lpr) mice were injected with either vehicle or recombinant human activated protein C from week 14-18 of age. Activated protein C treatment significantly suppressed lupus nephritis as evidenced by decrease in activity index, glomerular IgG and complement C3 deposits, macrophage counts, as well as intrarenal IL-12 expression. Further, activated protein C attenuated cutaneous lupus and lung disease as compared with vehicle-treated MRL-Fas(lpr) mice. In addition, parameters of systemic autoimmunity, such as plasma cytokine levels of IL-12p40, IL-6, and CCL2/MCP-1, and numbers of B cells and plasma cells in spleen were suppressed by activated protein C. The latter was associated with lower total plasma IgM and IgG levels as well as lower titers of anti-dsDNA IgG and rheumatoid factor. Together, recombinant activated protein C suppresses the abnormal systemic immune activation in SLE of MRL-Fas(lpr) mice, which prevents subsequent kidney, lung, and skin disease. These results implicate that recombinant activated protein C might be useful for the treatment of human SLE.

Atorvastatin therapy reduces interferon-regulated chemokine CXCL9 plasma levels in patients with systemic lupus erythematosus.

PubMed

Ferreira, G A; Teixeira, A L; Sato, E I

2010-07-01

A recent study showed transcriptional levels of interferon-inducible chemokines in peripheral blood cells were associated with disease activity and organ damage in systemic lupus erythematosus, and may be useful in monitoring disease activity and prognosis. Our objective was to evaluate the capacity of atorvastatin to reduce plasma levels of interferon-regulated chemokines (CCL2, CCL3 and CXCL9) and to study the correlation between these chemokines and disease activity in patients with systemic lupus erythematosus. Eighty-eight female patients with systemic lupus erythematosus were divided into two groups: 64 receiving 20 mg/day of atorvastatin (intervention group) and 24 without atorvastatin (control group). All patients were followed for 8 weeks. At baseline and after 8 weeks laboratory tests were performed for all patients. Plasma levels of chemokines were measured by ELISA using commercial kits (DuoSet, R&D Systems, Minneapolis, USA). In a univariate analysis we found correlation between CCL2, CCL3 and CXCL9 plasma levels and SLEDAI score. In the intervention group we observed a significant decrease in CXCL9 plasma levels comparing baseline and levels at the end of the study (p = 0.04); however, no differences were observed regarding CCL2 or CCL3 plasma levels in this study. No significant difference was observed in the plasma levels of these chemokines in the control group. We conclude that treatment with atorvastatin was associated with a significant decrease in the plasma levels of CXCL9 in patients with systemic lupus erythematosus. As the plasma levels of CXCL9 correlated with the SLEDAI score, we ask whether reducing levels of this chemokine could help to control systemic lupus erythematosus activity.

Cytokines in relation to autoantibodies before onset of symptoms for systemic lupus erythematosus.

PubMed

Eriksson, C; Rantapää-Dahlqvist, S

2014-06-01

A number of cytokines and chemokines were analysed and related to autoantibodies in blood samples pre-dating the onset of symptoms of systemic lupus erythematosus. Thirty-five patients with systemic lupus erythematosus (American College of Rheumatology criteria) were identified as having donated blood samples, prior to symptom onset, to the Biobank of northern Sweden. Altogether, 140 age- and sex-matched controls were also identified. The concentrations of interferon-α, interleukin-4, interleukin-9, interleukin-10, interferon inducible protein-10 and monocyte chemotactic protein-1 were analysed using multiplex technology and related to autoantibodies (ANA, ENA, anti-dsDNA and anti-histone antibodies) analysed from the same blood sample. The interferon-γ inducible protein-10 levels were higher in the pre-symptomatic individuals than in controls (p < 0.05) and correlated with interferon-α (p < 0.01). The interferon-γ inducible protein-10 and interferon-α concentrations were significantly increased in individuals positive for autoantibodies: interferon-γ inducible protein-10 for ANA; anti-SSA/Ro and anti-Jo-1 antibodies; interferon-α with anti-SSB/La antibodies. The levels of interleukin-10, interferon-γ inducible protein-10 and monocyte chemotactic protein-1 increased significantly from the pre-symptomatic individuals to after onset of systemic lupus erythematosus. An increased concentration of interferon-γ inducible protein-10 pre-dated the onset of systemic lupus erythematosus and was related to autoantibodies before the onset of disease. The levels of interferon-γ inducible protein-10 and interferon-α were correlated. These findings support the proposal that the interferon system is important early in the pathogenesis of systemic lupus erythematosus and autoantibody formation. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

An invisible student population: Accommodating and serving college students with lupus.

PubMed

Agarwal, Neelam; Kumar, Vinod

2017-01-01

Systemic Lupus Erythematosus (SLE), or lupus, is a chronic autoimmune disorder. Individuals with lupus face unique psychosocial and emotional challenges such as living with the unpredictability of the disease, symptoms such as fatigue, pain and depression, anxiety, cognitive problems, and coping with stress. This article attempts to shed light on the role that lupus plays in the lives of college students in their academics and other unique psychosocial needs. The author uses a single case study method based on the lived experience of a student with lupus. The method adopted is used as a means to provide anecdotal information about specific areas to consider when providing services to students living with this condition. Findings from this one case study identified some of the accommodations available to help students in higher education that may even vary for two students with same diagnosis of lupus. The paper presents some of the innovative strategies that can be used by practitioners while working with these students in higher education. These strategies can provide helpful support for students with lupus with the recommended academic accommodations.

[Current aspects of systemic lupus erythematosus in Dakar. About 74 cases].

PubMed

Fall, S; Dia, D; Ka, E F; Diallo, S; Pouye, A; Kane, A; Niang, A; Dieng, M T; Ka, M M; Diouf, B; Ndiaye, B; Moreira, Diop T

2007-01-01

previously reported studies on systemic lupus erythematosus in Senegal were more then ten years old and reported few cases of patients. Our objectives were to update epidemiological, clinical, laboratory and evolutive aspects of systemic lupus erythematosus throughout a study of 74 patients. we conducted a retrospective study in the internal medicine and the dermatology units of the university teaching hospital Aristide Le Dantec from January 1993 to December 2002. All patients with systemic lupus erythematosus according to the ACR criteria were included. Those who didn't meet ACR criteria were excluded. we included 74 patients; their mean age was 32 years and the sex ratio 0.1 (male to female). At the entry general symptoms were constants, and cutaneous signs were found in 96% of cases, joints signs in 58.1% and renal sign in 56.8%. Haematological and immunologic abnormalities were nearly constant. All the patients received corticosteroids and in 35.71% they had in addition immunosuppressive drugs. Shorts term evolution was satisfactory. At the medium term 27.02% of the patients were lost and 10.81% of them died. currents aspects of systemic lupus erythematosus in Dakar are improved by the early diagnosis when the disease is pauci-symptomatic and by the use immunosuppressive drugs in association with corticosteroids.

An unusual case of crescentic lupus nephritis presenting with normal renal function.

PubMed

Manohar, Sandhya; Subramanian, Chamundeswari; Lakshmi, Kameswari

2015-11-01

Lupus nephritis is a life-threatening manifestation of systemic lupus erythematosus (SLE). This is commonly suspected when lupus patients present with elevated serum creatinine levels. But it is important to be aware that even patients with advanced disease in the kidney from SLE can have normal renal function, thus requiring a high index of suspicion. We present the case of a patient who presented with nonspecific musculoskeletal symptoms and was diagnosed with SLE. He also had nephrotic range proteinuria but his serum creatinine was normal. A renal biopsy revealed diffuse proliferative crescentic lupus nephritis. We have reviewed the literature for correlation between crescents; a sign of severe glomerular damage and creatinine levels.

A CD8 T Cell/Indoleamine 2,3-Dioxygenase Axis Is Required for Mesenchymal Stem Cell Suppression of Human Systemic Lupus Erythematosus

PubMed Central

Wang, Dandan; Feng, Xuebing; Lu, Lin; Konkel, Joanne E; Zhang, Huayong; Chen, Zhiyong; Li, Xia; Gao, Xiang; Lu, Liwei; Shi, Songtao; Chen, Wanjun; Sun, Lingyun

2014-01-01

Objective Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients. Methods The effects of allogeneic umbilical cord–derived MSCs (UC-MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real-time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC–mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC-MSC transplantation. Results Allogeneic UC-MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3-dioxygenase (IDO). We further found that interferon-γ (IFNγ), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK-2/STAT signaling pathways. Intriguingly, bone marrow–derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFNγ and allogeneic CD8+ T cell stimulation. After allogeneic UC-MSC transplantation, serum IDO activity increased in lupus patients. Conclusion We found a previously unrecognized CD8+ T cell/IFNγ/IDO axis that mediates the therapeutic effects of allogeneic MSCs in lupus patients. PMID:24756936

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus

PubMed Central

Sanchez, Elena; Nadig, Ajay; Richardson, Bruce C; Freedman, Barry I; Kaufman, Kenneth M; Kelly, Jennifer A; Niewold, Timothy B; Kamen, Diane L; Gilkeson, Gary S; Ziegler, Julie T; Langefeld, Carl D; Alarcón, Graciela S; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Brown, Elizabeth E; Kimberly, Robert P; Reveille, John D; Vilá, Luis M; Merrill, Joan T; Anaya, Juan-Manuel; James, Judith A; Pons-Estel, Bernardo A; Martin, Javier; Park, So-Yeon; Bang, So-Young; Bae, Sang-Cheol; Moser, Kathy L; Vyse, Timothy J; Criswell, Lindsey A; Gaffney, Patrick M; Tsao, Betty P; Jacob, Chaim O; Harley, John B; Alarcón-Riquelme, Marta E; Sawalha, Amr H

2011-01-01

Objective Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods 4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0×10−6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of <0.05 and pass the significance threshold using Bonferroni correction for multiple testing. Conclusion Significant associations were found between lupus clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future. PMID:21719445

Disruption of Pathogenic Cellular Networks by IL-21 Blockade Leads to Disease Amelioration in Murine Lupus.

PubMed

Choi, Jin-Young; Seth, Abhinav; Kashgarian, Michael; Terrillon, Sonia; Fung, Emma; Huang, Lili; Wang, Li Chun; Craft, Joe

2017-04-01

Systemic lupus erythematosus (lupus) is characterized by autoantibody-mediated organ injury. Follicular Th (Tfh) cells orchestrate physiological germinal center (GC) B cell responses, whereas in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell-derived autoantibody production. IL-21, a Tfh cell-derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as systemic lupus erythematosus. We used blockade of IL-21 to dissect the mechanisms by which this cytokine promotes autoimmunity in murine lupus. Treatment of lupus-prone B6. Sle1.Yaa mice with an anti-IL-21 blocking Ab reduced titers of autoantibodies, delayed progression of glomerulonephritis and diminished renal-infiltrating Tfh and Th1 cells, and improved overall survival. Therapy inhibited excessive accumulation of Tfh cells coexpressing IL-21 and IFN-γ, and suppressed their production of the latter cytokine, albeit while not affecting their frequency. Anti-IL-21 treatment also led to a reduction in GC B cells, CD138 hi plasmablasts, IFN-γ-dependent IgG2c production, and autoantibodies, indicating that Tfh cell-derived IL-21 is critical for pathological B cell cues in lupus. Normalization of GC responses was, in part, caused by uncoupling of Tfh-B cell interactions, as evidenced by reduced expression of CD40L on Tfh cells and reduced B cell proliferation in treated mice. Our work provides mechanistic insight into the contribution of IL-21 to the pathogenesis of murine lupus, while revealing the importance of T-B cellular cross-talk in mediating autoimmunity, demonstrating that its interruption impacts both cell types leading to disease amelioration. Copyright © 2017 by The American Association of Immunologists, Inc.

The impact of obesity in systemic lupus erythematosus on disease parameters, quality of life, functional capacity and the risk of atherosclerosis.

PubMed

Rizk, Amal; Gheita, Tamer A; Nassef, Sahar; Abdallah, Abeer

2012-06-01

To study the effect of obesity on the quality of life (QoL), functional capacity and the risk of carotid atherosclerotic plaque formation in systemic lupus erythematosus (SLE) patients and to correlate the findings with disease parameters, activity and damage. Sixty SLE patients were clinically examined, investigated and their carotid intima media thickness (IMT) measured by ultrasonography. Assessment of the QoL, Health Assessment Questionnaire(HAQ-II), fatigue severity scale (FSS), the disease activity using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the damage by Systemic Lupus International Collaboration Clinics (SLICC)/American College of Rheumatology (ACR) damage index were performed on all patients. Patients were grouped according to their body mass index (BMI). The mean age of the patients was 28.55 8.08 years, disease duration 6.49 5.18 years with a female : male ratio of 5.67 : 1. There was a significant association of increased BMI with lupus nephritis and hypertension. In obese SLE patients, there was a significant decrease in QoL and functional capacity and obvious dyslipidemia. The IMT was increased and significantly correlated with waist circumference. In SLE patients, there is an association of BMI with dyslipidemia and decreased QoL. Its role in disease activity is not clear and obesity was associated with SLE damage accrual, especially lupus nephritis among other risk factors, including age, disease duration and increased steroid use. Increased waist circumference increases the risk of atherosclerosis.

Treatment of severe lupus nephritis: the new horizon.

PubMed

Chan, Tak Mao

2015-01-01

Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

The role of antimalarial agents in the treatment of SLE and lupus nephritis.

PubMed

Lee, Senq-J; Silverman, Earl; Bargman, Joanne M

2011-10-18

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that affects various organs. Lupus nephritis is one of the most common, and most important, serious manifestations of SLE. Antimalarial agents are part of the immunomodulatory regimen used to treat patients with SLE; however, their role in the treatment of patients with lupus nephritis in particular is less well recognized, especially by nephrologists. Not all antimalarial agents have been used in the treatment of lupus; this Review will focus on studies using chloroquine and hydroxychloroquine. In addition, this Review will briefly describe the history of antimalarial drug use in patients with SLE, the theorized mechanisms of action of the agents chloroquine and hydroxychloroquine, their efficacy in patients with SLE and those with lupus nephritis, their use in pregnancy, and potential adverse effects. The Review will also cover the latest recommendations regarding monitoring for hydroxychloroquine-associated or chloroquine-associated retinopathy. Overall, antimalarial drugs have numerous beneficial effects in patients with SLE and lupus nephritis, and have a good safety profile.

The needs of persons with lupus and health care providers: a qualitative study aimed toward the development of the Lupus Interactive Navigator™.

PubMed

Neville, C; Da Costa, D; Mill, C; Rochon, M; Aviña-Zubieta, J A; Pineau, C A; Eng, D; Fortin, P R

2014-02-01

Systemic lupus erythematosus is an inflammatory autoimmune disease associated with high morbidity and unacceptable mortality. A major challenge for persons with lupus is coping with their illness and complex care. Our objective was to identify the informational and resource needs of persons with lupus, rheumatologists, and allied health professionals treating lupus. Our findings will be applied toward the development of an innovative web-based technology, the Lupus Interactive Navigator (LIN™), to facilitate and support engagement and self-management for persons with lupus. Eight focus groups were conducted: four groups of persons with lupus (n=29), three groups of rheumatologists (n=20), and one group of allied health professionals (n=8). The groups were held in British Columbia, Ontario, and Quebec. All sessions were audio-recorded and transcribed verbatim. Qualitative analysis was performed using grounded theory. The transcripts were reviewed independently and coded by the moderator and co-moderator using 1) qualitative data analysis software developed by Provalis Research, Montreal, Canada, and 2) manual coding. Four main themes emerged: 1) specific information and resource needs; 2) barriers to engagement in health care; 3) facilitators of engagement in health care; and 4) tools identified as helpful for the self-management of lupus. These findings will help guide the scope of LIN™ with relevant information topics and specific tools that will be most helpful to the diverse needs of persons with lupus and their health care providers.

Primary prevention of cardiovascular disease in patients with systemic lupus erythematosus: case series and literature review.

PubMed

Fasano, S; Margiotta, D P; Navarini, L; Pierro, L; Pantano, I; Riccardi, A; Afeltra, A; Valentini, G

2017-12-01

Background Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. Low-dose aspirin, hydroxychloroquine and statins have been suggested to play a prophylactic role of cardiovascular events. This study is devoted to reviewing the literature on the topic and assessing the effects of these drugs in preventing a first cardiovascular event in a two-centre Italian series. Methods A PubMed search on cardiovascular prevention in systemic lupus erythematosus was performed. Moreover, systemic lupus erythematosus patients admitted to two centres from 2000-2015, who at admission had not experienced any cardiovascular event, were investigated. Aspirin, hydroxychloroquine and statin use, and the occurrence of any cardiovascular event, were recorded at each visit. Kaplan-Meier and Cox regression analyses were performed to evaluate the role of traditional, disease-related cardiovascular risk factors and of each of the three drugs in the occurrence of new cardiovascular events. Results The literature search produced conflicting results. Two hundred and ninety-one systemic lupus erythematosus patients were included in the study and followed for a median of eight years. During follow-up, 16 cardiovascular events occurred. At multivariate analysis, taking aspirin (hazard ratio: 0.24) and hydroxychloroquine for more than five years (hazard ratio: 0.27) reduced, while antiphospholipid antibody positivity (hazard ratio: 4.32) increased, the risk of a first cardiovascular event. No effect of statins emerged. Conclusion Our study confirms an additive role of aspirin and hydroxychloroquine in the primary prophylaxis of cardiovascular events in Italian patients with systemic lupus erythematosus. The lack of any detected effect in previous reports may depend on the design of studies and their short follow-up period.

Organ damage accrual and distribution in systemic lupus erythematosus patients followed-up for more than 10 years.

PubMed

Taraborelli, M; Cavazzana, I; Martinazzi, N; Lazzaroni, M Grazia; Fredi, M; Andreoli, L; Franceschini, F; Tincani, A

2017-10-01

Objective The aim of this study was to determine the prevalence, predictors and progression of organ damage in a monocentric cohort of systemic lupus erythematosus patients with a long follow-up. Organ damage was assessed by the Systemic Lupus International Collaborating Clinics Damage Index one year after diagnosis and every five years. Disease activity was measured by the systemic lupus erythematosus disease activity index (SLEDAI)-2K at the beginning of the follow-up. Univariate and multivariable analyses were used to detect items associated with damage. A total of 511 systemic lupus erythematosus patients (92% females, 95% Caucasian), prospectively followed from 1972 to 2014, were included. Results After a mean disease duration of 16 years (SD: 9.5) and a mean follow-up of 12.9 years (SD: 8.8), 354 patients (69.3%) had accrued some damage: 49.7% developed mild/moderate damage, while 19.5% showed severe damage. Damage was evident in 40% of 511 patients one year after diagnosis, and its prevalence linearly increased over time. Longer disease duration, higher SLEDAI, severe Raynaud's, chronic alopecia and cerebral ischaemia were significantly associated with organ damage. No associations between damage and autoantibodies, including anti-dsDNA, anti-Sm or antiphospholipid antibodies, were observed. Anyway, antiphospholipid syndrome and anticardiolipin antibodies predicted the development of neuropsychiatric damage. The ocular, musculoskeletal and neuropsychiatric systems were the most frequently damaged organs, with a linear increase during follow-up. Conclusion A high rate of moderate and severe damage has been detected early in a wide cohort of young lupus patients, with a linear trend of increase over time. Disease activity and long duration of disease predict damage, while antiphospholipid antibodies play a role in determining neuropsychiatric damage.

What Social Workers in Health Care Should Know about Lupus: A Structural Equation Model

ERIC Educational Resources Information Center

Auerbach, Charles; Beckerman, Nancy L.

2011-01-01

This article reports on findings from a cross-sectional study (N = 378) of patients living with systemic lupus erythematosus (SLE). The purpose of this study was to identify and clarify the unique psychosocial challenges for those living with lupus. The specific analysis will help to develop a model to determine how different factors influence SLE…

Degos' disease: a distinctive pattern of disease, chiefly of lupus erythematosus, and not a specific disease per se.

PubMed

Ball, Elizabeth; Newburger, Amy; Ackerman, A Bernard

2003-08-01

Degos' disease, known confusingly as malignant strophic papularis, is an uncommon condition of unknown cause characterized by distinctive infarctive lesions in the skin, gastrointestinal tract, and central nervous system; the lesions at the two latter sites often result in death. We deem Degos' disease to be analogous to lupus erythematosus in the sense that each is fundamentally a systemic pathologic process involving several organs, among them the skin, but, moreover, we regard Degos' disease, in most instances, to be an actual manifestation of lupus erythematosus. Histopathologically, the findings in sections of tissue of skin lesions of Degos' disease are indistinguishable from those of one expression of cutaneous lupus erythematosus; immunopathologically, some patients with morphologic findings stereotypical of Degos' disease display signs characteristic of lupus erythematosus. For these reasons, we consider Degos' disease to be a distinctive pattern of disease, rather than a specific disease per se, just as are erythema multiforme, erythema nodosum, leukocytoclastic vasculitis, Sweet's syndrome, and pyoderma gangrenosum, to name but five of scores of them. The singular pattern that is designated Degos' disease usually is an expression of lupus erythematosus, but, episodically, of conditions like dermatomyositis and rheumatoid arthritis.

Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus.

PubMed

McGrath, H

2017-10-01

Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is "autoimmunity." Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these mechanisms reduces levels of anticardiolipin antibodies and protects during lupus pregnancy. Capping all of this is that UV-A1 irradiation is an essentially innocuous, highly manageable, and comfortable therapeutic agency.

Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus

PubMed Central

2017-01-01

Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is “autoimmunity.” Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these mechanisms reduces levels of anticardiolipin antibodies and protects during lupus pregnancy. Capping all of this is that UV-A1 irradiation is an essentially innocuous, highly manageable, and comfortable therapeutic agency. PMID:28480786

Cigarette smoking and cutaneous damage in systemic lupus erythematosus.

PubMed

Turchin, Irina; Bernatsky, Sasha; Clarke, Ann E; St-Pierre, Yvan; Pineau, Christian A

2009-12-01

To evaluate the association between cigarette smoking and cutaneous damage in systemic lupus erythematosus (SLE). Our study was performed in SLE clinic registry cohort patients, all of whom fulfilled revised American College of Rheumatology criteria for SLE; patients are followed prospectively with annual assessments that include collection of demographic variables, smoking history, disease activity (SLE Disease Activity Index version 2000, SLEDAI-2K), medications, and damage scores (Systemic Lupus International Collaborating Clinics/ACR Damage Index). Cumulative cutaneous damage scores were used for the primary analyses. Logistic and logit regression models were performed to examine potential associations between current smoking and cutaneous damage, controlling for age, sex, race, lupus disease duration, antimalarial or immunosuppressant use, and anti-DNA and anti-SSA antibody status. Of our sample (N = 276), 92% were women and 73.7% were Caucasian; the mean age was 45.1 years, mean disease duration 13.5 years, and 17.5% were current smokers. In the regression analyses, current cigarette smoking was associated with total cutaneous damage (OR 2.73, 95% CI 1.10, 6.81) and with scarring (OR 4.70, 95 CI 1.04, 21.2). In additional analyses, current smoking was also associated with active lupus rash (OR 6.18, 95% CI 1.63, 23.3). Current cigarette smoking may be associated with cutaneous damage and active lupus rash in SLE, suggesting another reason to emphasize smoking cessation in patients with SLE.

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

PubMed

Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

2005-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Pregnancy Outcomes in Chinese Patients with Systemic Lupus Erythematosus (SLE): A Retrospective Study of 109 Pregnancies

PubMed Central

Ku, Ming; Guo, Shuiming; Shang, Weifeng; Li, Qing; Zeng, Rui; Han, Min; Ge, Shuwang; Xu, Gang

2016-01-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that primarily affects women during their reproductive years. The interaction between SLE and pregnancy remains debated. The objective of this study was to analyze the fetal and maternal outcomes of Chinese women with SLE. A total of 109 pregnancies in 83 SLE patients from June 2004 to June 2014 at a tertiary university hospital were reviewed retrospectively. Patients’ characteristics, clinical and laboratory data during pregnancy were obtained from electronic medical records. After exclusion of elective abortions, the live birth rate was 61.5%. Significantly, APS (antiphospholipid syndrome), disease activity, hypertension, hypocomplementemia, thrombocytopenia, and anemia during pregnancy were more commonly observed in fetal loss pregnancies than in live birth pregnancies. Compared to the 64 women with a history of SLE, 19 women with new-onset lupus during pregnancy had worse pregnancy outcome. Furthermore, the 64 patients with a history of SLE were divided into lupus nephritis group and SLE group (non-renal involvement). We found that the lupus nephritis group had worse maternal outcome than the SLE group. We conclude that new-onset lupus during pregnancy predicts both adverse maternal and fetal outcomes, while a history of lupus nephritis predicts adverse maternal outcomes. It is essential to provide SLE women with progestational counseling and regular multispecialty care during pregnancy. PMID:27442513

B-cell-depleting Therapy in Systemic Lupus Erythematosus

PubMed Central

Ramos-Casals, Manuel; Sanz, Iñaki; Bosch, Xavier; Stone, John H.; Khamashta, Munther A.

2014-01-01

The emergence of a new class of agents (B-cell-depleting therapies) has opened a new era in the therapeutic approach to systemic lupus erythematosus, with belimumab being the first drug licensed for use in systemic lupus erythematosus in more than 50 years. Four agents deserve specific mention: rituximab, ocrelizumab, epratuzumab, and belimumab. Controlled trials have shown negative results for rituximab, promising results for epratuzumab, and positive results for belimumab. Despite these negative results, rituximab is the most-used agent in patients who do not respond or are intolerant to standard therapy and those with life-threatening presentations. B-cell-depleting agents should not be used in patients with mild disease and should be tailored according to individual patient characteristics, including ethnicity, organ involvement, and the immunological profile. Forthcoming studies of B-cell-directed strategies, particularly data from investigations of off-label rituximab use and postmarketing studies of belimumab, will provide new insights into the utility of these treatments in the routine management of patients with systemic lupus erythematosus. PMID:22444096

[Prevention of systemic lupus erythematosus in children born to mothers treated for this disease].

PubMed

Kardaszewicz, E; Machalski, M; Woszczyk, D; Woszczyk, M; Harbut-Gryłka, A

Genetic predisposition and environmental factors (physical, chemical, hormonal and drugs inducing collagen-like syndrome) play an important role in the pathogenesis of the systemic lupus erythematosus. Elimination of these factors from the environment of the genetically predisposed individuals may prevent part of them against the disease. Basing on the above assumption, a chart of prophylaxis has been constructed and distributed among the mothers with the systemic lupus erythematosus, recommending prophylactic measures in both mothers and children. Within 1977-1987, 50 children were examined from time to time. Basic laboratory tests, phenomenon LE, antinuclear antibodies and antibodies anti-DNA have been determined. Transient presence of antinuclear antibodies was seen in 23 children. A tendency to an increase in the antibody titre was observed in girls of this group whereas a decrease in the titre was noted in the boys with the time lapse. Systemic lupus erythematosus prophylaxis in both mothers and children is uncomplicated and favourable for children. Regular determination of antibodies enables early diagnosis of the disease.

Pseudo-pseudo Meigs' syndrome in a patient with systemic lupus erythematosus.

PubMed

Dalvi, S R; Yildirim, R; Santoriello, D; Belmont, H M

2012-11-01

Pseudo-pseudo Meigs' syndrome (PPMS) is a rare manifestation of patients with systemic lupus erythematosus (SLE), defined by the presence of ascites, pleural effusions and an elevated CA-125 level. We describe a patient with longstanding lupus who presented with localized lymphadenopathy and subsequently developed massive chylous ascites with marked hypoalbuminemia. A brief historical overview of Meigs' syndrome and related entities is presented, along with a discussion of the differential diagnosis of hypoalbuminemia and ascites in an SLE patient. In addition, we speculate on the optimal therapeutic intervention in such a patient.

Genome-wide transcriptional profiling data from chronic cutaneous lupus erythematosus (CCLE) peripheral blood.

PubMed

Dey-Rao, R; Sinha, A A

2015-03-01

The disease Lupus erythematosus (LE), exhibits a variety of clinical manifestations with potentially wide-ranging multi-organ damage to joints, tendons, kidney, lung, heart, blood vessels, central nervous system and skin [1,2] Systemic changes are likely to trigger organ specific manifestation of the disease. Here, we provide the data examined to address the gap in knowledge regarding causes and mechanisms contributing to the autoimmune attack on skin in chronic cutaneous lupus erythematosus (CCLE). The raw gene expression data files (CEL files) are provided with this article [3].

Severely Crusted Cheilitis as an Initial Presentation of Systemic Lupus Erythematosus.

PubMed

Chan, Wai Man Mandy; Pang, Shiu Ming; Ng, See Ket

2017-01-01

Lupus erythematosus (LE) is an autoimmune disease which may initially present solely with lip lesions. Due to a wide spectrum of presentation, these features may initially be misdiagnosed as other oral diseases such as lichen planus, erythema multiforme (EM), and actinic cheilitis, leading to a delay in diagnosis and treatment. We discuss a case of severely crusted cheilitis which was initially diagnosed as EM, with subsequent development of subacute cutaneous LE, and progression to systemic LE. We will discuss the clinical and histological features of lupus cheilitis.

Guillian-Barre syndrome as the initial presentation of systemic lupus erythematosus--case report and review of literature.

PubMed

Nadri, Quaid; Althaf, Mohammed Mahdi

2015-01-01

A number of neurological entities have been associated with systemic lupus erythematosus (SLE). Gullian-Barre syndrome (GBS) as a presenting feature of SLE remains uncommon with just 9 cases reported in the last half-century with the first case reported in 19641-9 (Table 1). We report a young female presenting with GBS in whom SLE and WHO class V lupus nephritis (LN) was subsequently diagnosed. The neurological symptoms partially responded to pulse methylprednisone, intravenous immunoglobulin (IVIG) and plasmapheresis.

Genomics of Systemic Lupus Erythematosus: Insights Gained by Studying Monogenic Young-Onset Systemic Lupus Erythematosus.

PubMed

Hiraki, Linda T; Silverman, Earl D

2017-08-01

Systemic lupus erythematosus (SLE) is a systemic, autoimmune, multisystem disease with a heterogeneous clinical phenotype. Genome-wide association studies have identified multiple susceptibility loci, but these explain a fraction of the estimated heritability. This is partly because within the broad spectrum of SLE are monogenic diseases that tend to cluster in patients with young age of onset, and in families. This article highlights insights into the pathogenesis of SLE provided by these monogenic diseases. It examines genetic causes of complement deficiency, abnormal interferon production, and abnormalities of tolerance, resulting in monogenic SLE with overlapping clinical features, autoantibodies, and shared inflammatory pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Perspectives on Lupus Genetics: Advances and Opportunities

PubMed Central

James, Judith A.

2014-01-01

Synopsis In recent years, genome wide association studies have led to an explosion in the identification of regions containing confirmed genetic risk variants within complex human diseases, for example in systemic lupus erythematosus (SLE). Many of these strongest SLE genetic associations can be divided into groups based upon their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination (a process of marking proteins for degradation), DNA degradation, innate immunity, cellular immunity (B cell, T cell, neutrophil, monocytes), lymphocyte development, and antigen presentation. Recent advances have also demonstrated several genetic associations with SLE subphenotypes and subcriteria, such as autoantibody production, lupus nephritis, serositis, and arthritis. Despite the broad range of lupus genetic studies to date, many areas for further exploration remain to move lupus genetic studies toward clinically informative endpoints, such as identifying individuals at the greatest risk of end-organ damage, early mortality or poor response to a specific therapeutic regimen. PMID:25034154

Anti-nucleosome antibodies as a disease marker in systemic lupus erythematosus and its correlation with disease activity and other autoantibodies.

PubMed

Pradhan, Vandana D; Patwardhan, Manisha M; Ghosh, Kanjaksha

2010-01-01

Detection of anti-nucleosome antibodies (anti-nuc) in patients with systemic lupus erythematosus (SLE) has been well established and it is claimed that their presence is associated with disease activity. The aim of this study is to evaluate the incidence of anti-nuc antibodies and to correlate them with disease activity and its association with other autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), as well as autoantibodies to histone subfractions like H1, (H2A-H4) complex, H2B, and H3. This cross-sectional study included 100 SLE patients referred from the Rheumatology, Dermatology, and Nephrology Departments. SLE disease activity was evaluated by using SLE-Disease Activity Index (SLEDAI) score. A patient was defined as having active SLE when the SLEDAI score was more than 5.0. Fifty normal controls were also tested as a healthy control group. Anti-nuc antibodies, anti-dsDNA, and AHA were tested by Enzyme-Linked Immunosorbent Assay (ELISA) and ANA was detected by an indirect immunofluorescence test. All patients studied were in an active stage of disease and were untreated, of which 44 patients had renal biopsy-proven kidney involvement, which was categorized as lupus nephritis (LN) and 56 patients did not show any renal manifestations (SLE without LN). Anti-nuc antibodies were positive in 88%, anti-dsDNA in 80%, and AHA in 38% of the cases. ANA was positive in all SLE patients studied. None of the normal controls was found to be positive for these antibodies. Although a slightly higher incidence of autoantibodies were noted in LN, there was no statistical difference noted between LN and SLE without LN groups for anti-nuc and anti-dsDNA antibodies (p > 0.05). A higher incidence of autoantibodies to ANA specificities were noted in anti-nuc positive cases, but there was no statistical difference between anti-nuc positive and anti-nuc negative cases for ANA specificities among LN and SLE without nephritis groups (p > 0.05). Anti-nuc antibody detection could be a better tool for the diagnosis of SLE. Although there was no significant difference in LN and SLE without LN groups, this study suggests that anti-nuc detection can be useful as an additional disease activity marker to other laboratory tests.

Chronic Pericarditis

MedlinePlus

... that causes acute pericarditis , such as rheumatoid arthritis, systemic lupus erythematosus (lupus), a previous injury, or a ... is normal, doctors take a wait-and-see approach. If the disorder causes symptoms or if an ...

A Comprehensive Rehabilitation Approach in a Patient With Serious Neuropsychiatric Systemic Lupus Erythematosus.

PubMed

Ko, Yong Jae; Lee, Yang Gyun; Park, Ji Woong; Ahn, Sung Ho; Kwak, Jin Myoung; Choi, Yoon-Hee

2016-08-01

Neuropsychiatric systemic lupus erythematosus (NPSLE) involves the central and peripheral nervous system in patients with systemic lupus erythematosus (SLE). It is essential to specify the problems faced by patients with NPSLE because it causes diverse disabilities and impairs quality of life. After performing a comprehensive evaluation, tailored management should be provided for the patient's specific problems. We report here the case of a 30-year-old female with SLE who experienced serious neuropsychiatric symptoms cerebral infarction followed by posterior reversible encephalopathy syndrome and peripheral polyneuropathy. We systemically assessed the patient using the International Classification of Functioning, Disability and Health model as a clinical problem-solving tool and provided comprehensive rehabilitation by focusing on her problems.

Integrative medicine for managing the symptoms of lupus nephritis

PubMed Central

Choi, Tae-Young; Jun, Ji Hee; Lee, Myeong Soo

2018-01-01

Abstract Background: Integrative medicine is claimed to improve symptoms of lupus nephritis. No systematic reviews have been performed for the application of integrative medicine for lupus nephritis on patients with systemic lupus erythematosus (SLE). Thus, this review will aim to evaluate the current evidence on the efficacy of integrative medicine for the management of lupus nephritis in patients with SLE. Methods and analyses: The following electronic databases will be searched for studies published from their dates of inception February 2018: Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as 6 Korean medical databases (Korea Med, the Oriental Medicine Advanced Search Integrated System [OASIS], DBpia, the Korean Medical Database [KM base], the Research Information Service System [RISS], and the Korean Studies Information Services System [KISS]), and 1 Chinese medical database (the China National Knowledge Infrastructure [CNKI]). Study selection, data extraction, and assessment will be performed independently by 2 researchers. The risk of bias (ROB) will be assessed using the Cochrane ROB tool. Dissemination: This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide healthcare practice and policy. Trial registration number: PROSPERO 2018 CRD42018085205 PMID:29595669

Numerous Fusiform and Saccular Cerebral Aneurysms in Central Nervous System Lupus Presenting with Ischemic Stroke.

PubMed

Majidi, Shahram; Leon Guerrero, Christopher R; Gandhy, Shreya; Burger, Kathleen M; Sigounas, Dimitri

2017-07-01

Central nervous system (CNS) involvement occurs in up to 50% of patients with systemic lupus erythematosus (SLE). Cerebral aneurysm formation is a rare complication of CNS lupus. The majority of these patients present with subarachnoid hemorrhage. We report a patient with an active SLE flare who presented with a recurrent ischemic stroke and was found to have numerous unruptured fusiform and saccular aneurysms in multiple vascular territories. He was treated with high-dose steroid and rituximab along with aspirin and blood pressure control for stroke prevention. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Infection in systemic lupus erythematosus: friend or foe?

PubMed Central

Francis, Lisa; Perl, Andras

2010-01-01

Infectious agents have long been implicated in the pathogenesis of systemic lupus erythematosus. Common viruses, such as the Epstein-Barr virus, transfusion transmitted virus, parvovirus and cytomegalovirus, have an increased prevalence in patients with systemic lupus erythematosus. They may contribute to disease pathogenesis through triggering autoimmunity via structural or functional molecular mimicry, encoding proteins that induce cross-reactive immune responses to self antigens or modulate antigen processing, activation, or apoptosis of B and T cells, macrophages or dendritic cells. Alternatively, some infectious agents, such as malaria, Toxoplasma gondii and Helicobacter pylori, may have a protective effect. Vaccinations may play dual roles by protecting against friend and foe alike. PMID:20209114

Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice.

PubMed

Menke, Julia; Hsu, Mei-Yu; Byrne, Katelyn T; Lucas, Julie A; Rabacal, Whitney A; Croker, Byron P; Zong, Xiao-Hua; Stanley, E Richard; Kelley, Vicki R

2008-11-15

Sunlight (UVB) triggers cutaneous lupus erythematosus (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mø)-mediated mechanism in MRL-Fas(lpr) mice. By constructing mutant MRL-Fas(lpr) strains expressing varying levels of CSF-1 (high, intermediate, none), and use of an ex vivo gene transfer to deliver CSF-1 intradermally, we determined that CSF-1 induces CLE in lupus-susceptible MRL-Fas(lpr) mice, but not in lupus-resistant BALB/c mice. UVB incites an increase in Møs, apoptosis in the skin, and CLE in MRL-Fas(lpr), but not in CSF-1-deficient MRL-Fas(lpr) mice. Furthermore, UVB did not induce CLE in BALB/c mice. Probing further, UVB stimulates CSF-1 expression by keratinocytes leading to recruitment and activation of Møs that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mø-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL-Fas(lpr) but not lupus-resistant BALB/c mice. Taken together, CSF-1 is envisioned as the match and lupus susceptibility as the tinder leading to CLE.

Infection of Female BWF1 Lupus Mice with Malaria Parasite Attenuates B Cell Autoreactivity by Modulating the CXCL12/CXCR4 Axis and Its Downstream Signals PI3K/AKT, NFκB and ERK

PubMed Central

Badr, Gamal; Sayed, Ayat; Abdel-Maksoud, Mostafa A.; Mohamed, Amany O.; El-Amir, Azza; Abdel-Ghaffar, Fathy A.; Al-Quraishy, Saleh; Mahmoud, Mohamed H.

2015-01-01

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by abnormal autoreactivity in B cells. Lymphocytes and their soluble mediators contribute to the disease pathogenesis. We recently demonstrated that infecting lupus mice with malaria confers protection against lupus nephritis by attenuating oxidative stress in both liver and kidney tissues. In the current study, we further investigated B cell autoreactivity in female BWF1 lupus mice after infection with either live or gamma-irradiated malaria, using ELISA, flow cytometry and Western blot analysis. The lupus mice exhibited a significant elevation in plasma levels of IL-4, IL-6, IL-7, IL-12, IL-17, IFN-α, IFN-γ, TGF-β, BAFF and APRIL and a marked elevation of IgG2a, IgG3 and ant-dsDNA autoantibodies compared with normal healthy mice. Infecting lupus mice with live but not gamma-irradiated malaria parasite partially and significantly restored the levels of the soluble mediators that contribute to the progression of lupus. Furthermore, the B cells of lupus mice exhibited an increased proliferative capacity; aberrant overexpression of the chemokine receptor CXCR4; and a marked elevation in responsiveness to their cognate ligand (CXCL12) via aberrant activation of the PI3K/AKT, NFκB and ERK signaling pathways. Interestingly, infecting lupus mice with live but not gamma-irradiated malaria parasite restored a normal proliferative capacity, surface expression of CXCR4 and B cell response to CXCL-12. Taken together, our data present interesting findings that clarify, for the first time, the molecular mechanisms of how infection of lupus mice with malaria parasite controls B cell autoreactivity and thus confers protection against lupus severity. PMID:25909640

Infection of Female BWF1 Lupus Mice with Malaria Parasite Attenuates B Cell Autoreactivity by Modulating the CXCL12/CXCR4 Axis and Its Downstream Signals PI3K/AKT, NFκB and ERK.

PubMed

Badr, Gamal; Sayed, Ayat; Abdel-Maksoud, Mostafa A; Mohamed, Amany O; El-Amir, Azza; Abdel-Ghaffar, Fathy A; Al-Quraishy, Saleh; Mahmoud, Mohamed H

2015-01-01

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by abnormal autoreactivity in B cells. Lymphocytes and their soluble mediators contribute to the disease pathogenesis. We recently demonstrated that infecting lupus mice with malaria confers protection against lupus nephritis by attenuating oxidative stress in both liver and kidney tissues. In the current study, we further investigated B cell autoreactivity in female BWF1 lupus mice after infection with either live or gamma-irradiated malaria, using ELISA, flow cytometry and Western blot analysis. The lupus mice exhibited a significant elevation in plasma levels of IL-4, IL-6, IL-7, IL-12, IL-17, IFN-α, IFN-γ, TGF-β, BAFF and APRIL and a marked elevation of IgG2a, IgG3 and ant-dsDNA autoantibodies compared with normal healthy mice. Infecting lupus mice with live but not gamma-irradiated malaria parasite partially and significantly restored the levels of the soluble mediators that contribute to the progression of lupus. Furthermore, the B cells of lupus mice exhibited an increased proliferative capacity; aberrant overexpression of the chemokine receptor CXCR4; and a marked elevation in responsiveness to their cognate ligand (CXCL12) via aberrant activation of the PI3K/AKT, NFκB and ERK signaling pathways. Interestingly, infecting lupus mice with live but not gamma-irradiated malaria parasite restored a normal proliferative capacity, surface expression of CXCR4 and B cell response to CXCL-12. Taken together, our data present interesting findings that clarify, for the first time, the molecular mechanisms of how infection of lupus mice with malaria parasite controls B cell autoreactivity and thus confers protection against lupus severity.

Psychosis, central hyperventilation and inappropriate secretion of antidiuretic hormone in systemic lupus erythematosus

PubMed Central

Decaux, G.; Unger, J.; Marneffe, C.

1981-01-01

A case of systemic lupus erythematosus with reversible psychosis and hyperventilation related to hyponatraemia secondary to a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is presented. The SIADH was treated successfully by oral urea for more than 8 months. PMID:7339606

Multicenter study to assess presenteeism in systemic lupus erythematosus and its relationship with clinical and sociodemographic features.

PubMed

Cosatti, M A; Muñoz, S; Alba, P; Helling, C A; Roverano, S; Sarano, J; Malm-Green, S; Danielsen, M; Medina Bornachera, D; Alvarez, A; Eimon, A; Pendón, G; Mayer, M; Marin, J; Catoggio, C; Pisoni, C N

2018-01-01

Objective The aim of this study was to measure presenteeism (productivity impairment while the patient is at work) and the related risk factors in patients with systemic lupus erythematosus (SLE) from Argentina. Methods A total of 130 consecutive (1997 American College of Rheumatology (ACR) criteria) working patients with SLE were assessed using a standardized data collection form. Sociodemographic, disease and work-related variables were collected. The Work Productivity and Activity Impairment (WPAI) questionnaire was performed. Results Overall, 130 patients were included in the analysis; 91% were women, and the mean age was 39 years (range 19-77). A total of 43% were White, 43% Mestizo and 13% Amerindian. Overall, 38% were single and 38% were married. A total of 75% had more than 12 years of formal education. The median disease duration was 7 years (interquartile range 25-75 (IQR) 4-13). Median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 0 (IQR 0-2), and median Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC-SDI) score was 0 (IQR 0-1). Lupus quality of life (LupusQoL) domains scores were: physical health 87 (IQR 70-96), emotional health 78 (IQR 54-91), burden to others 75 (IQR 50-92), intimate relationships 87 (IQR 50-100), and body image 85 (IQR 70-100). Absenteeism was 8%, presenteeism was 19%, and overall work impairment (absenteeism + presenteeism) was 26%. In the multiple regression analysis, considering presenteeism as dependent variable, (adjusting by age, disease duration, >12 years of education, Non-white race, Visual Analogue Scale (VAS) pain, VAS fatigue, SLICC-SDI, LupusQoL, physical and emotional domains), we found that SLICC-SDI (odds ratio (OR) 1.68, confidence interval (CI) 1-2.7) and Non-white race (OR 3.27, CI 1.04-10) were related to presenteeism and >12 years of education (OR 0.30, CI 0.09-0.98) and higher scores of LupusQoL emotional health domain (OR 0.95, CI 0.92-0.98) were protective. Conclusions organ damage and Non-white race were significantly associated with presenteeism while >12 years of education and higher scores of LupusQoL emotional health domain were protective.

Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

PubMed

Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E

2015-05-01

In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the highest activity of systemic lupus erythematosus. Our results show that native circulating IgG complexes from active systemic lupus erythematosus patients expose fucosyl residues and their glycan core is accessible to soluble lectins. Two putative mechanisms may contribute to the increased exposure of these glycans: (1) the canonical N-glycosylation site of the IgG-CH2 domain; (2) an IgG binding non-IgG molecule, like complement or C-reactive protein. In both cases the complexed IgG may be alternatively targeted to lectin receptors of effector cells, e.g. dendritic cells. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Pulmonary manifestations in systemic lupus erythematosus: pleural involvement, acute pneumonitis, chronic interstitial lung disease and diffuse alveolar hemorrhage.

PubMed

Aguilera-Pickens, Georgina; Abud-Mendoza, Carlos

2018-05-14

Systemic lupus erythematosus is the diffuse autoimmune connective tissue disease that most frequently involves pulmonary involvement, affecting 20% of 90% of the patients. The percentage varies depending on the defining criteria (symptoms, pulmonary tests or histopathological studies). At least once during the disease course, 50% of those affected have pleural and/or pulmonary manifestations, which are associated with higher morbidity and mortality. Pulmonary involvement has no correlation with lupus activity biomarkers, and it is necessary to rule out infectious processes in the initial approach. Bacterial infection is most frequently the cause of lung involvement in lupus and is one of the most important causes of death. Pulmonary involvement is considered to be primary when it is associated with disease activity, and secondary when other causes participate. Drugs have been reported to be associated with pulmonary damage, including interstitial disease. The incidence of malignant lung diseases is increased in systemic lupus erythematosus. Treatment depends on the type and severity of pulmonary involvement. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

Mast cells in systemic and cutaneous lupus erythematosus.

PubMed

Kaczmarczyk-Sekuła, Karolina; Dyduch, Grzegorz; Kostański, Marcin; Wielowieyska-Szybińska, Dorota; Szpor, Joanna; Białas, Magdalena; Okoń, Krzysztof

2015-12-01

Mast cells (MCs) are known to be regulators of inflammation and immunity, due to the released mediators and expressed cell surface molecules. Lupus erythematosus (LE) is a group of diseases which can be systemic or limited to the skin. Due to the fact that cytokines and chemokines produced by inflammatory cells contribute to the pathogenesis of LE, we quantified the number of mast cells present in the skin. The aim of the study was to compare the chymase-positive and tryptase-positive mast cell counts within skin biopsies from patients with systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). The material consisted of 45 skin biopsies: 6 with SLE, 34 with DLE and 5 with SCLE. Chymase- and tryptase-positive cells were stained by immunohistochemistry and counted. The mean count of chymase-positive mast cells was 85.14 hpf for the whole group, 35.83 for SLE, 88.48 for DLE and 121.6 for SCLE. The mean count of tryptase-positive cells was 120.05 hpf for the entire group, 59.17 for SLE, 126.42 for DLE and 149.8 for SCLE. The differences between groups were significant for chymase- and tryptase-positive cells.

Lupus mastitis: a mimicker of breast carcinoma

PubMed Central

Warne, Richard Roger; Taylor, Donna; Segal, Amanda; Irish, Ashley

2011-01-01

The authors present a case of lupus mastitis which was initially diagnosed following an incisional biopsy of a breast lump, with similar pathology found 2 years later after an ultrasound guided biopsy of the same lump. The woman had been diagnosed 7 years before with systemic lupus erythematosus. The radiological and pathological features are presented in this report with discussion of similar cases in the literature. PMID:22669997

PKK deficiency in B cells prevents lupus development in Sle lupus mice

PubMed Central

Oleksyn, D.; Zhao, J.; Vosoughi, A.; Zhao, JC.; Misra, R; Pentland, AP; Ryan, D.; Anolik, J.; Ritchlin, C.; Looney, J.; Anandarajah, AP.; Schwartz, G.; Calvi, LM; Georger, M; Mohan, C.; Sanz, I.; Chen, L

2018-01-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can result in damage to multiple organs. It is well documented that B cells play a critical role in the development of the disease. We previously showed that protein kinase C associated kinase (PKK) is required for B1 cell development as well as for the survival of recirculating mature B cells and B- lymphoma cells. Here, we investigated the role of PKK in lupus development in a lupus mouse model. We demonstrate that the conditional deletion of PKK in B cells prevents lupus development in Sle1Sle3 mice. The loss of PKK in Sle mice resulted in the amelioration of multiple classical lupus-associated phenotypes and histologic features of lupus nephritis, including marked reduction in the levels of serum autoantibodies, proteinuria, spleen size, peritoneal B-1 cell population and the number of activated CD4 T cells. In addition, the abundance of autoreactive plasma cells normally seen in Sle lupus mice was also significantly decreased in the PKK-deficient Sle mice. Sle B cells deficient in PKK display defective proliferation responses to BCR and LPS stimulation. Consistently, B cell receptor-mediated NF-κB activation, which is required for the survival of activated B cells, was impaired in the PKK-deficient B cells. Taken together, our work uncovers a critical role of PKK in lupus development and suggests that targeting the PKK-mediated pathway may represent a promising therapeutic strategy for lupus treatment. PMID:28274793

Development and validation of a disease-specific health-related quality of life measure, the LupusQol, for adults with systemic lupus erythematosus.

PubMed

McElhone, Kathleen; Abbott, Janice; Shelmerdine, Joanna; Bruce, Ian N; Ahmad, Yasmeen; Gordon, Caroline; Peers, Kate; Isenberg, David; Ferenkeh-Koroma, Ada; Griffiths, Bridget; Akil, Mohamed; Maddison, Peter; Teh, Lee-Suan

2007-08-15

To develop and validate a disease-specific health-related quality of life (HRQOL) instrument for adults with systemic lupus erythematosus (SLE). The work consisted of 6 stages. Stage 1 included item generation for questionnaire content from semistructured interviews with SLE patients. In stage 2 item selection for the draft questionnaire was performed by thematic analysis of the patient interview transcripts and expert panel agreement. In stage 3 the content validity of the draft questionnaire was assessed by patients completing the questionnaire and providing critical feedback. In stages 4 and 5 construct validity and internal reliability of the 3 versions of the LupusQoL were evaluated using principal component analysis with varimax rotation and Cronbach's alpha coefficients, respectively. In stage 6 discriminatory validity, concurrent validity, and test-retest reliability were evaluated. Stages 1, 2, and 3 resulted in a preliminary instrument containing 63 items. In stage 4, 8 domains were identified. This factor structure, accounting for 82% of the variance, was confirmed in stage 5. The domains and Cronbach's alpha coefficients were physical health (0.94), emotional health (0.94), body image (0.89), pain (0.92), planning (0.93), fatigue (0.88), intimate relationships (0.96), and burden to others (0.94). Discriminant validity was demonstrated for different levels of disease activity (British Isles Lupus Assessment Group Index) and damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). High correlations (r = 0.71-0.79) between comparable domains of the Short Form 36 and the LupusQoL assured acceptable concurrent validity. Good test-retest reliability (r = 0.72-0.93) was demonstrated. The LupusQoL is a validated SLE-specific HRQOL instrument with 34 items across 8 domains defined by patients as being important.

Evaluation of quality indicators and disease damage in childhood-onset systemic lupus erythematosus patients.

PubMed

Harris, Julia G; Maletta, Kristyn I; Kuhn, Evelyn M; Olson, Judyann C

2017-02-01

The aim of this study was to describe compliance with select quality indicators and assess organ-specific dysfunction in a childhood-onset systemic lupus erythematosus population by using a validated damage index and to evaluate associations between compliance with quality indicators and disease damage. A retrospective chart review was performed on patients diagnosed with systemic lupus erythematosus prior to age 18 followed at a single center in the USA from 1999 to 2012 (n = 75). Data regarding quality indicators and outcome variables, including the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, were collected. The median disease duration was 3.8 years. The proportion of patients or patient-years in which care complied with the proposed quality measures was 94.4% for hydroxychloroquine use, 84.3% for vitamin D recommendation,75.8% for influenza vaccination (patient-years), 67.2% for meningococcal vaccination, 49.0% for ophthalmologic examination (patient-years), 31.7% for pneumococcal vaccination, and 28.6% for bone mineral density evaluation. Disease damage was present in 41.3% of patients at last follow-up, with an average damage index score of 0.81. Disease damage at last follow-up was associated with minority race/ethnicity (p = 0.008), bone mineral density evaluation (p = 0.035), and vitamin D recommendation (p = 0.018). Adherence to quality indicators in a childhood-onset systemic lupus erythematosus population is varied, and disease damage is prevalent. This study highlights the importance of quality improvement initiatives aimed at optimizing care delivery to reduce disease damage in pediatric lupus patients.

Factors associated with health-related quality of life in Peruvian patients with systemic lupus erythematosus.

PubMed

Elera-Fitzcarrald, Claudia; Alva, Magaly; Gamboa-Cardenas, Rocío; Mora-Trujillo, Claudia S; Zevallos, Francisco; García-Poma, Augusto; Medina, Mariela; Rodriguez-Bellido, Zoila; Perich-Campos, Risto A; Pastor-Asurza, César A; Segami, María I; Ugarte-Gil, Manuel F

2018-05-01

Objective In this paper, we aim to define factors associated with health-related quality of life (HRQoL) in Mestizo patients with systemic lupus erythematosus (SLE). Methods We evaluated patients with SLE from Peru's two largest hospitals between October 2012 and July 2015 to ascertain HRQoL. Using a standard protocol, we incorporated demographic characteristics, clinical manifestations and treatment in our analysis. HRQoL was measured with the LupusQoL, disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and damage was appraised with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index (SDI). The associations between the LupusQoL and these variables were examined using linear regression models. Model selection was based on backward elimination. Results A total of 277 patients fit the inclusion criterion. Of these, 254 (91.7%) were female, the median (interquartile range, IQR) age at diagnosis was 41.5 (33.8-51.8) years, disease duration was 6.5 (2.7-11.3) years. The HRQoL domains most affected were the following: burden to others, fatigue, and intimate relationships. Through multivariate analysis, we determined that older age at diagnosis, higher disease activity, damage, and immunosuppressive drug use were negatively associated with HRQoL. Further, we found that higher socioeconomic status, disease duration, and antimalarial use were positively associated with HRQoL. Conclusion Age at diagnosis, disease activity, damage, and use of immunosuppressive drugs were negatively associated with HRQoL; high socioeconomic status, disease duration, and use of antimalarials were positively associated with HRQoL.

Specific Psychosocial and Behavioral Outcomes from the Systemic Lupus Erythematosus Self-Help Course.

ERIC Educational Resources Information Center

Braden, Carrie Jo; And Others

1993-01-01

Data from 104 participants in the Systemic Lupus Erythematosus Self-Help Course showed that patients had significant increases in enabling skills and use of relaxation/exercise and decreases in depression. Amount of time spent in class was correlated with significant changes over time. (SK)

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

PubMed Central

Kao, Amy H.; Manzi, Susan; Ahearn, Joseph M.

2013-01-01

The search for lupus biomarkers to diagnose, monitor, stratify, and predict individual response to therapy is currently more intense than ever before. This effort is essential for several reasons. First, epidemic overdiagnosis and underdiagnosis of lupus, even by certified rheumatologists, leads to errors in therapy with concomitant side effects which may be more serious than the disease itself. Second, identification of lupus flares remains as much an art as it is a science. Third, the capacity to stratify patients so as to predict those who will develop specific patterns of organ involvement is not currently possible but would potentially lead to preventive therapeutic strategies. Fourth, only one new drug for the treatment of lupus has been approved by the US Food and Drug Administration in over 50 years. A major obstacle in this pipeline is the dearth of biomarkers available to prove a patient has responded to an experimental therapeutic intervention. This review will summarize the challenges faced in the discovery and validation of lupus biomarkers, the most promising lupus biomarkers identified to date, and the promise of future directions. PMID:23904865

Drug-induced lupus erythematosus

MedlinePlus

... Tsokos GC, ed. Systemic Lupus Erythematosus . Philadelphia, PA: Elsevier; 2016:chap 54. Habif TP. Connective tissue diseases. ... TP, ed. Clinical Dermatology . 6th ed. Philadelphia, PA: Elsevier; 2016:chap 17. Kumar V, Abbas AK, Aster ...

Joint Aspiration (Arthrocentesis)

MedlinePlus

... arthritis, or JRA), systemic lupus erythematosus (SLE), and Lyme disease. Joint aspiration is diagnostic but it also can ... topic for: Parents Kids Teens Evaluate Your Child's Lyme Disease Risk Living With Lupus Bones, Muscles, and Joints ...

Periorbital edema in systemic lupus erythematosus.

PubMed

Smith, C A; Pinals, R S

1982-09-01

We have seen two patients with systemic lupus erythematosus (LE) and chronic periorbital edema. Periorbital edema occurs frequently in dermatomyositis, but it has rarely been noted in systemic LE. The edema may be associated with facial rash, but it is unrelated to the occurrence of nephrotic syndrome, cardiac and hepatic dysfunction, or edema elsewhere. This complication of systemic LE may be relatively refractory to corticosteroid therapy.

Diagnosis and early detection of CNS-SLE in MRL/lpr mice using peptide microarrays.

PubMed

Williams, Stephanie; Stafford, Phillip; Hoffman, Steven A

2014-06-07

An accurate method that can diagnose and predict lupus and its neuropsychiatric manifestations is essential since currently there are no reliable methods. Autoantibodies to a varied panel of antigens in the body are characteristic of lupus. In this study we investigated whether serum autoantibody binding patterns on random-sequence peptide microarrays (immunosignaturing) can be used for diagnosing and predicting the onset of lupus and its central nervous system (CNS) manifestations. We also tested the techniques for identifying potentially pathogenic autoantibodies in CNS-Lupus. We used the well-characterized MRL/lpr lupus animal model in two studies as a first step to develop and evaluate future studies in humans. In study one we identified possible diagnostic peptides for both lupus and altered behavior in the forced swim test. When comparing the results of study one to that of study two (carried out in a similar manner), we further identified potential peptides that may be diagnostic and predictive of both lupus and altered behavior in the forced swim test. We also characterized five potentially pathogenic brain-reactive autoantibodies, as well as suggested possible brain targets. These results indicate that immunosignaturing could predict and diagnose lupus and its CNS manifestations. It can also be used to characterize pathogenic autoantibodies, which may help to better understand the underlying mechanisms of CNS-Lupus.

Dietary micronutrient intake and atherosclerosis in systemic lupus erythematosus.

PubMed

Lourdudoss, C; Elkan, A-C; Hafström, I; Jogestrand, T; Gustafsson, T; van Vollenhoven, R; Frostegård, J

2016-12-01

The aim of this study was to investigate the role of dietary micronutrient intake in systemic lupus erythematosus (SLE). This study included 111 SLE patients and 118 age and gender-matched controls. Data on diet (food frequency questionnaires) were linked with data on Systemic Lupus Activity Measure, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and carotid atherosclerotic/echolucent plaque (B-mode ultrasound). Dietary micronutrient intake were compared between SLE patients and controls and in relation to lupus activity and atherosclerosis in SLE. Associations between micronutrient intake and plaque were analyzed through logistic regression, adjusted for potential confounders. Micronutrient intake did not differ between patients and controls, and between lower and higher lupus activity, apart from the fact that phosphorus was associated with SLEDAI > 6. In SLE patients, some micronutrients were associated with atherosclerotic plaque, left side. Lower intake of riboflavin and phosphorus was associated with atherosclerotic plaque, left side (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.12-8.40 and OR 4.36, 95% CI 1.53-12.39, respectively). Higher intake of selenium and thiamin was inversely associated with atherosclerotic plaque, left side (OR 0.28, 95% CI 0.09-0.89 and OR 0.26, 95% CI 0.08-0.80, respectively). In addition, higher intake of thiamin was inversely associated with echolucent plaque, left side (OR 0.22, 95% CI 0.06-0.84). Lower intake of folate was inversely associated with bilateral echolucent plaque (OR 0.36, 95% CI 0.13-0.99). SLE patients did not have different dietary micronutrient intake compared to controls. Phosphorus was associated with lupus activity. Riboflavin, phosphorus, selenium and thiamin were inversely associated with atherosclerotic plaque, left side in SLE patients, but not in controls. Dietary micronutrients may play a role in atherosclerosis in SLE. © The Author(s) 2016.

Association of Discoid Lupus with Clinical Manifestations and Damage Accrual in PROFILE: A Multiethnic Lupus Cohort

PubMed Central

Santiago-Casas, Yesenia; Vilá, Luis M.; McGwin, Gerald; Cantor, Ryan S.; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D.; Kimberly, Robert P.; Alarcón, Graciela S.; Brown, Elizabeth E.

2013-01-01

Objective To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort. Methods SLE patients (per ACR criteria), age ≥ 16 years, disease duration ≤ 10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal cohort were studied. Socioeconomic-demographic features, clinical manifestations and disease damage [as per the Systemic Lupus International Collaborating Clinics Damage Index (SDI)] were determined. The association of DLE with clinical manifestations and disease damage was examined using multivariable logistic regression. Results A total of 2,228 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.3 (12.8) years and the mean (SD) disease duration was 7.9 (6.0) years; 91.8% were women. Discoid lupus was observed in 393 (17.6%) of patients with SLE. In the multivariable analysis, patients with discoid lupus were more likely to be smokers and of African-American ethnicity, and to have malar rash, photosensitivity, oral ulcers, leukopenia and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity, and to have arthritis, end-stage renal disease (ESRD), and antinuclear, anti-dsDNA and anti-phospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers. Conclusion In this cohort of SLE patients, discoid lupus was associated with several clinical features including serious manifestations such as vasculitis and chronic seizures. PMID:22190480

Multiplicity At Early Stages Of Star Formation, Small Clusters. Observations Overview

NASA Astrophysics Data System (ADS)

Saito, Masao

2017-07-01

The SOLA (Soul of Lupus with ALMA) project is conducting comprehensive studies of the Lupus Molecular Clouds and their star formation processes covering 10-10^4 AU scale. Our goal is to exploit ALMA and other facilities over a wide wavelength range to establish a prototypical low-mass star forming scenario based on the Lupus region. In the presentation, we will focus on angular momentum in dense cores in a filament, molecular outflows from young stars, and Class 0/I binary survey in Lupus as well as overview of our projects. Our binary survey was conducted in ALMA cycle 2 and achieved at 0.2-0.3 arcsec resolution discovering new binary systems in Lupus. At the same time, we obtained EX Lup, EXor type burst source, data in ALMA Cycle 3.

Multiplicity at Early Stages of Star Formation, Small Clusters. Observations Overview

NASA Astrophysics Data System (ADS)

Saito, Masao

2017-06-01

The SOLA (Soul of Lupus with ALMA) project is conducting comprehensive studies of the Lupus Molecular Clouds and their star formation processes covering 10-10^4 AU scale. Our goal is to exploit ALMA and other facilities over a wide wavelength range to establish a prototypical low-mass star forming scenario based on the Lupus region. In the presentation, we will focus on angular momentum in dense cores in a filament, molecular outflows from young stars, and Class 0/I binary survey in Lupus as well as overview of our projects. Our binary survey was conducted in ALMA cycle 2 and achieved at 0.2-0.3 arcsec resolution discovering new binary systems in Lupus. At the same time, we obtained EX Lup, EXor type burst source, data in ALMA Cycle 3.

Epstein-Barr virus-associated hemophagocytic syndrome in a patient with lupus nephritis.

PubMed

Isome, Masato; Suzuki, Junzo; Takahashi, Ai; Murai, Hiromichi; Nozawa, Ruriko; Suzuki, Shigeo; Kawasaki, Yukihiko; Suzuki, Hitoshi

2005-02-01

Hemophagocytic syndrome (HPS) is an unusual but severe illness associated with a variety of infections, as well as genetic, malignant tumors, and autoimmune diseases. We report an 11-year-old girl with systemic lupus erythematosus and nephritis who developed HPS associated with Epstein-Barr virus reactivation. In our patient, the onset of reactive HPS might be related to immunosuppressive treatment during the course of lupus nephritis.

The study of Cutaneous Lupus Erythematosus Disease Area and Severity Index in Indian patients with systemic lupus erythematosus.

PubMed

Salphale, P; Danda, D; Chandrashekar, L; Peter, D; Jayaseeli, N; George, R

2011-12-01

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a newly described tool used to assess the activity of and damage caused by cutaneous lupus erythematosus (CLE). There is a paucity of data on CLASI from the Indian subcontinent. We sought to determine the applicability of CLASI in specific lesions of CLE in patients with systemic lupus erythematosus (SLE) attending a tertiary care hospital in India. In this prospective, cross-sectional study, 93 patients of SLE with cutaneous lesions were recruited. CLASI activity and damage scores of lupus erythematosus (LE)-specific skin lesions were done in 75 patients with SLE. The mean CLASI activity score was 15.4 ± 9.4 (range 0-39) and the mean damage score was 6.87 ± 7.75 (range 0-30). Higher mean CLASI activity scores were seen in patients with a combination of acute, subacute and chronic CLE and in those with widespread lesions. Patients with longstanding disease and long duration of skin lesions had higher damage scores. This study shows that CLASI is an effective tool to assess cutaneous activity of LE-specific lesions, and the damage caused by them, in Indian patients.

Systemic Lupus Erythematosus: Molecular Mimicry between Anti-dsDNA CDR3 Idiotype, Microbial and Self Peptides-As Antigens for Th Cells.

PubMed

Aas-Hanssen, Kristin; Thompson, Keith M; Bogen, Bjarne; Munthe, Ludvig A

2015-01-01

Systemic lupus erythematosus (SLE) is marked by a T helper (Th) cell-dependent B cell hyperresponsiveness, with frequent germinal center reactions, and gammaglobulinemia. A feature of SLE is the finding of IgG autoantibodies specific for dsDNA. The specificity of the Th cells that drive the expansion of anti-dsDNA B cells is unresolved. However, anti-microbial, anti-histone, and anti-idiotype Th cell responses have been hypothesized to play a role. It has been entirely unclear if these seemingly disparate Th cell responses and hypotheses could be related or unified. Here, we describe that H chain CDR3 idiotypes from IgG(+) B cells of lupus mice have sequence similarities with both microbial and self peptides. Matched sequences were more frequent within the mutated CDR3 repertoire and when sequences were derived from lupus mice with expanded anti-dsDNA B cells. Analyses of histone sequences showed that particular histone peptides were similar to VDJ junctions. Moreover, lupus mice had Th cell responses toward histone peptides similar to anti-dsDNA CDR3 sequences. The results suggest that Th cells in lupus may have multiple cross-reactive specificities linked to the IgVH CDR3 Id-peptide sequences as well as similar DNA-associated protein motifs.

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus.

PubMed

Sanchez, Elena; Nadig, Ajay; Richardson, Bruce C; Freedman, Barry I; Kaufman, Kenneth M; Kelly, Jennifer A; Niewold, Timothy B; Kamen, Diane L; Gilkeson, Gary S; Ziegler, Julie T; Langefeld, Carl D; Alarcón, Graciela S; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Brown, Elizabeth E; Kimberly, Robert P; Reveille, John D; Vilá, Luis M; Merrill, Joan T; Anaya, Juan-Manuel; James, Judith A; Pons-Estel, Bernardo A; Martin, Javier; Park, So-Yeon; Bang, So-Young; Bae, Sang-Cheol; Moser, Kathy L; Vyse, Timothy J; Criswell, Lindsey A; Gaffney, Patrick M; Tsao, Betty P; Jacob, Chaim O; Harley, John B; Alarcón-Riquelme, Marta E; Sawalha, Amr H

2011-10-01

Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. 4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10(-6), OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of <0.05 and pass the significance threshold using Bonferroni correction for multiple testing. Signifi cant associations were found between clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future.

Suppressor cell hyperactivity relative to allogeneic lymphocyte proliferation as a manifestation of defective T-T-cell interactions in systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stenina, M.A.; Potapova, A.A.; Biryukov, A.V.

1987-01-01

The authors study the state of immunoregulatory process in patients with systemic lupus erythematosus at the T-T-cell interaction level and seek to test the possibility of the pharmacological modulation of this process. The proliferative activity of mononuclear lymphocytes, extracted from the blood of ten lupus patients, was assessed by measuring the incorporation of tritiated thymidine into cultures stimulated by phytohemagglutinin, concanavalin, and theophylline. The comparative effects of each of these agents on the immunoregulatory and proliferative activity of the lymphocytes are reported.

Streptococcus pneumoniae necrotizing fasciitis in systemic lupus erythematosus.

PubMed

Sánchez, A; Robaina, R; Pérez, G; Cairoli, E

2016-04-01

Necrotizing fasciitis is a rapidly progressive destructive soft tissue infection with high mortality. Streptococcus pneumoniae as etiologic agent of necrotizing fasciitis is extremely unusual. The increased susceptibility to Streptococcus pneumoniae infection in patients with systemic lupus erythematosus is probably a multifactorial phenomenon. We report a case of a patient, a 36-year-old Caucasian female with 8-year history of systemic lupus erythematosus who presented a fatal Streptococcus pneumoniae necrotizing fasciitis. The role of computed tomography and the high performance of blood cultures for isolation of the causative microorganism are emphasized. Once diagnosis is suspected, empiric antibiotic treatment must be prescribed and prompt surgical exploration is mandatory. © The Author(s) 2015.

Reprint of: B cell elimination in systemic lupus erythematosus. Clin. Immunol. 146(2) 90-103.

PubMed

Furtado, João; Isenberg, David A

2013-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Development of primary central nervous system lymphoma in a systemic lupus erythematosus patient after treatment with mycophenolate mofetil and review of the literature.

PubMed

Balci, M A; Pamuk, G E; Unlu, E; Usta, U; Pamuk, O N

2017-10-01

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma and four cases of PCNSL have previously been described in association with mycophenolate mofetil. We report the fifth case of PCNSL in a patient with lupus nephropathy while on mycophenolate mofetil treatment.

Hydroxychloroquine inhibits CD154 expression in CD4+ T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling.

PubMed

Wu, Shu-Fen; Chang, Chia-Bin; Hsu, Jui-Mei; Lu, Ming-Chi; Lai, Ning-Sheng; Li, Chin; Tung, Chien-Hsueh

2017-08-09

Overexpression of membranous CD154 in T lymphocytes has been found previously in systemic lupus erythematosus (SLE). Because hydroxychloroquine (HCQ) has been used frequently in the treatment of lupus, we sought to identify the effects of HCQ on CD154 and a possibly regulatory mechanism. CD4 + T cells were isolated from the blood of lupus patients. After stimulation with ionomycin or IL-15 and various concentrations of HCQ, expression of membranous CD154 and NFAT and STAT5 signaling were assessed. HCQ treatment had significant dose-dependent suppressive effects on membranous CD154 expression in ionomycin-activated T cells from lupus patients. Furthermore, HCQ inhibited intracellular sustained calcium storage release, and attenuated the nuclear translocation of NFATc2 and the expression of NFATc1. However, CD154 expressed through IL-15-mediated STAT5 signaling was not inhibited by HCQ treatment. HCQ inhibited NFAT signaling in activated T cells and blocked the expression of membranous CD154, but not STAT5 signaling. These findings provide a mechanistic insight into SLE in HCQ treatment.

Treating lupus in the kidney: where are we now, and where are we going?

PubMed

Canetta, Pietro A A; Bomback, Andrew S; Radhakrishnan, Jai

2011-10-01

Kidney involvement is a frequent and dreaded consequence of systemic lupus erythematosus. While historically this condition was devastatingly morbid, over the past thirty years an improved understanding of the disease's pathobiology has accompanied increasingly effective treatment regimens that have dramatically improved the prognosis for affected patients. Induction and maintenance of remission can now be obtained in the majority of patients, although at least 20-30% may be refractory to treatment. What's more, the standard drugs in use for lupus nephritis remain fairly broad immunosuppressants, and carry notable risks and side effects. Recent years have witnessed an explosion in the number of novel immunomodulatory drugs being developed, with increasingly specific targets of action in the immune system. These molecules hold promise for a range of autoimmune disorders, including lupus nephritis, and several are already being actively investigated for that purpose. Here we review the current state of the art in the treatment of lupus nephritis, highlight the limits of standard treatments, and discuss the most promising of the novel therapies coming down the pipeline.

Clozapine-induced systemic lupus erythematosus.

PubMed

Rami, Abu Fanne; Barkan, Daniel; Mevorach, Dror; Leitersdorf, Eran; Caraco, Yoseph

2006-05-01

To report a case of classic clozapine-induced systemic lupus erythematosus that also developed on rechallenge. A 32-year-old white woman diagnosed with schizophrenia presented in 1996 with clinical characteristics and laboratory markers consistent with drug-induced lupus (DIL). Clozapine, started 1 year prior, was withdrawn, with complete biological and clinical remission within 3 months. In 2004, 1 week after rechallenge with clozapine for uncontrolled schizophrenia, the patient developed clinical and biological signs and symptoms consistent with the diagnosis of DIL. Again, discontinuation of clozapine was followed by full remission within 2-3 months. DIL was first described more than 50 years ago, with multiple drugs implicated in the causation. Clozapine-induced lupus was reported recently, but does not meet the usual criteria for a diagnosis of DIL. We report a classic case of clozapine-induced lupus that, according to the Naranjo probability scale, demonstrates a highly probable relationship between DIL and clozapine. DIL demands a high index of suspicion for diagnosis. Although clozapine has an extensive safety profile, DIL must be considered as one of its serious adverse effects.

Involvement of scalp and nails in lupus erythematosus.

PubMed

Trüeb, R M

2010-08-01

Lupus erythematosus (LE) is a systemic autoimmune disorder associated with polyclonal B-cell activation resulting in diverse patterns of autoantibody production and a heterogeneous clinical expression constituting a spectrum extending from limited cutaneous disease to life-threatening systemic manifestations. For daily clinical practice, the characteristics of cutaneous lupus erythematosus (CLE) have been well defined in terms of morphology, and clinical and laboratory criteria are available for the classification as systemic lupus erythematosus (SLE). The many different types of skin lesions encountered in patients with LE have been classified into those that are histologically specific for LE and those that are not. While LE non-specific skin lesions on their own do not enable a diagnosis of LE, they can be important reflections of underlying SLE disease activity. This also applies to the involvement of the scalp and nails. Finally, it must be kept in mind that LE patients may also develop drug-related, or other unrelated common disorders of the hair and nails that do not reflect LE disease activity.

Systemic lupus erythematosus and renal tubular acidosis associated with hyperthyroidism. Case Report.

PubMed

Deng, Datong; Sun, Li; Xia, Tongjia; Xu, Min; Wang, Youmin; Zhang, Qiu

2016-07-01

A case of a 42-year-old female with hyperthyroidism was subsequently diagnosed to have systemic lupus erythematosus with distal RTA. The clinical examination on admission showed swelling of the knee joints and the urinalysis showed pH 6.5, pro 3+. Her blood routine results were as follows: white blood cells 1.85×109/L, platelets 100×109/L, erythrocyte 3.06×1012/L. The serum potassium was 3.11 mmol/L, 24 hour urinary electrolyte: K 68.87 mmol/24 H, antinuclear antibodies (ANA) 1:1 000, speckled pattern. The anti-double stranded DNA antibody (anti-dsDNA), anti SS-A(52) antibody and anti SS-A(60) antibody were positive. The light microscopy and immunofluorescence showed diffuse proliferative lupus nephritis. These data were compatible with the diagnosis of systemic lupus erythematosus. The diagnosis of hyperthyroidism and distal RTA is clear. This report showed that other autoimmune disease in the diagnosis of hyperthyroidism should not be ignored.

[Systemic lupus erythematosus in the pregnant patient. Implications for anesthesia].

PubMed

Pastor Tomás, E; Guillén Antón, J; Vaquerizo Gareta, A; Lirola Grajales, P; Martínez García, R; Cuartero Lobera, J

2001-03-01

A 28-year-old woman with systemic lupus erythematosus and a history of aseptic meningitis, digestive bleeding due to thrombopenia and deep venous thrombosis underwent elective cesarean for transverse presentation at 35 weeks. Preoperative blood work-up showed an antinuclear antibody titre that was slightly positive and steroid treatment was started. Surgery operation was performed with general anesthesia. The outcome was satisfactory even though serious complications can develop during the management of anesthesia in such patients. Systemic lupus erythematosus is a chronic, multisystemic disease that mainly affects women of childbearing age. Antibodies and immunocomplexes play a fundamental role. Given the multiorgan involvement in this disease, preoperative study of the lupus patient should assess all such involvement, including maternal-fetal risk, as well as consider the drug and anesthetic management to be applied. Among the clinical signs that can affect management of anesthesia are the following: aseptic meningitis, high blood pressure, pericarditis, pneumonitis and recurrent venous thrombosis. Anemia, thrombopenia and significantly altered coagulation events are common.

Alterations in nuclear structure promote lupus autoimmunity in a mouse model

PubMed Central

Singh, Namrata; Johnstone, Duncan B.; Martin, Kayla A.; Tempera, Italo; Kaplan, Mariana J.

2016-01-01

ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the development of autoantibodies that recognize components of the cell nucleus. The vast majority of lupus research has focused on either the contributions of immune cell dysfunction or the genetics of the disease. Because granulocytes isolated from human SLE patients had alterations in neutrophil nuclear morphology that resembled the Pelger–Huet anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor (LBR), consistent with their Pelger–Huet-like nuclear morphology, we used a novel mouse model system to test the hypothesis that a disruption in the structure of the nucleus itself also contributes to the development of lupus autoimmunity. The lupus-prone mouse strain New Zealand White (NZW) was crossed with c57Bl/6 mice harboring a heterozygous autosomal dominant mutation in Lbr (B6.Lbric/+), and the (NZW×B6.Lbric)F1 offspring were evaluated for induction of lupus autoimmunity. Only female (NZW×B6.Lbric)F1 mice developed lupus autoimmunity, which included splenomegaly, kidney damage and autoantibodies. Kidney damage was accompanied by immune complex deposition, and perivascular and tubule infiltration of mononuclear cells. The titers of anti-chromatin antibodies exceeded those of aged female MRL-Faslpr mice, and were predominantly of the IgG2 subclasses. The anti-nuclear antibody staining profile of female (NZW×B6.Lbric)F1 sera was complex, and consisted of an anti-nuclear membrane reactivity that colocalized with the A-type lamina, in combination with a homogeneous pattern that was related to the recognition of histones with covalent modifications that are associated with gene activation. An anti-neutrophil IgM recognizing calreticulin, but not myeloperoxidase (MPO) or proteinase 3 (PR3), was also identified. Thus, alterations in nuclear structure contribute to lupus autoimmunity when expressed in the context of a lupus-prone genetic background, suggesting a mechanism for the development of lupus autoimmunity in genetically predisposed individuals that is induced by the disruption of nuclear architecture. PMID:27483354

Toxic shock syndrome in a patient with systemic lupus erythematosus.

PubMed Central

Chan, R. M.; Graham, H. R.; Birmingham, C. L.

1983-01-01

A case is presented of toxic shock syndrome in a patient with systemic lupus erythematosus. Toxic shock syndrome is rarely reported in patients who are immunosuppressed, perhaps because such patients are often treated vigorously with antibiotics at the earliest sign of infection. The association in this case may have been coincidental. PMID:6640456

Incidence of Systemic Lupus Erythematosus in a Population Based Cohort using Revised 1997 American College of Rheumatology and the 2012 Systemic Lupus International Collaborating Clinic Classification Criteria

PubMed Central

Ungprasert, Patompong; Sagar, Vinay; Crowson, Cynthia S.; Amin, Shreyasee; Makol, Ashima; Ernste, Floranne C.; Osborn, Thomas G.; Moder, Kevin G.; Niewold, Timothy B.; Maradit-Kremers, Hilal; Ramsey-Goldman, Rosalind; Chowdhary, Vaidehi R.

2016-01-01

In 2012, the Systemic Lupus International Collaborating Clinic (SLICC) group published a new set of classification criteria for systemic lupus erythematosus (SLE). Studies applying these criteria to real life scenarios have found either equal or greater sensitivity and equal or lower specificity to the 1997 ACR classification criteria (ACR 97). Nonetheless, there are no studies that have used the SLICC 12 criteria to investigate the incidence of lupus. We utilized the resource of the Rochetser Epidemiology Project to identify incident cases of SLE in Olmsted County, Minnesota from 1993-2005 who fulfilled the ACR 97 or SLICC 12 criteria. A total of 58 patients met criteria by SLICC 12 and 44 patients met criteria by ACR 97. The adjusted incidence of 4.9 per 100,000 person-years by SLICC 12 was higher than that by ACR 97 (3.7 per 100,000 person-years, p=0.04). The median duration from the appearance of first criteria to fulfillment of the criteria was shorter for the SLICC 12 than for ACR 97 (3.9 months vs 8.1 months). The higher incidence by SLICC 12 criteria came primarily from the ability to classify patients with renal-limited disease, the expansion of the immunologic criteria and the expansion of neurologic criteria. PMID:27365370

Incidence of systemic lupus erythematosus in a population-based cohort using revised 1997 American College of Rheumatology and the 2012 Systemic Lupus International Collaborating Clinics classification criteria.

PubMed

Ungprasert, P; Sagar, V; Crowson, C S; Amin, S; Makol, A; Ernste, F C; Osborn, T G; Moder, K G; Niewold, T B; Maradit-Kremers, H; Ramsey-Goldman, R; Chowdhary, V R

2017-03-01

In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group published a new set of classification criteria for systemic lupus erythematosus (SLE). Studies applying these criteria to real-life scenarios have found either equal or greater sensitivity and equal or lower specificity to the 1997 ACR classification criteria (ACR 97). Nonetheless, there are no studies that have used the SLICC 12 criteria to investigate the incidence of lupus. We used the resource of the Rochester Epidemiology Project to identify incident SLE patients in Olmsted County, Minnesota, from 1993 to 2005, who fulfilled the ACR 97 or SLICC 12 criteria. A total of 58 patients met criteria by SLICC 12 and 44 patients met criteria by ACR 97. The adjusted incidence of 4.9 per 100,000 person-years by SLICC 12 was higher than that by ACR 97 (3.7 per 100,000 person-years, p = 0.04). The median duration from the appearance of first criterion to fulfillment of the criteria was shorter for the SLICC 12 than for ACR 97 (3.9 months vs 8.1 months). The higher incidence by SLICC 12 criteria came primarily from the ability to classify patients with renal-limited disease, the expansion of the immunologic criteria and the expansion of neurologic criteria.

Effect of total lymphoid irradiation on levels of serum autoantibodies in systemic lupus erythematosus and in rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanay, A.; Schiffman, G.; Strober, S.

1986-01-01

The effects of total lymphoid irradiation (TLI) on serum levels of autoantibodies, and of antibodies to diphtheria toxoid, tetanus toxoid, and pneumococcal polysaccharide in patients with lupus nephritis were compared with those previously observed in rheumatoid arthritis (RA) patients. Baseline levels of antibodies to diphtheria toxoid and tetanus toxoid decreased significantly after TLI in patients with lupus and RA, but antibody levels to pneumococcal polysaccharide remained unchanged. After TLI, the levels of antinuclear and anti-DNA antibodies were reduced significantly in lupus, but levels of rheumatoid factor, antinuclear, and antigranulocyte antibodies all tended to increase in RA.

Gastrointestinal system involvement in systemic lupus erythematosus.

PubMed

Li, Z; Xu, D; Wang, Z; Wang, Y; Zhang, S; Li, M; Zeng, X

2017-10-01

Systemic lupus erythematosus (SLE) is a multisystem disorder which can affect the gastrointestinal (GI) system. Although GI symptoms can manifest in 50% of patients with SLE, these have barely been reviewed due to difficulty in identifying different causes. This study aims to clarify clinical characteristics, diagnosis and treatment of the four major SLE-related GI system complications: protein-losing enteropathy (PLE), intestinal pseudo-obstruction (IPO), hepatic involvement and pancreatitis. It is a systematic review using MEDLINE and EMBASE databases and the major search terms were SLE, PLE, IPO, hepatitis and pancreatitis. A total of 125 articles were chosen for our study. SLE-related PLE was characterized by edema and hypoalbuminemia, with Technetium 99m labeled human albumin scintigraphy ( 99m Tc HAS) and alpha-1-antitrypsin fecal clearance test commonly used as diagnostic test. The most common site of protein leakage was the small intestine and the least common site was the stomach. More than half of SLE-related IPO patients had ureterohydronephrosis, and sometimes they manifested as interstitial cystitis and hepatobiliary dilatation. Lupus hepatitis and SLE accompanied by autoimmune hepatitis (SLE-AIH overlap) shared similar clinical manifestations but had different autoantibodies and histopathological features, and positive anti-ribosome P antibody highly indicated the diagnosis of lupus hepatitis. Lupus pancreatitis was usually accompanied by high SLE activity with a relatively high mortality rate. Early diagnosis and timely intervention were crucial, and administration of corticosteroids and immunosuppressants was effective for most of the patients.

Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

PubMed

Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A

2017-08-01

Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

The impact of tabalumab on the kidney in systemic lupus erythematosus: results from two phase 3 randomized, clinical trials.

PubMed

Rovin, B H; Dooley, M A; Radhakrishnan, J; Ginzler, E M; Forrester, T D; Anderson, P W

2016-12-01

Tabalumab is a monoclonal antibody that neutralizes membrane and soluble B-cell activating factor. Two 52-week, randomized, double-blind, placebo controlled phase 3 trials evaluated the safety and efficacy of tabalumab in systemic lupus erythematosus. Patients with moderate to severe active systemic lupus erythematosus (without severe active lupus nephritis) were randomly assigned 1:1:1 to receive tabalumab (120 mg subcutaneously every 2 or 4 weeks) or placebo for 52 weeks. Serum creatinine concentration, estimated glomerular filtration rate, urine protein/creatinine ratio, renal flares and renal adverse events were determined monthly. Data were analyzed for the intent-to-treat population and for intent-to-treat patients with baseline urine protein/creatinine ratio >20 mg/mmol (intent-to-treat plus urine protein/creatinine ratio). The trials enrolled 2262 patients. At baseline, demographics, systemic lupus erythematosus disease activity, serum creatinine concentration, estimated glomerular filtration rate and urine protein/creatinine ratio were similar among the treatment arms (with the exception of disease duration). In the intent-to-treat and intent-to-treat plus urine protein/creatinine ratio populations, there were no differences between the arms in the baseline-to-endpoint change in serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates. Tabalumab resulted in a significant B-cell reduction and decreased immunoglobulin G levels at both doses. Compared to placebo, tabalumab did not significantly affect the serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates over 1 year in intent-to-treat or intent-to-treat plus urine protein/creatinine ratio patients. There were no significant renal safety signals.ClinicalTrials.gov identifiers: NCT01205438 and NCT01196091 Lupus (2016) 25, 1597-1601. © The Author(s) 2016.

Cerebral tuberculosis in a patient with systemic lupus erythematosus following cyclophosphamide treatment: a case report.

PubMed

Cooray, S; Zhang, H; Breen, R; Carr-White, G; Howard, R; Cuadrado, M; D'Cruz, D; Sanna, G

2018-04-01

Central nervous system (CNS) tuberculosis (TB) is a rare but catastrophic event in patients with systemic lupus erythematosus (SLE). Here we report a case of cerebral TB in a patient with lupus myocarditis and nephritis, following cyclophosphamide immunosuppression. To our knowledge this is the first reported case of cerebral TB in SLE in a non-endemic country. A 31-year-old female with SLE and a history of regular travel to Kenya presented to our centre with clinical features of acute heart failure. She was diagnosed with severe lupus myocarditis, and a renal biopsy also confirmed lupus nephritis. Prior to admission, she had also had a cough, fever and weight loss and was under investigation for suspected TB infection. She was treated with ivabradine, beta-blockers and diuretics together with methylprednisolone and cyclophosphamide immunosuppression. Subsequent sputum cultures confirmed TB and she was commenced on triple therapy. Despite this, she developed confusion, dizziness, blurred vision and fluctuating consciousness. Magnetic resonance imaging (MRI) and lumbar puncture revealed CNS TB infection resulting in meningitis. This was later complicated by obstructive hydrocephalus due to TB abscesses. A ventriculoperitoneal (VP) shunt was inserted and TB medications were given intravenously (IV) with dexamethasone. Following a prolonged hospital admission, the patient eventually recovered and rituximab treatment was used to control her SLE. TB infection has been associated with SLE flares. It is likely in this case that TB exacerbated a lupus flare and subsequent immunosuppression resulted in mycobacterial dissemination to the CNS. Systemic and CNS features of TB and SLE are difficult to distinguish and their contemporaneous management represents a diagnostic and therapeutic challenge.

Systemic lupus erythematosus in a multiethnic U.S. cohort (LUMINA) XXVII: factors predictive of a decline to low levels of disease activity.

PubMed

Bertoli, A M; Alarcón, G S; McGwin, G; Fernández, M; Bastian, H M; Fessler, B J; Vilá, L M; Reveille, J D

2006-01-01

The objective of this study was to examine factors predictive of a decline to low levels of disease activity in a cohort of systemic lupus erythematosus (SLE) patients. Patients with SLE of Hispanic (from Texas or Puerto Rico), African-American or Caucasian ethnicity from a multiethnic cohort were included. A decline to low levels of disease activity was defined as a score < or =5 as per the Systemic Lupus Activity Measure-Revised (SLAM-R) at any annual study visit if preceded by a SLAM-R > or =8. Using Generalized Estimating Equation (GEE), socioeconomic-demographic, behavioral, function, psychological, laboratory and clinical data [disease manifestations, number of ACR criteria accrued at diagnosis and damage accrual as per the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI)] from the visit preceding that meeting the definition were examined as predictors of decline to low levels of disease activity. Two-hundred and eighty-seven patients (67 Hispanics from Texas, 32 Hispanics form Puerto Rico, 120 African-Americans and 68 Caucasians), accounting for 632 visits were analyzed. In the GEE multivariable analysis, higher degrees of social support (OR = 1.208, 95% CI 1.059-1.379; P = 0.005) were predictive of a decline to low levels of disease activity, while the number of ACR criteria accrued at diagnosis (OR = 0.765, 95% CI 0.631-0.927; P = 0.006) and damage (OR = 0.850, 95% CI 0.743-0.972, P = 0.018) were negatively associated. These data suggest that a decline to low levels of disease activity in lupus patients seems to be multifactorial; this study also underscores the importance of social support for lupus patients.

Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis.

PubMed

Mistry, Pragnesh; Kaplan, Mariana J

2017-12-01

Nephritis is one of the most severe complications of systemic lupus erythematosus (SLE). One key characteristic of lupus nephritis (LN) is the deposition of immune complexes containing nucleic acids and/or proteins binding to nucleic acids and autoantibodies recognizing these molecules. A variety of cell death processes are implicated in the generation and externalization of modified nuclear autoantigens and in the development of LN. Among these processes, apoptosis, primary and secondary necrosis, NETosis, necroptosis, pyroptosis, and autophagy have been proposed to play roles in tissue damage and immune dysregulation. Cell death occurs in healthy individuals during conditions of homeostasis yet autoimmunity does not develop, at least in part, because of rapid clearance of dying cells. In SLE, accelerated cell death combined with a clearance deficiency may lead to the accumulation and externalization of nuclear autoantigens and to autoantibody production. In addition, specific types of cell death may modify autoantigens and alter their immunogenicity. These modified molecules may then become novel targets of the immune system and promote autoimmune responses in predisposed hosts. In this review, we examine various cell death pathways and discuss how enhanced cell death, impaired clearance, and post-translational modifications of proteins could contribute to the development of lupus nephritis. Published by Elsevier Inc.

Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus.

PubMed

Liphaus, Bernadete L; Jesus, Adriana A; Silva, Clovis A; Coutinho, Antonio; Carneiro-Sampaio, Magda

2012-11-01

The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 ± 163.4 IU/ml (range 3.5-9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 ± 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels (r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus.

PubMed

Lu, P; Fleischmann, R; Curtis, C; Ignatenko, S; Clarke, S H; Desai, M; Wong, S L; Grebe, K M; Black, K; Zeng, J; Stolzenbach, J; Medema, J K

2018-02-01

Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax. Eligible participants were aged 18-65 years with a diagnosis of systemic lupus erythematosus for 6 months or more receiving stable therapy for systemic lupus erythematosus (which could have included corticosteroids and/or stable antimalarials). Results All patients (48/48) completed the single ascending dose, 25 continued into the multiple ascending dose, and 44/50 completed the multiple ascending dose; two of the withdrawals (venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event incidences were slightly higher in the venetoclax groups compared with the placebo groups, with no dose dependence. There were no serious adverse events with venetoclax. The most common adverse events were headache, nausea, and fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total lymphocytes and B cells by approximately 50% and 80%, respectively. Naive, switched memory, and memory B-cell subsets enriched in autoreactive B cells exhibited dose-dependent reduction of up to approximately 80%. There were no consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or platelets. Conclusions Venetoclax was generally well tolerated in women with systemic lupus erythematosus and reduced total lymphocytes and disease-relevant subsets of antigen-experienced B cells. Registration ClinicalTrials.gov: NCT01686555.

Fc gamma receptor IIIb polymorphism and systemic lupus erythematosus: association with disease susceptibility and identification of a novel FCGR3B*01 variant.

PubMed

Santos, V C; Grecco, M; Pereira, K M C; Terzian, C C N; Andrade, L E C; Silva, N P

2016-10-01

The objective of this study was to evaluate the association between Fc gamma receptor IIIb polymorphism and susceptibility to systemic lupus erythematosus and clinical traits of the disease. Genomic DNA was obtained from 303 consecutive systemic lupus erythematosus patients and 300 healthy blood donors from the southeastern region of Brazil. The polymorphic region of the FCGR3B gene was sequenced and the alleles FCGR3B*01, FCGR3B*02 and FCGR3B*03 were analyzed. The FCGR3B*01 allele was more frequent in systemic lupus erythematosus patients (43.1%) while the FCGR3B*02 allele prevailed among controls (63.7%) (P = 0.001). The FCGR3B*03 allele was found equally in both groups. The FCGR3B*01/*01 (20.7%) and FCGR3B*01/*02 (41.1%) genotypes were more frequent among systemic lupus erythematosus patients (P = 0.028 and P = 0.012, respectively) while the FCGR3B*02/*02 genotype was more frequent in controls (45.5%) (P < 0.001). One variant of the FCGR3B*01 allele previously described in Germany was found in only one control. A new variant of the FCGR3B*01 allele with two substitutions (A227G/G277A) was found in one control. Three variants of the FCGR3B*02 allele previously described in African-Americans, Brazilians, Chinese and Japanese were found in ten 10 patients and two controls. In addition, several single nucleotide polymorphisms at non-polymorphic positions were identified in both patients and controls. Susceptibility to systemic lupus erythematosus was associated with the FCGR3B*01 allele, as well as with the FCGR3B*01/*01 and FCGR3B*01/*02 genotypes. No association was found between FCGR3B genotypes and clinical manifestations, disease severity or the presence of autoantibodies. © The Author(s) 2016.

Mycophenolic acid exposure and complement fraction C3 influence inosine 5'-monophosphate dehydrogenase activity in systemic lupus erythematosus.

PubMed

Mino, Yasuaki; Naito, Takafumi; Shimoyama, Kumiko; Ogawa, Noriyoshi; Kawakami, Junichi

2017-07-01

Background Mycophenolate mofetil has recently been reported to be effective against systemic lupus erythematosus. The influence of the pharmacokinetics of mycophenolic acid, the active form of mycophenolate mofetil and the major inactive mycophenolic acid phenolic glucuronide on the activity of the target enzyme inosine 5'-monophosphate dehydrogenase, is expected to be revealed. The aim of this study was to identify the factors associated with inosine 5'-monophosphate dehydrogenase activity in systemic lupus erythematosus patients. Methods Fifty systemic lupus erythematosus patients in remission maintenance phase (29 received mycophenolate mofetil [MMF+] and 21 did not [MMF-]) were enrolled. Median and interquartile range of dose of mycophenolate mofetil were 1500 and 1000-1500 mg/day, respectively. Stepwise multiple linear regression analysis was performed to assess the dependence between inosine 5'-monophosphate dehydrogenase activity and 25 predictor values including predose plasma concentrations of free mycophenolic acid and mycophenolic acid phenolic glucuronide. Results Median and interquartile range of predose total plasma concentrations of mycophenolic acid and mycophenolic acid phenolic glucuronide were 2.73 and 1.43-5.73 and 25.5 and 13.1-54.7  µg/mL, respectively. Predose inosine 5'-monophosphate dehydrogenase activity was significantly higher in MMF+ than MMF- patients (median 38.3 and 20.6 nmoL xanthosine 5'-monophosphate/g haemoglobin/h, P<0.01). The plasma concentration of free mycophenolic acid phenolic glucuronide, complement fraction C3 and body weight were significant predictors accounting for interindividual variability in the inosine 5'-monophosphate dehydrogenase activity (adjusted R 2  = 0.52, P < 0.01) in a multivariate analysis. Conclusions Predose inosine 5'-monophosphate dehydrogenase activity was higher in systemic lupus erythematosus patients receiving mycophenolate mofetil therapy. Inosine 5'-monophosphate dehydrogenase activity may be determined by mycophenolic acid exposure and complement fraction C3 in systemic lupus erythematosus patients.

Intervention to Improve Quality of life for African-AmericaN lupus patients (IQAN): study protocol for a randomized controlled trial of a unique a la carte intervention approach to self-management of lupus in African Americans.

PubMed

Williams, Edith M; Lorig, Kate; Glover, Saundra; Kamen, Diane; Back, Sudie; Merchant, Anwar; Zhang, Jiajia; Oates, James C

2016-08-02

Systemic Lupus Erythematosus (lupus) is a chronic autoimmune disease that can impact any organ system and result in life-threatening complications. African-Americans are at increased risk for morbidity and mortality from lupus. Self-management programs have demonstrated significant improvements in health distress, self-reported global health, and activity limitation among people with lupus. Despite benefits, arthritis self-management education has reached only a limited number of people. Self-selection of program could improve such trends. The aim of the current study is to test a novel intervention to improve quality of life, decrease indicators of depression, and reduce perceived and biological indicators of stress in African-American lupus patients in South Carolina. In a three armed randomized, wait list controlled trial, we will evaluate the effectiveness of a patient-centered 'a-la-carte' approach that offers subjects a variety of modes of interaction from which they can choose as many or few as they wish, compared to a 'set menu' approach and usual care. This unique 'a-la-carte' self-management program will be offered to 50 African-American lupus patients participating in a longitudinal observational web-based SLE Database at the Medical University of South Carolina. Each individualized intervention plan will include 1-4 options, including a mail-delivered arthritis kit, addition and access to an online message board, participation in a support group, and enrollment in a local self-management program. A 'set menu' control group of 50 lupus patients will be offered a standardized chronic disease self-management program only, and a control group of 50 lupus patients will receive usual care. Outcomes will include changes in (a) health behaviors, (b) health status, (c) health care utilization, and (d) biological markers (urinary catecholamines). Such a culturally sensitive educational intervention which includes self-selection of program components has the potential to improve disparate trends in quality of life, disease activity, depression, and stress among African-American lupus patients, as better outcomes have been documented when participants are able to choose/dictate the content and/or pace of the respective treatment/intervention program. Since there is currently no "gold standard" self-management program specifically for lupus, this project may have a considerable impact on future research and policy decisions. NCT01837875 ; April 18, 2013.

Lupus erythematosus cells in bone marrow: the only clue to a previously unsuspected diagnosis of systemic lupus erythematosus.

PubMed

Pujani, Mukta; Kushwaha, Shivani; Sethi, Neha; Beniwal, Anu; Shukla, Shailaja

2013-01-01

Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease characterized by the development of antinuclear antibodies. Nowadays considered outdated, lupus erythematosus (LE) cell preparation served as a screening test for SLE for decades. However, the importance of discovering LE cells on routine cytology cannot be overemphasized. We report the case of a 30-year-old female in whom bone marrow aspiration (BMA) was performed during an investigative workup for pyrexia of unknown origin. The observation of LE cells in direct bone marrow smears (without the use of an anticoagulant) raised the suspicion of SLE, which was later confirmed by antinuclear antibody testing. In the present case, LE cells were observed on BMA performed for the investigation of fever of unknown origin. The unexpected observation of LE cells in BMA smears emphasizes the fact that good morphological observation of marrow aspirates can provide crucial clues to a previously unsuspected diagnosis.

Radiologic findings in late-onset systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braunstein, E.M.; Weissman, B.N.; Sosman, J.L.

1983-03-01

Systemic lupus erythematosus in the elderly has a different clinical and serologic course from that in young patients. Radiographic findings in patients in whom the diagnosis was made after age 50 were compared with findings in younger patients to see if the radiologic patterns are also different. The only significant radiographic difference between the two groups was that the older group had a greater incidence of soft-tissue swelling of the hands and wrists (p < 0.001). There was no significant difference in osteopenia, erosion, soft-tissue calcification, alignment abnormalities, or intrathoracic findings. Of 24 patients over age 50, two developed lymphomamore » and another developed multiple myeloma. The data agree with clinical observations that there is a higher incidence of arthritis in late-onset lupus, but clinical findings of increased incidence of pleuropericardial disease are not confirmed radiographically. The coincidence of hematologic malignancy with late-onset lupus in this series is noteworthy.« less

Insights Gained From the Study of Pediatric Systemic Lupus Erythematosus.

PubMed

Lo, Mindy S

2018-01-01

The pathophysiology of systemic lupus erythematosus (SLE) has been intensely studied but remains incompletely defined. Currently, multiple mechanisms are known to contribute to the development of SLE. These include inadequate clearance of apoptotic debris, aberrant presentation of self nucleic antigens, loss of tolerance, and inappropriate activation of T and B cells. Genetic, hormonal, and environmental influences are also known to play a role. The study of lupus in children, in whom there is presumed to be greater genetic influence, has led to new understandings that are applicable to SLE pathophysiology as a whole. In particular, characterization of inherited disorders associated with excessive type I interferon production has elucidated specific mechanisms by which interferon is induced in SLE. In this review, we discuss several monogenic forms of lupus presenting in childhood and also review recent insights gained from cytokine and autoantibody profiling of pediatric SLE.

Acute macular neuroretinopathy associated with systemic lupus erythematosus.

PubMed

Lee, D H; Lee, S C; Kim, M

2016-04-01

Acute macular neuroretinopathy (AMN) is a rare disorder that presents with abrupt visual change with wedge-shaped or flower-like lesions pointing towards the fovea. Ischemic insults to the retinal capillary plexus may be important for development of this disease. While many case reports have been published on AMN, none have described AMN in association with systemic lupus erythematosus (SLE). Here, we report a case of AMN associated with newly-diagnosed SLE. We speculate that in patients with lupus flares, immune complex-mediated vascular injury and microvascular thrombosis may disrupt the deep retinal capillary network, causing ischemic damages to the outer retina and leading to the development of AMN. AMN can develop in patients with lupus flares, and must be considered as an SLE-associated ophthalmologic complication. To the best of our knowledge, this is the first case report of AMN associated with SLE. © The Author(s) 2015.

Childhood lupus nephritis: 12 years of experience from a developing country's perspective.

PubMed

Samanta, Moumita; Nandi, Madhumita; Mondal, Rakesh; Hazra, Avijit; Sarkar, Sumatra; Sabui, Tapas; Kundu, Chanchal Kumar; Biswas, Arnab

2017-09-01

To assess the long-term outcome of lupus nephritis in children with systemic lupus erythematosus followed up over 12 years at a tertiary care teaching hospital in Eastern India. This is a retrospective observational study of the clinicopathological presentation, management, and outcome in 46 children with lupus nephritis over a period of 12 years at a tertiary teaching hospital in Eastern India. Mortality was compared between different lupus classes and therapy groups with Kaplan-Meier analysis and log-rank test. The incidence of lupus nephritis was 58.97% [95% confidence interval (CI) 48.06%-59.89%] with the mean age at presentation being 10.2±2.43 years (range 5.5-14.5) years. Majority belonged to class IV (30.43%), followed by class II (26.91%), class III (23.91), and class V (8.70%). Outcome analysis of children with lupus nephritis over 12 years revealed that 24 (52.17%) achieved complete remission of disease activity, 5 attained partial remission, 4 continued to have active disease, 5 developed end-stage renal disease (ESRD), and 8 died. Overall mortality thus observed was 17.39% with septicemia in the background of ESRD being the commonest cause. No significant difference in mortality was observed between different lupus nephritis classes or therapy arm groups. The study throws light on various aspects of lupus nephritis and their long-term outcome patterns in children from developing countries such as India.

Characterization of inflammatory markers associated with systemic lupus erythematosus patients undergoing treatment.

PubMed

Timóteo, Rodolfo Pessato; Micheli, Douglas Cobo; Teodoro, Reginaldo Botelho; Freire, Marlene; Bertoncello, Dernival; Murta, Eddie Fernando Candido; Tavares-Murta, Beatriz Martins

To characterize the inflammatory profiles of patients with systemic lupus erythematosus receiving standard treatment compared to healthy controls. Peripheral venous blood was collected from systemic lupus erythematosus patients (n=14) and controls (n=18) at enrollment. Blood samples were used for quantification, by flow cytometry, of CD11b (integrin) and Chemokine receptor CXCR2 expression surface antigen in neutrophils and lymphocytes, while cytokines were assayed in serum samples. Purified neutrophils were assayed by their ability to phagocytize human plasma-opsonized zymosan. Patients had a median (interquartile range) disease activity index of 1.0 (0-2.0) characteristic of patients in remission. Interleukin-6 and interleukin-10 serum concentrations were significantly higher in the patient group compared to controls and the phagocytic index of circulating neutrophils was significantly reduced in patients compared to controls. The levels of interleukin-2, interleukin-5, interleukin-8 and tumor necrosis factor alpha did not significantly differ between patients and controls. Flow cytometric analysis revealed that the integrin expression levels were reduced in lymphocytes (but not in neutrophils) obtained from systemic lupus erythematosus patients, while surface expression of the chemokine receptor 2 was similar in both neutrophils and lymphocytes. Systemic lupus erythematosus patients receiving standard treatment presented with elevated systemic levels of interleukin-6 and interleukin-10, reduced neutrophil phagocytic capacity, and reduced lymphocyte expression of integrin even when symptoms were in remission. These alterations to innate immune components may put these individuals at a greater risk for acquiring infections. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Pregnancy and renal outcomes in lupus nephritis: an update and guide to management.

PubMed

Bramham, K; Soh, M C; Nelson-Piercy, C

2012-10-01

Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age, and advances in treatment have resulted in an increasing number of women with renal involvement becoming pregnant. Knowledge of the relationship of the condition with respect to fertility and pregnancy is important for all clinicians involved in the care of women with lupus nephritis because they have complicated pregnancies. Presentation of lupus nephritis can range from mild asymptomatic proteinuria to rapidly progressive renal failure and may occur before, during, or after pregnancy. The timing of diagnosis may influence pregnancy outcome. Pregnancy may also affect the course of lupus nephritis. All pregnancies in women with lupus nephritis should be planned, preferably after more than six-months of quiescent disease. Predictors of poor obstetric outcome include active disease at conception or early pregnancy, baseline poor renal function with Creatinine >100 μmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid syndrome and hypertension. In this review the most recent studies of pregnancies in women with lupus nephritis are discussed and a practical approach to managing women prepregnancy, during pregnancy and post-partum is described.

Sunlight Triggers Cutaneous Lupus through a Colony Stimulating Factor-1 (CSF-1) Dependent Mechanism in MRL-Faslpr mice

PubMed Central

Menke, Julia; Hsu, Mei-Yu; Byrne, Katelyn T.; Lucas, Julie A.; Rabacal, Whitney A.; Croker, Byron P.; Zong, Xiao-Hua; Stanley, E. Richard; Kelley, Vicki R.

2008-01-01

Sunlight (UVB) triggers cutaneous (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mø) -mediated mechanism in MRL-Faslpr mice. By constructing mutant MRL-Faslpr strains expressing varying levels of CSF-1 (high, intermediate, none), and use of an ex-vivo gene transfer to deliver CSF-1 intra-dermally, we determined that CSF-1 induces CLE in lupus-susceptible, MRL-Faslpr mice, but not in lupus-resistant, BALB/c mice. Notably, UVB incites an increase in Mø, apoptosis in the skin and CLE in MRL-Faslpr, but not in CSF-1-deficient MRL-Faslpr mice. Furthermore, UVB did not induce CLE in BALB/c mice. Probing further, UVB stimulates CSF-1 expression by keratinocytes leading to recruitment and activation of Mø that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mø-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL-Faslpr, but not lupus-resistant BALB/c mice. Taken together, we envision CSF-1 as the “match” and lupus-susceptibility as the “tinder” leading to CLE. PMID:18981160

PREVENTING AUTOIMMUNITY PROTECTS AGAINST THE DEVELOPMENT OF HYPERTENSION AND RENAL INJURY

PubMed Central

Mathis, Keisa W.; Wallace, Kedra; Flynn, Elizabeth R.; Maric-Bilkan, Christine; LaMarca, Babbette; Ryan, Michael J.

2015-01-01

Several studies suggest a link between autoimmunity and essential hypertension in humans. However, whether autoimmunity can drive the development of hypertension remains unclear. The autoimmune disease systemic lupus erythematosus is characterized by autoantibody production and the prevalence of hypertension is markedly increased in this patient population compared to normal healthy women. We hypothesized that preventing the development of autoimmunity would prevent the development of hypertension in a mouse model of lupus. Female lupus (NZBWF1) and control mice (NZW) were treated weekly with anti-CD20 or IgG antibodies (both 10 mg/kg, IV) starting at 20 weeks of age for 14 weeks. Anti-CD20 therapy markedly attenuated lupus disease progression as evidenced by reduced CD45R+ B cells and lower double-stranded DNA autoantibody activity. In addition, renal injury in the form of urinary albumin, glomerulosclerosis, and tubulointerstitial fibrosis, as well as tubular injury (indicated by renal cortical expression of neutrophil gelatinase-associated lipocalin) was prevented by anti-CD20 therapy in lupus mice. Finally, lupus mice treated with anti-CD20 antibody did not develop hypertension. The protection against the development of hypertension was associated with lower renal cortical tumor necrosis factor-α expression, a cytokine that has been previously reported by us to contribute to the hypertension in this model, as well as renal cortical monocyte chemoattractant protein -1 expression and circulating T cells. These data suggest that the development of autoimmunity and the resultant increase in renal inflammation is an important underlying factor in the prevalent hypertension that occurs during systemic lupus erythematosus. PMID:25024282

IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production

PubMed Central

Lech, Maciej; Weidenbusch, Marc; Kulkarni, Onkar P.; Ryu, Mi; Darisipudi, Murthy Narayana; Susanti, Heni Eka; Mittruecker, Hans-Willi; Mak, Tak W.

2011-01-01

The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells. PMID:21742731

Pneumocystis jirovecii pneumonia in systemic lupus erythematosus from southern Taiwan.

PubMed

Weng, Chia-Tse; Liu, Ming-Fei; Weng, Meng-Yu; Lee, Nan-Yao; Wang, Ming-Chang; Lin, Wei-Chieh; Ou, Chih-Ying; Lai, Wu-Wei; Hsu, Shiang-Chin; Chao, Sheau-Chiou; Chung, Ta-Jung; Lee, Chung-Ta; Shieh, Chi-Chang; Wang, Jiu-Yao; Wang, Chrong-Reen

2013-08-01

Opportunistic infection has been documented in systemic lupus erythematosus with special attention paid to Pneumocystis jirovecii because of the significant morbidity and high mortality. The limited large-scale investigations covering P. jirovecii pneumonia (PCP) in systemic lupus erythematosus following biologics or immunosuppressants therapy prompted us to perform this study in southern Taiwan. A retrospective study was completed in 858 hospitalized lupus patients from January 2000 to December 2011. The definite diagnosis of PCP was made by the laboratory detection of Pneumocystis organisms together with consistent clinical and radiological manifestations of PCP. Positive polymerase chain reaction results of sputum samples were not regarded as infection in this study, unless P. jirovecii was the sole pathogen found and pulmonary manifestations resolved following antibiotics for PCP treatment alone. The laboratory identification of Pneumocystis organisms depended on lung biopsy in 2 cases and bronchoalveolar lavage in 3 patients. Five cases, 2 women and 3 men aged 30 to 50 years (41.8 ± 8.8 years), were identified with a 0.6% incidence. None received chemoprophylactics against P. jirovecii infection. All had lupus nephritis and lymphopenia with low CD4 T-cell counts. Prior usages of higher daily prednisolone dosages and concomitant biologics or immunosuppressants were observed in all patients. Pneumocystis jirovecii pneumonia contributed to a high mortality rate (60%). We report the rare occurrence but high mortality of PCP infection in this study. A consensus guideline addressing prophylactic antibiotics against Pneumocystis organisms in highest-risk lupus patients on biologics or immunosuppressants could be helpful in guiding their management.

Macrophage activation syndrome as the initial manifestation of severe juvenile onset systemic lupus erythematosus. Favorable response to cyclophosphamide.

PubMed

Torres Jiménez, Alfonso; Solís Vallejo, Eunice; Zeferino Cruz, Maritza; Céspedes Cruz, Adriana; Sánchez Jara, Berenice

2014-01-01

The macrophage activation syndrome is a rare but potentially fatal complication of patients with autoimmune rheumatic diseases. This is a clinicopathological entity characterized by activation of histiocytes with prominent hemophagocytosis in the bone marrow and other reticuloendothelial systems. In patients with lupus it may mimic an exacerbation of the disease or infection. We report the case of a 7-year-old girl in whom the diagnosis of lupus erythematosus and macrophage activation syndrome was simultaneously made with response to the use of cyclophosphamide. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Systemic lupus erythematosus and thrombotic thrombocytopenia purpura: a refractory case without lupus activity.

PubMed

Garcia Boyero, Raimundo; Mas Esteve, Eva; Mas Esteve, Maria; Millá Perseguer, M Magdalena; Marco Buades, Josefa; Beltran Fabregat, Juan; Cañigral Ferrando, Guillermo; Belmonte Serrano, Miguel Angel

2013-01-01

The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Current Concepts in Dermatology

PubMed Central

Jackson, Robert

1963-01-01

Many systemic diseases have cutaneous manifestations. In some diseases skin involvement is the predominant factor (Behçet's syndrome, urticaria pigmentosa, discoid lupus erythematosus and pseudoxanthoma elasticum); in others the skin manifestations, when present, are an important part of the condition (sarcoidosis, systemic lupus erythematosus, hypersensitivity angiitis, porphyria). This report includes descriptions of and comments on these cutaneous manifestations. Erythema nodosum and erythema multiforme are reaction patterns of the skin and mucous membrane which may have many causes. The relationship between discoid and systemic lupus erythematosus is discussed. There is little doubt that these are variations of the same basic disease process, even though the prognoses are very different. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:14063940

Causes and predictors of mortality in hospitalized lupus patient in Sarawak General Hospital, Malaysia.

PubMed

Teh, C L; Ling, G R

2013-01-01

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can be life threatening and fatal if left untreated. Causes and prognostic indicators of death in SLE have been well studied in developed countries but lacking in developing countries. We aimed to investigate the causes of mortality in hospitalized patients with SLE and determine the prognostic indicators of mortality during hospitalization in our center. All SLE patients who were admitted to Sarawak General Hospital from January 1, 2006 to December 31, 2010, were followed up in a prospective study using a standard protocol. Demographic data, clinical features, disease activities and damage indices were collected. Logistic regression and Cox regression analysis were used to determine the prognostic indicators of mortality in our patients. There were a total of 251 patients in our study, with the female to male ratio 10 to 1. Our study patients were of multiethnic origins. They had a mean age of 30.5 ± 12.2 years and a mean duration of illness of 36.5 ± 51.6 months. The main involvements were hematologic (73.3%), renal (70.9%) and mucocutaneous (67.3%). There were 26 deaths (10.4%), with the main causes being: infection and flare (50%), infection alone (19%), flare alone (19%) and others (12%). Independent predictors of mortality in our cohort of SLE patients were the presence of both infection and flare of disease (hazard ratio (HR) 5.56) and high damage indices at the time of admission (HR 1.91). Infection and flare were the main causes of death in hospitalized Asian patients with SLE. The presence of infection with flare and high damage indices at the time of admission were independent prognostic indicators of mortality.

Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus Erythematosus: The Role of the Extrapituitary Prolactin Promoter Polymorphism at -1149G/T.

PubMed

Treadwell, Edward L; Wiley, Kenneth; Word, Beverly; Melchior, William; Tolleson, William H; Gopee, Neera; Hammons, George; Lyn-Cook, Beverly D

2015-01-01

Systemic lupus erythematosus (SLE) has shown an association with high levels of prolactin, low levels of dehydroepiandrosterone (DHEA), and induction of inflammatory cytokines in the serum of patients with the disease. This preliminary study examined the relevance of a -1149G/T functional single-nucleotide polymorphism (SNP) (rs1341239) in the promoter of the extrapituitary prolactin gene in a cohort of African American and European American women with lupus. Examination of this SNP revealed that the -1149TT genotype was correlated with higher levels of prolactin in serum and prolactin gene expression (p = 0.0001) in peripheral blood mononuclear cells (PBMCs). Lower levels of DHEA in serum were demonstrated in lupus patients (p = 0.001); those with the -1149TT genotype had the lowest levels of DHEA. Furthermore, a small subset of women who were on DHEA therapy and had a TT genotype showed a significant decrease in prolactin gene expression and lower disease activity scores (SLEDAI). Lupus patients, particularly African Americans, had significantly higher levels of IL-6 (p = 0.0001) and TNF-α (p = 0.042). This study suggests that the -1149TT genotype may be a risk factor for lupus and may predict who could possibly benefit from DHEA therapy; therefore, these results should be validated in a larger cohort with all ethnic groups.

Is systemic lupus erithematosus a new risk factor for atherosclerosis?

PubMed

Freire, Beatriz Funayama Alvarenga; da Silva, Rogério Cardoso; Fabro, Alexandre Todorovic; dos Santos, Daniela Cristina

2006-09-01

To evaluate the prevalence of cardiovascular events (CVE) secondary to atherosclerosis in lupus patients and correlate them to the traditional risk factors, disease duration and drug therapy used. A retrospective study was carried out based on data obtained from patients charts. Patients included were those who had a lupus diagnosis confirmed at least two years before inclusion in the study and had been followed since 1992. CVE were characterized as MI, angina pectoris and stroke non-related to lupus activity. Risk factors and drugs used for treatment were recorded. Seventy-one charts were analyzed. Patients mean age was 34.2+/-12.7 years; 68 were women and three were men; 58 were Caucasian (81.6%). Ten (14.08%) presented CVE. Patients in whom CVE were observed were older (42.7 vs. 32.8 years p=0.0021) and presented longer disease duration (10.8 vs. 7.2 years p=0.011). The traditional risk factors, daily and cumulative doses of steroids, immunosuppressive drugs and antimalarial drugs were not significant when patients with and without CVE were compared. The prevalence of CVE secondary to atherosclerosis in systemic lupus erythematosus (SLE) was 14.08%. The traditional risk factors were not associated with the development of CVE in lupus patients. Patients that presented cardiovascular events were older and presented longer disease duration. It is a premature conclusion to establish SLE as an independent risk factor for atherosclerosis development.

Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients.

PubMed

Perazzio, Sandro Félix; Silva, Neusa Pereira da; Carneiro-Sampaio, Magda; Andrade, Luis Eduardo Coelho

2016-01-01

The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and ≥500μg/L), moderate (<500 and ≥100μg/L) or severe (<100μg/L). SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

The incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus in New Zealand Maori and Pacific Island children: the Starship experience (2000-2010).

PubMed

Concannon, A; Rudge, S; Yan, J; Reed, P

2013-10-01

To describe the incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus (jSLE) in a cohort of New Zealand Maori and Pacific Island children compared to European children. A chart review was conducted of children with jSLE seen by the Starship paediatric rheumatology and/or renal services between January 2000 and November 2010. Diagnostic clinical data and lupus nephritis data at anytime were collated while classic British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were derived retrospectively. Thirty-two children were diagnosed with jSLE with an annual incidence of 0.52 per 100,000 per year. Compared with European children (0.31 per 100,000 per year) the incidence of jSLE was higher among Maori and Pacific (0.67 per 100,000 per year, p=0.06) and significantly higher among Asian children (1.17 per 100,000 per year, p=0.01). Compared with European children, Maori and Pacific children were more frequently diagnosed with lupus nephritis (80% vs 40%, p=0.09) and severe (WHO class 4 or 5) renal lesions (60% vs 40%, p=0.43) at presentation. Similarly, at any time during the study, lupus nephritis (100% vs 40%, p=0.001) and severe (WHO class 4 or 5) renal lesions (73.3% vs 40%, p=0.12) were more frequent among Maori and Pacific compared with European children. Furthermore, retrospective BILAG assessment of diagnostic disease severity demonstrated that Maori and Pacific children experienced the majority of severe "Category A" disease (56.8% vs 22.7%, p=0.17) which was predominantly renal (73.3% vs 40%, p=0.12) in nature. This is the first description of the incidence and clinical manifestations of jSLE in a cohort of New Zealand children. Although limited by the small numbers involved it confirmed anecdotal suspicions that the incidence of jSLE among Maori, Pacific and Asian children is higher than European children. Lupus nephritis is also more frequent and severe in Maori and Pacific children.

Modulating proximal cell signaling by targeting Btk ameliorates humoral autoimmunity and end-organ disease in murine lupus.

PubMed

Hutcheson, Jack; Vanarsa, Kamala; Bashmakov, Anna; Grewal, Simer; Sajitharan, Deena; Chang, Betty Y; Buggy, Joseph J; Zhou, Xin J; Du, Yong; Satterthwaite, Anne B; Mohan, Chandra

2012-11-08

Systemic lupus erythematosus is a chronic autoimmune disease characterized by an abundance of autoantibodies against nuclear antigens. Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity. The aim of this study was to determine the effect of Btk inhibition by PCI-32765 on the development of lupus in lupus-prone B6.Sle1 and B6.Sle1.Sle3 mice. B6.Sle1 or B6.Sle1.Sle3 mice received drinking water containing either the Btk inhibitor PCI-32765 or vehicle for 56 days. Following treatment, mice were examined for clinical and pathological characteristics of lupus. The effect of PCI-32765 on specific cell types was also investigated. In this study, we report that Btk inhibition dampens humoral autoimmunity in B6.Sle1 monocongenic mice. Moreover, in B6.Sle1.Sle3 bicongenic mice that are prone to severe lupus, Btk inhibition also dampens humoral and cellular autoimmunity, as well as lupus nephritis. These findings suggest that partial crippling of cell signaling in B cells and antigen presenting cells (APCs) may be a viable alternative to total depletion of these cells as a therapeutic modality for lupus.

Treatment of coexistent psoriasis and lupus erythematosus.

PubMed

Varada, Sowmya; Gottlieb, Alice B; Merola, Joseph F; Saraiya, Ami R; Tintle, Suzanne J

2015-02-01

The coexistence of psoriasis and lupus erythematosus (LE) is rare. Anecdotal evidence suggests that anti-tumor necrosis factor alfa (TNF-α) agents may be efficacious in LE, although their use is commonly avoided in this disease because of concern for lupus flare. We sought to describe the epidemiology, serologic findings, and therapeutic choices in patients with coexistent psoriasis/psoriatic arthritis and LE and to determine the risk of lupus flares with TNF-α inhibitors. We performed a retrospective multicenter study of patients given the diagnoses of psoriasis (or psoriatic arthritis) and lupus erythematosus (systemic LE or cutaneous LE, including either subacute cutaneous LE or discoid LE) at 2 academic tertiary-care centers. A total of 96 patients with a mean age of 56 years was included. We report higher-than-expected rates of white race and psoriatic arthritis. One clinical lupus flare was observed in a patient receiving a TNF-α inhibitor, resulting in an incidence of 0.92% lupus flares per patient-year of TNF-α inhibitor use. Retrospective chart review, small sample size, and limited documentation. Anti-TNF-α agents, ustekinumab, and abatacept may be valid treatment options for patients with concomitant LE and psoriasis. Clinical lupus flares in LE patients treated with TNF-α inhibitors were infrequent. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Decreased interleukin 35 and CD4+EBI3+ T cells in patients with active systemic lupus erythematosus.

PubMed

Ouyang, Han; Shi, Yong-Bing; Liu, Zhi-Chun; Wang, Zhi; Feng, Sheng; Kong, Shu-Min; Lu, Ying

2014-08-01

Interleukin 35 (IL-35) is likely to contribute to the development of autoimmune diseases, as the Epstein-Barr virus-induced gene protein 3 (EBI3) is the specificity subunit of IL-35. Nevertheless, until recently, no studies have evaluated its role in systemic lupus erythematosus (SLE) in humans. The objective of this study was to investigate the serum IL-35 level and the percentage of CD4EBI3 T cells in the peripheral blood of patients with SLE and explore the roles of double-positive T cells and IL-35 in the pathogenesis of SLE and the effects of glucocorticoid on these roles. Fifty-five hospitalized patients with SLE were recruited, and 20 volunteers were enrolled as healthy controls. Serum IL-35 levels were measured by enzyme-linked immunosorbent assay, and the percentage of CD4EBI3 T cells was analyzed by flow cytometry. The serum IL-35 level and the percentage of CD4EBI3 T cells were significantly decreased in patients with active SLE compared with healthy controls and patients with inactive SLE. The serum IL-35 level and the percentage of CD4EBI3 T cells were negatively correlated with the SLE disease activity index. The percentages of CD4EBI3 T cells and serum IL-35 levels in 10 untreated patients with active SLE were increased at days l, 3, and 7 after the treatment with methylprednisolone (0.8 mg·kg·d) compared with the percentages before the treatment. These results demonstrate that abnormalities in IL-35 and CD4EBI3 T cells may play important roles in the pathogenesis of SLE; the percentage of double-positive T cells and the level of IL-35 are parameters for the evaluation of SLE activity and severity.

C1q complement component and -antibodies reflect SLE activity and kidney involvement.

PubMed

Horák, P; Hermanová, Z; Zadrazil, J; Ciferská, H; Ordeltová, M; Kusá, L; Zurek, M; Tichý, T

2006-07-01

The role of the complement system in the pathogenesis of systemic diseases is very ambivalent. In systemic lupus erythematosus (SLE), many abnormalities in the activation of the complement system have been reported. The most important antibodies formed against the complement system in SLE are the ones associated with the C1q component. The aim of this study was to assess separately the anti-C1q antibodies and C1q component in the serum from 65 patients with SLE, then in individuals with (n=33) and without (n=32) lupus nephritis and with active (n=36) and nonactive (n=29) form of the disease (European Consensus Lupus Activity Measurement, ECLAM>3, ECLAM

Invasive aspergillosis associated with systemic lupus erythematosus and cardiac postoperative complication

PubMed Central

Macêdo, Danielle Patrícia Cerqueira; Silva-Júnior, Heraldo Maia; de Souza-Motta, Cristina Maria; Milan, Eveline Pípolo; Neves, Rejane Pereira

2009-01-01

Aspergillus is a ubiquitous fungus which can cause a variety of clinical syndromes. This fungus has emerged as agent of systemic infections and has therefore gained considerable public health importance. This paper describes two cases of invasive aspergillosis caused by A. fumigatus in immuno-suppressed patients and underscores the importance of early identification of Aspergillus infection associated with systemic lupus erythematosus and cardiac postoperative complications. PMID:24031340

Intravenous Immunoglobulin in the Management of Lupus Nephritis

PubMed Central

Wenderfer, Scott E.; Thacker, Trisha

2012-01-01

The occurrence of nephritis in patients with systemic lupus erythematosus is associated with increased morbidity and mortality. The pathogenesis of lupus nephritis is complex, involving innate and adaptive cellular and humoral immune responses. Autoantibodies in particular have been shown to be critical in the initiation and progression of renal injury, via interactions with both Fc-receptors and complement. One approach in the management of patients with lupus nephritis has been the use of intravenous immunoglobulin. This therapy has shown benefit in the setting of many forms of autoantibody-mediated injury; however, the mechanisms of efficacy are not fully understood. In this paper, the data supporting the use of immunoglobulin therapy in lupus nephritis will be evaluated. In addition, the potential mechanisms of action will be discussed with respect to the known involvement of complement and Fc-receptors in the kidney parenchyma. Results are provocative and warrant additional clinical trials. PMID:23056926

Predictors of kidney biopsy complication among patients with systemic lupus erythematosus.

PubMed

Chen, T K; Estrella, M M; Fine, D M

2012-07-01

Kidney biopsy is essential for the diagnosis and management of lupus nephritis. The risk of bleeding complication, however, is not defined in the systemic lupus erythematosus population. A retrospective cohort study was conducted to determine predictors of major and minor complications among patients with systemic lupus erythematosus undergoing percutaneous ultrasound-guided kidney biopsy. Major complications included bleeding necessitating intervention, hypotension requiring vasopressors or higher level of care or death. Minor complications included moderate or large (≥ 4 cm in largest diameter) perinephric hematoma, gross hematuria or voiding difficulties. All patients were observed for at least 23 h post-procedure. The overall incidence of bleeding was 10.5% (2.7% major, 7.8% minor). Adjusted logistic regression showed that for every 10,000 cells/mm(3) decrease in platelet count, risk for major and any complication increased by 27% (odds ratio 1.27; 95% confidence intervals 1.06-1.51; p = 0.01) and 8% (odds ratio 1.08; 95% confidence intervals 1.02-1.15; p = 0.01), respectively. Patients with a platelet count <150,000 cells/mm(3) were 30 times more likely to experience a major complication (p = 0.002). Other candidate predictors, including steroid exposure, kidney function, hematocrit and histopathology, were not significant. Kidney biopsies are well tolerated in patients with systemic lupus erythematosus. However, patients with pre-biopsy platelet counts <150,000 cells/mm(3) are at markedly increased risk for a major bleeding complication.

Mycophenolate mofetil as maintenance therapy for childhood-onset systemic lupus erythematosus patients with severe lupus nephritis.

PubMed

Kizawa, Toshitaka; Nozawa, Tomo; Kikuchi, Masako; Nagahama, Kiyotaka; Okudela, Koji; Miyamae, Takako; Imagawa, Tomoyuki; Nakamura, Tomoko; Mori, Masaaki; Yokota, Shumpei; Tsutsumi, Hiroyuki

2015-03-01

We evaluated histological changes occurring in renal biopsy specimens, between the time before initial induction therapy and after 12 months' maintenance therapy, as well as changes in laboratory parameters, SLE disease activity (SLEDAI), and dosage of corticosteroid (CS) in childhood-onset systemic lupus erythematosus (SLE) patients treated with mycophenolate mofetil (MMF). A retrospective analysis was performed on nine patients diagnosed with childhood-onset SLE and lupus nephritis. They were treated with pulsed mPSL and intravenous cyclophosphamide as induction therapy and MMF (500-1500 mg/day) plus CS as maintenance therapy. Renal biopsy was performed before the initial induction therapy and after 12 months' maintenance therapy. Pathological findings at second biopsy were improved in eight of nine patients (89%). The findings of SLEDAI, urinalysis, and blood tests also showed improvement. CS doses could be tapered satisfactorily. Adverse events were observed in two patients. No patients treated with MMF experienced any disease flares during maintenance therapy. MMF as maintenance therapy might be useful in that not only the histological findings of lupus nephritis were improved, but also CS doses could be beneficially tapered. Nonetheless, this is a retrospective report of only nine cases and further prospective multicenter studies are necessary.

Lupus Panniculitis as an Initial Manifestation of Systemic Lupus Erythematosus: A Case Report.

PubMed

Zhao, Yu-Kun; Wang, Fang; Chen, Wen-Na; Xu, Rui; Wang, Zhuo; Jiang, Yuan-Wen; Luo, Di-Qing; Han, Jian-De

2016-04-01

Lupus erythematosus panniculitis (LEP) is a variant of chronic cutaneous lupus erythematosus (CCLE). Reported cases of LEP lesions before the diagnosis of systemic lupus erythematosus (SLE) were very rare; only 9 cases have been reported, to the best of our knowledge. We now describe the case of a 19-year-old male patient, with an overall review of the English literature. In the earliest stage of the present case, nodules and ulcers involved his left leg and face, with no other accompanied symptoms. The skin lesions disappeared after treatment with methylprednisolone, 16 mg/d for 1 month. Seven months after discontinuing methylprednisolone, the cutaneous nodules and ulcers on his back recurred and were accompanied by fever, hair loss, and polyarthritis. Blood tests revealed leucopenia, positive antinuclear antibody and Smith antibody, and proteinuria. Histopathological findings were most consistent with LEP. This was followed sequentially by the diagnosis of SLE. The patient improved again after treatment with methylprednisolone and cyclophosphamide.Patients with LEP should have regular follow-ups because the development of SLE is possible. Early diagnosis and proper treatment is pivotal to improve the prognosis of such patients.

Detection of lupus erythematosus cells in pleural effusion: An unusual presentation of systemic lupus erythematosus.

PubMed

Gulhane, Sushma; Gangane, Nitin

2012-01-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease typically diagnosed by a combination of physical findings and clinical laboratory testing. Several decades ago, the diagnosis of lupus included the lupus erythematosus (LE) cell assay. SLE is associated with pleuropulmonary manifestations in well over 50% of cases. Although pleural effusion is common but very rarely is the initial manifestation of disease. There are very few reports of SLE diagnosed in a cytopathology laboratory. We report an unusual case of SLE in a 16-year-old female who presented with acute shortness of breath, fever and cough. Her chest radiograph showed bilateral pleural effusion. This effusion was tapped and sent to the cytopathology laboratory. The cytological examination of the pleural fluid revealed numerous LE cells and led to the diagnosis of SLE. Autoimmune serology techniques such as anti-nuclear antibody staining have replaced the LE cell assay. However, as presented in this report and found in a review of the literature, the in vivo finding of LE cells by cytopathology can provide an important clue to the diagnosis of SLE, especially when associated with an uncommon presentation.

Associated Variables of Myositis in Systemic Lupus Erythematosus: A Cross-Sectional Study.

PubMed

Liang, Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2017-05-26

BACKGROUND This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). MATERIAL AND METHODS Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). RESULTS The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. CONCLUSIONS The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients.

Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials.

PubMed

Manzi, Susan; Sánchez-Guerrero, Jorge; Merrill, Joan T; Furie, Richard; Gladman, Dafna; Navarra, Sandra V; Ginzler, Ellen M; D'Cruz, David P; Doria, Andrea; Cooper, Simon; Zhong, Z John; Hough, Douglas; Freimuth, William; Petri, Michelle A

2012-11-01

To evaluate the effects of belimumab versus placebo, plus standard systemic lupus erythematosus (SLE) therapy, on organ domain-specific SLE disease activity. Data obtained after 52 weeks of treatment from two phase III trials (BLISS-52 and BLISS-76) comparing belimumab 1 and 10 mg/kg versus placebo, plus standard therapy, in 1684 autoantibody-positive patients were analysed post hoc for changes in British Isles Lupus Assessment Group (BILAG) and Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ domain scores. At baseline, the domains involved in the majority of patients were musculoskeletal and mucocutaneous by both BILAG and SELENA-SLEDAI, and immunological by SELENA-SLEDAI. At 52 weeks, significantly more patients treated with belimumab versus placebo had improvement in BILAG musculoskeletal and mucocutaneous domains (1 and 10 mg/kg), and in SELENA-SLEDAI mucocutaneous (10 mg/kg), musculoskeletal (1 mg/kg) and immunological (1 and 10 mg/kg) domains. Improvement was also observed in other organ systems with a low prevalence (≤16%) at baseline, including the SELENA-SLEDAI vasculitis and central nervous system domains. Significantly fewer patients treated with belimumab versus placebo had worsening in the BILAG haematological domain (1 mg/kg) and in the SELENA-SLEDAI immunological (10 mg/kg), haematological (10 mg/kg) and renal (1 mg/kg) domains. Belimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains. Less worsening occurred in the haematological, immunological and renal domains.

Neuropsychiatric manifestations and associated autoantibodies in systemic lupus erythematosus patients from Western India.

PubMed

Pradhan, Vandana; Patwardhan, Manisha; Rajadhyaksha, Anjali; Dhawale, Nivedita; Ghosh, Kanjaksha

2015-03-01

Systemic lupus erythematosus with neuropsychiatric involvement (NPSLE) can be diagnosed clinically, but there is no definite serological biomarker established. The objectives of this study were to evaluate the neuropsychiatric involvement in systemic lupus erythematosus (SLE) patients and to detect the autoantibodies associated with them. Sixty NPSLE patients along with sixty SLE patients without neuropsychiatric involvement from Maharashtra, India, were included. All patients were clinically diagnosed using the American College of Rheumatology criteria. Disease activity was assessed using the systemic lupus erythematosus disease activity index. Antinuclear antibodies (ANA), anti-dsDNA, anti-neuronal antibodies were detected by indirect immunofluorescence test. Anti-ribosomal antibodies (anti-Rib-P) were tested by ELISA. NPSLE was diagnosed in age group ranging between 10 and 20 years compared with SLE patients without neuropsychiatric involvement (21-30 years). The most frequent symptoms were psychosis (75%), followed by seizures (58%), lupus headache (40%), cognitive dysfunction (36%), mood disorder (30%), cerebrovascular disease (20%), and anxiety (18%). ANA were present in all. The prevalence of anti-Rib-P was 26.6% in NPSLE and 16.6% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found in 56.7% in NPSLE and 43.4% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found to be highest in the patients of psychosis (66.6%) followed by central nerve system disease (63.63 %) and seizures (56.25%). There was an early onset of neuropsychiatric involvement. Anti-Rib-P antibodies as well as anti-neuronal antibodies did not show statistically significant correlation with neuropsychiatric manifestations in NPSLE patients.

Antinucleosome antibodies as a marker of active proliferative lupus nephritis.

PubMed

Bigler, Cornelia; Lopez-Trascasa, Margarita; Potlukova, Eliska; Moll, Solange; Danner, Doris; Schaller, Monica; Trendelenburg, Marten

2008-04-01

Antinucleosome autoantibodies were previously described to be a marker of active lupus nephritis. However, the true prevalence of antinucleosome antibodies at the time of active proliferative lupus nephritis has not been well established. Therefore, the aim of this study is to define the prevalence and diagnostic value of autoantibodies against nucleosomes as a marker for active proliferative lupus nephritis. Prospective multicenter diagnostic test study. 35 adult patients with systemic lupus erythematosus (SLE) at the time of the renal biopsy showing active class III or IV lupus nephritis compared with 59 control patients with SLE. Levels of antinucleosome antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Kidney biopsy findings of class III or IV lupus nephritis at the time of sampling in a study population versus clinically inactive or no nephritis in a control population. Increased concentrations of antinucleosome antibodies were found in 31 of 35 patients (89%) with active proliferative lupus nephritis compared with 47 of 59 control patients (80%) with SLE. No significant difference between the 2 groups with regard to number of positive patients (P = 0.2) or antibody concentrations (P = 0.2) could be found. The area under the receiver operating characteristic curve as a marker of the accuracy of the test in discriminating between proliferative lupus nephritis and inactive/no nephritis in patients with SLE was 0.581 (95% confidence interval, 0.47 to 0.70; P = 0.2). Increased concentrations of anti-dsDNA antibodies were found in 33 of 35 patients (94.3%) with active proliferative lupus nephritis compared with 49 of 58 control patients (84.5%) with SLE (P = 0.2). In patients with proliferative lupus nephritis, significantly higher titers of anti-dsDNA antibodies were detected compared with control patients with SLE (P < 0.001). The area under the receiver operating characteristic curve in discriminating between proliferative lupus nephritis and inactive/no nephritis in patients with SLE was 0.710 (95% confidence interval, 0.60 to 0.82; P < 0.001). Antinucleosome antibodies have a high prevalence in patients with severe lupus nephritis. However, our data suggest that determining antinucleosome antibodies is of limited help in the distinction of patients with active proliferative lupus nephritis from patients with SLE without active renal disease.

[Dyslipidaemia and atherogenic risk in patients with systemic lupus erythematosus].

PubMed

Batún Garrido, José Antonio de Jesús; Radillo Alba, Hugo Alberto; Hernández Núñez, Éufrates; Olán, Francisco

2016-07-15

Dyslipidaemia is a common comorbidity in patients with systemic lupus erythematosus. Fifty-one patients were included. Variables associated with the disease and the drugs used were recorded. Atherogenic risk was calculated. Chi square was used for categorical variables. ANOVA was performed and a logistic regression model to determine the association of the variables with the presence of dyslipidaemia. A percentage of 68.6 had dyslipidaemia. A significant difference between the presence of dyslipidaemia and activity index measured by SLEDAI was found, the presence of lupus nephritis, use of prednisone≥20mg/day, evolution of the disease<3 years. Significance between the absence of dyslipidaemia and use of hydroxychloroquine was found. SLEDAI≥4 and the use of prednisone≥20mg/day were independently associated with the presence of dyslipidaemia. The average of Castelli rate was 5.02, the Kannel index was 2.97 and triglyceride/HDL-C ratio was 5.24. Patients with systemic lupus erythematosus have a high prevalence of dyslipidaemia and a high atherogenic rate, which increases cardiovascular risk significantly. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Infections and systemic lupus erythematosus

PubMed Central

Skare, Thelma Larocca; Dagostini, Jéssica Scherer; Zanardi, Patricia Imai; Nisihara, Renato Mitsunori

2016-01-01

ABSTRACT Objective To determine the incidence of infections in a population of systemic lupus erythematosus individuals and the characteristics of infections regarding original site, as well as to study the possible associations between infections and treatment. Methods An analytical retrospective study using data from medical charts of systemic lupus erythematosus patients from a single university hospital. A total of 144 patients followed up for five years were included. Data collected comprised age of patients and age at onset of lupus, sex and ethnicity, disease duration before the study period, medications, cumulative dose of prednisone, occurrence of infections and their original site. Results The most frequent infections were urinary tract infections (correlated to use of prednisone − p<0.0001 and cyclophosphamide − p=0.045), upper airways infections (correlated to use of prednisone − p=0.0004, mycophenolate mofetil − p=0.0005, and cyclosporine − p=0.025), and pneumonia (associated to prednisone − p=0.017). Conclusion Prednisone was the drug more often associated with presence of infections, pointing to the need for a more judicious management of this drug. PMID:27074234

Why are kids with lupus at an increased risk of cardiovascular disease?

PubMed

Quinlan, Catherine; Marks, Stephen D; Tullus, Kjell

2016-06-01

Juvenile-onset systemic lupus erythematosus (SLE) is an aggressive multisystem autoimmune disease. Despite improvements in outcomes for adult patients, children with SLE continue to have a lower life expectancy than adults with SLE, with more aggressive disease, a higher incidence of lupus nephritis and there is an emerging awareness of their increased risk of cardiovascular disease (CVD). In this review, we discuss the evidence for an increased risk of CVD in SLE, its pathogenesis, and the clinical approach to its management.

Advanced and Conventional Magnetic Resonance Imaging in Neuropsychiatric Lupus

PubMed Central

Sarbu, Nicolae; Bargalló, Núria; Cervera, Ricard

2015-01-01

Neuropsychiatric lupus is a major diagnostic challenge, and a main cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Magnetic resonance imaging (MRI) is, by far, the main tool for assessing the brain in this disease. Conventional and advanced MRI techniques are used to help establishing the diagnosis, to rule out alternative diagnoses, and recently, to monitor the evolution of the disease. This review explores the neuroimaging findings in SLE, including the recent advances in new MRI methods. PMID:26236469

Accelerated recovery from nephrotic syndrome with acute renal failure by double filtration plasmapheresis in a patient with lupus podocytopathy.

PubMed

Iwazu, Yoshitaka; Akimoto, Tetsu; Izawa, Sayoko; Inoue, Makoto; Muto, Shigeaki; Ando, Yasuhiro; Iwazu, Kana; Fukushima, Noriyoshi; Yumura, Wako; Kusano, Eiji

2012-06-01

We describe a case of an adult female who presented with nephrotic syndrome. She was diagnosed with systemic lupus erythematosus with serum antinuclear antibodies, leucopenia with lymphopenia, butterfly erythema, and nephrotic syndrome. Renal biopsy revealed normal glomeruli with diffuse effacement of the foot processes, consistent with lupus podocytopathy. Although human albumin replacement was performed initially, acute renal failure developed rapidly. Therefore, she was treated with double filtration plasmapheresis (DFPP) in addition to oral steroid. After steroid therapy combined with DFPP, the renal function and proteinuria improved rapidly. Although the impact of DFPP on the treatment of lupus nephritis remains to be delineated, our observations suggest that DFPP in lupus podocytopathy played a pivotal role in facilitating the early recovery from renal injuries. Because of the rapid improvement of renal function without any change in body weight by DFPP, acute renal failure in the setting of lupus podocytopathy might contribute to an alternative pathophysiological factor for the diminished glomerular filtration rate, similar to that observed in the setting of idiopathic minimal change glomerulopathy.

[Cardiovascular manifestations in systemic lupus erythematosus in Dakar: Descriptive study about 50 cases].

PubMed

Ngaïdé, A A; Ly, F; Ly, K; Diao, M; Kane, Ad; Mbaye, A; Lèye, M; Aw, F; Sarr, S A; Dioum, M; Ndao, C T; Gaye, N D; Ndiaye, M B; Bodian, M; Bah, M B; Ndiaye, M; Cissé, A F; Kouamé, I; Tabane, A; Mingou, J S; Thiombiano, P; Kane, A; Bâ, S A

2016-12-01

Systemic lupus erythematosus is a non-specific inflammatory disorder of an organ of unknown cause and autoimmune origin. Visceral injuries, including those cardiovascular, determine the prognosis of this disease primarily affecting women. The objectives of this study were to determine the frequency and describe the cardiovascular manifestations in systemic lupus erythematosus in a lupus population of the Dakar region. This is a multicenter prospective study descriptive and analytical conducted in the region of Dakar (Senegal) from 14 February 2011 to 2 July 2012. Patients were either hospitalized or monitored as outpatients. Included were all patients with lupus and meeting at least four criteria of the American College of Rheumatology of lupus disease classification 1997. All patients underwent physical examination, an electrocardiogram and an echocardiogram looking for cardiovascular damage. The collected data were entered into the Epi Info version 3.5.1 and processed with SPSS 16.0 software. Quantitative variables are described in the median and the qualitative workforce, percentage and frequency. We have included 50 patients. The average age of the population was 36.18 years. A female predominance is noted with a sex ratio man/woman of 0.09. Cardiovascular functional symptoms were dominated by dyspnea stage II to IV NYHA (26%) and palpitations (22%). The physical signs we have found were mainly tachycardia (40%), spontaneous turgor of the jugular veins (29%), a muffling of the heart sounds (29%) and a infandibulopulmonairy shock (18%). The frequency of cardiovascular events was 46%. Electrical cardiac events were dominated by sinus tachycardia (40%) of repolarization disorders (16.3%) type of ischemia, injury, ischemia injury, necrosis and hypertrophy with 18% atrial and left ventricular hypertrophy each. Furthermore, one case of BAV first degree at 280 ms was recorded. We found 19 cases of pericarditis including 2 tamponade, 3 cases of dilated cardiomyopathy hyperkinesias with impaired ejection fraction less than 35% and 8 patients with mild PAH important. In systemic lupus erythematosus, cardiovascular events are worrying and may remain asymptomatic for awhile. Their research must be systematic in order to treat early.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

PubMed

Lewandowski, L B; Schanberg, L E; Thielman, N; Phuti, A; Kalla, A A; Okpechi, I; Nourse, P; Gajjar, P; Faller, G; Ambaram, P; Reuter, H; Spittal, G; Scott, C

2017-02-01

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

Mycobacterium intracellulare infection of the shoulder and spine in a patient with steroid-treated systemic Lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zvetina, J.R.; Rubinstein, H.; Demos, T.C.

1982-05-01

Atypical mycobacterial infections of bone are rare. A patient with systemic lupus erythematosus treated with steroids developed an M. intracellulare infection of the shoulder and spine. These infections are insidious and diagnosis is difficult. Marked involvement of one joint, large effusion, or aspirated small synovial fragments suggest an atypical tuberculous joint infection.

Infection in systemic lupus erythematosus, similarities, and differences with lupus flare

PubMed Central

Jung, Ju-Yang; Suh, Chang-Hee

2017-01-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, and its pathogenesis is unclear and complicated. Infection and SLE are similar in that they both cause inf lammatory reactions in the immune system; however, one functions to protect the body, whereas the other is activated to damage the body. Infection is known as one of the common trigger factors for SLE; there are a number of reports on infectious agents that provoke autoimmune response. Several viruses, bacteria, and protozoa were revealed to cause immune dysfunction by molecular mimicry, epitope spreading, and bystander activation. In contrast, certain pathogens were revealed to protect from immune dysregulation. Infection can be threatening to patients with SLE who have a compromised immune system, and it is regarded as one of the common causes of mortality in SLE. A clinical distinction between infection and lupus f lare up is required when patients with SLE present fevers. With a close-up assessment of symptoms and physical examination, C-reactive protein and disease activity markers play a major role in differentiating the different disease conditions. Vaccination is necessary because protection against infection is important in patients with SLE. PMID:28490724

New-onset systemic lupus erythematosus in a long-term hemodialysis patient with acute pleuritis and pneumonitis.

PubMed

Hiyamuta, Hiroto; Yamada, Shunsuke; Yotsueda, Ryusuke; Hasegawa, Shoko; Nakano, Toshiaki; Taniguchi, Masatomo; Tsukamoto, Hiroshi; Kitazono, Takanari; Tsuruya, Kazuhiko

2015-11-01

A 61-year-old woman, with a 25-year history of maintenance hemodialysis due to end-stage renal disease of unknown causes, was admitted because of systemic joint pain and inflammatory response of unknown etiology that persisted for 1 month. Laboratory data on admission revealed leukocytopenia, lymphocytopenia, high serum C-reactive protein, and positivity for antinuclear antibody (ANA) and anti-double strand DNA. After admission, she progressively developed cough and dyspnea. A chest radiograph revealed bilateral ground glass opacity and pleural effusion. A thoracentesis revealed lupus erythematosus cells, suggesting lupus pleuritis. A chest computed tomography showed a pattern of diffuse alveolar damage compatible with acute lupus pneumonitis. She fulfilled the American Rheumatism Association diagnostic criteria for systemic lupus erythematosus (SLE). Methylprednisolone pulse therapy followed by oral prednisone treatment improved the clinical symptoms and laboratory abnormalities. ANA was negative 25 years earlier when she first started hemodialysis and she had neither clinical nor serological abnormalities related to SLE during the last 25 years. Further, she had neither received drugs that can cause drug-induced SLE, nor had a history of ultraviolet ray exposure, pregnancy, blood transfusion, trauma and smoking. This report suggests that new-onset SLE can develop in patients undergoing long-term dialysis. Hence, when we encounter dialysis patients with arthralgia and/or respiratory disorders, we should consider the possibility of new-onset SLE.

Gut Microbiota in Human Systemic Lupus Erythematosus and a Mouse Model of Lupus.

PubMed

Luo, Xin M; Edwards, Michael R; Mu, Qinghui; Yu, Yang; Vieson, Miranda D; Reilly, Christopher M; Ahmed, S Ansar; Bankole, Adegbenga A

2018-02-15

Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of the gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis in a small group of SLE patients with active disease. The composition of the gut microbiota changed markedly before and after the onset of lupus disease in NZB/W F1 mice, with greater diversity and increased representation of several bacterial species as lupus progressed from the predisease stage to the diseased stage. However, we did not control for age and the cage effect. Using dexamethasone as an intervention to treat SLE-like signs, we also found that a greater abundance of a group of lactobacilli (for which a species assignment could not be made) in the gut microbiota might be correlated with more severe disease in NZB/W F1 mice. Results of the human study suggest that, compared to control subjects without immune-mediated diseases, SLE patients with active lupus disease possessed an altered gut microbiota that differed in several particular bacterial species (within the genera Odoribacter and Blautia and an unnamed genus in the family Rikenellaceae ) and was less diverse, with increased representation of Gram-negative bacteria. The Firmicutes / Bacteroidetes ratios did not differ between the SLE microbiota and the non-SLE microbiota in our human cohort. IMPORTANCE SLE is a complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota has been reported for both mice and humans with SLE. In this emerging field, however, more studies are required to delineate the roles of the gut microbiota in different lupus-prone mouse models and people with diverse manifestations of SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice and a group of SLE patients with active disease. Copyright © 2018 American Society for Microbiology.

High-Throughput Sequencing Reveals Circulating miRNAs as Potential Biomarkers of Kidney Damage in Patients with Systemic Lupus Erythematosus.

PubMed

Navarro-Quiroz, Elkin; Pacheco-Lugo, Lisandro; Lorenzi, Hernan; Díaz-Olmos, Yirys; Almendrales, Lisneth; Rico, Edwin; Navarro, Roberto; España-Puccini, Pierine; Iglesias, Antonio; Egea, Eduardo; Aroca, Gustavo

2016-01-01

Renal involvement is one of the most severe manifestations of systemic lupus erythematosus (SLE). Renal biopsy is the gold standard when it comes to knowing whether a patient has lupus nephritis, and the degree of renal disease present. However, the biopsy has various complications, bleeding being the most common. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with SLE is a priority. Micro RNAs (miRNAs) are differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. The aim of this study was to identify changes in the abundance of miRNAs in plasma samples from patients with lupus nephritis that could potentially allow the diagnosis of renal damage in SLE patients. This is an observational case-control cross-sectional study, in which we characterized the differential abundance profiles of miRNAs among patients with different degrees of lupus compared with SLE patients without renal involvement and healthy control individuals. We found 89 miRNAs with changes in their abundance between lupus nephritis patients and healthy controls, and 17 miRNAs that showed significant variations between SLE patients with or without renal involvement. Validation for qPCR of a group of miRNAs on additional samples from lupus patients with or without nephritis, and from healthy individuals, showed that five miRNAs presented an average detection sensitivity of 97%, a specificity of 70.3%, a positive predictive value of 82.5%, a negative predictive value of 96% and a diagnosis efficiency of 87.9%. These results strongly suggest that miR-221-5p, miR-380-3p, miR-556-5p, miR-758-3p and miR-3074-3p are potential diagnostic biomarkers of lupus nephritis in patients with SLE. The observed differential pattern of miRNA abundance may have functional implications in the pathophysiology of SLE renal damage.

Proliferative lupus nephritis in the absence of overt systemic lupus erythematosus: A historical study of 12 adult patients.

PubMed

Touzot, Maxime; Terrier, Cécile Saint-Pastou; Faguer, Stanislas; Masson, Ingrid; François, Hélène; Couzi, Lionel; Hummel, Aurélie; Quellard, Nathalie; Touchard, Guy; Jourde-Chiche, Noémie; Goujon, Jean-Michel; Daugas, Eric

2017-12-01

Severe lupus nephritis in the absence of systemic lupus erythematosus (SLE) is a rare condition with an unclear clinical presentation and outcome.We conducted a historical observational study of 12 adult (age >18 years) patients with biopsy-proven severe lupus nephritis or lupus-like nephritis without SLE immunological markers at diagnosis or during follow-up. Excluded were patients with chronic infections with HIV or hepatitis B or C; patients with a bacterial infectious disease; and patients with pure membranous nephropathy. Electron microscopy was retrospectively performed when the material was available. End points were the proportion of patients with a complete response (urine protein to creatinine ratio <0.5 g/day and a normal or near-normal eGFR), partial response (≥50% reduction in proteinuria to subnephrotic levels and a normal or near-normal eGFR), or nonresponse at 12 months or later after the initiation of the treatment.The study included 12 patients (66% female) with a median age of 36.5 years. At diagnosis, median creatinine and proteinuria levels were 1.21 mg/dL (range 0.5-11.6) and 7.5 g/day (1.4-26.7), respectively. Six patients had nephrotic syndrome and acute kidney injury. Renal biopsy examinations revealed class III or class IV A/C lupus nephritis in all cases. Electron microscopy was performed on samples from 5 patients. The results showed mesangial and subendothelial dense deposits consistent with LN in 4 cases, and a retrospective diagnosis of pseudo-amyloid fibrillary glomerulonephritis was made in 1 patient.Patients received immunosuppressive therapy consisting of induction therapy followed by maintenance therapy, similar to treatment for severe lupus nephritis. Remission was recorded in 10 patients at 12 months after the initiation of treatment. One patient reached end-stage renal disease. After a median follow-up of 24 months, 2 patients relapsed.Lupus nephritis in the absence of overt SLE is a nosological entity requiring careful etiological investigation, including systematic electron microscopy examination of renal biopsies to rule out fibrillary glomerulonephritis. In this series, most patients presented with severe glomerulonephritis, which was highly similar to lupus nephritis at presentation and in terms of response to immunosuppressive therapy.

A multi-group confirmatory factor analyses of the LupusPRO between southern California and Filipino samples of patients with systemic lupus erythematosus.

PubMed

Azizoddin, D R; Olmstead, R; Cost, C; Jolly, M; Ayeroff, J; Racaza, G; Sumner, L A; Ormseth, S; Weisman, M; Nicassio, P M

2017-08-01

Introduction Systemic lupus erythematosus (SLE) leads to a range of biopsychosocial health outcomes through an unpredictable and complex disease path. The LupusPRO is a comprehensive, self-report measure developed specifically for populations with SLE, which assesses both health-related quality of life and non-health related quality of life. Given its increasingly widespread use, additional research is needed to evaluate the psychometric integrity of the LupusPRO across diverse populations. The objectives of this study were to evaluate the performance of the LupusPRO in two divergent patient samples and the model fit between both samples. Methods Two diverse samples with SLE included 136 patients from an ethnically-diverse, urban region in southern California and 100 from an ethnically-homogenous, rural region in Manila, Philippines. All patients met the ACR classification criteria for SLE. Confirmatory factor analysis (CFAs) were conducted in each sample separately and combined to provide evidence of the factorial integrity of the 12 subscales in the LupusPRO. Results Demographic analyses indicated significant differences in age, disease activity and duration, education, income, insurance, and medication use between groups. Results of the separate CFAs indicated moderate fit to the data for the hypothesized 12-factor model for both the Manila and southern California groups, respectively [χ 2 (794) = 1283.32, p < 0.001, Comparative Fit Index (CFI) = 0.793; χ 2 (794) =1398.44, p < 0.001, CFI = 0.858]. When the factor structures of the LupusPRO in the southern California and Manila groups were constrained to be equal between the two groups, findings revealed that the factor structures of measured variables fit the two groups reasonably well [χ 2  (1697) = 2950.413, df = 1697, p < 0.000; CFI = 0.811]. After removing seven constraints and eight correlations suggested by the Lagrange multiplier test, the model fit improved significantly [χ 2 (15) = 147.165, p < 0.000]. Conclusions This research provides significant support for the subscale structure of the LupusPRO in two disparate cultural samples of SLE patients. Despite significant sociodemographic and clinical differences between the two samples, for the most part, the LupusPRO performed similarly in both samples.

Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus nephritis from 2000 to 2004 among children in the US Medicaid beneficiary population.

PubMed

Hiraki, Linda T; Feldman, Candace H; Liu, Jun; Alarcón, Graciela S; Fischer, Michael A; Winkelmayer, Wolfgang C; Costenbader, Karen H

2012-08-01

To investigate the nationwide prevalence, incidence, and sociodemographics of systemic lupus erythematosus (SLE) and lupus nephritis among children in the US Medicaid beneficiary population. Children ages 3 years to <18 years with a diagnosis of SLE (defined as ≥3 claims with an International Classification of Diseases, Ninth Revision [ICD-9] code of 710.0 for SLE, each >30 days apart) were identified from the US Medicaid Analytic eXtract database from 2000 to 2004. This database contains all inpatient and outpatient Medicaid claims for 47 US states and the District of Columbia. Lupus nephritis was identified from ≥2 ICD-9 billing codes for glomerulonephritis, proteinuria, or renal failure, each recorded >30 days apart. The prevalence and incidence of SLE and lupus nephritis were calculated among Medicaid-enrolled children overall and within sociodemographic groups. Of the 30,420,597 Medicaid-enrolled children during these years, 2,959 were identified as having SLE. The prevalence of SLE was 9.73 (95% confidence interval [95% CI] 9.38-10.08) per 100,000 Medicaid-enrolled children. Among the children with SLE, 84% were female, 40% were African American, 25% were Hispanic, 21% were White, and 42% resided in the South region of the US. Moreover, of the children with SLE, 1,106 (37%) had lupus nephritis, representing a prevalence of 3.64 (95% CI 3.43-3.86) per 100,000 children. The average annual incidence of SLE was 2.22 cases (95% CI 2.05-2.40) and that of lupus nephritis was 0.72 cases (95% CI 0.63-0.83) per 100,000 Medicaid enrollees per year. The prevalence and incidence rates of SLE and lupus nephritis increased with age, were higher in girls than in boys, and were higher in all non-White racial/ethnic groups. In the current study, the prevalence and incidence rates of SLE among Medicaid-enrolled children in the US are high compared to studies in other populations. In addition, these data represent the first population-based estimates of the prevalence and incidence of lupus nephritis in the US to date. Copyright © 2012 by the American College of Rheumatology.

Serum neuron specific enolase - a novel indicator for neuropsychiatric systemic lupus erythematosus?

PubMed

Hawro, T; Bogucki, A; Krupińska-Kun, M; Maurer, M; Woźniacka, A

2015-12-01

Neuropsychiatric (NP) lupus, a common manifestation of systemic lupus erythematosus (SLE), is still insufficiently understood, in part, because of the lack of specific biomarkers. Neuron specific enolase (NSE), an important neuronal glycolytic enzyme, shows increased serum levels following acute brain injury, and decreased serum levels in several chronic disorders of the nervous system, including multi infarct dementia, multiple sclerosis and depression. The aim of the study was to evaluate serum NSE levels in SLE patients with and without nervous system involvement, and in healthy controls, and to assess the correlation of NSE serum levels of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) with clinical parameters. The study comprised 47 SLE patients and 28 controls. SLE activity was assessed using the Systemic Lupus Activity Measure (SLAM). A neurologist and a psychiatrist examined all patients. NP involvement was diagnosed according to strict NPSLE criteria proposed by Ainiala and coworkers, as modification to American College of Rheumatology (ACR) nomenclature and case definitions. NSE serum levels were determined by use of an immunoassay. Mean NSE serum concentrations in patients with NPSLE were significantly lower than in non-NPSLE patients (6.3 ± 2.6 µg/L vs. 9.7 ± 3.3 µg/L, p < 0.01) and in controls (8.8 ± 3.3 µg/L, p < 0.05). There were significant negative correlations between NSE serum levels and SLE activity (r = -0.42, p < 0.05) and the number of NPSLE manifestations diagnosed (-0.37; p = 0.001). Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE. © The Author(s) 2015.

Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study

PubMed Central

Clark, William F.; Lindsay, Robert M.; Cattran, Daniel C.; Chodirker, William B.; Barnes, Colin C.; Linton, Adam L.

1981-01-01

Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis. PMID:7272867

Epidemiology of systemic lupus erythematosus and cutaneous lupus erythematosus in a predominantly white population in the United States.

PubMed

Jarukitsopa, Sudumpai; Hoganson, Deana D; Crowson, Cynthia S; Sokumbi, Olayemi; Davis, Mark D; Michet, Clement J; Matteson, Eric L; Maradit Kremers, Hilal; Chowdhary, Vaidehi R

2015-05-01

Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993-2005. SLE cases were identified from review of medical records and fulfilled the 1982 American College of Rheumatology classification criteria. CLE cases included patients with classic discoid lupus erythematosus, subacute CLE, lupus panniculitis, and bullous lupus erythematosus. Age- and sex-adjusted incidence and prevalence were standardized to the 2000 US white population. The age- and sex-adjusted incidence of SLE (2.9 per 100,000; 95% confidence interval [95% CI] 2.0-3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1-5.2, P = 0.10). However, the incidence of CLE was 3 times higher than SLE in men (2.4 versus 0.8 per 100,000; P = 0.009). The age- and sex-adjusted prevalence of CLE on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; P < 0.001). The prevalences of CLE and SLE in women were similar, but the prevalence of CLE was higher in men than in women (56.9 versus 1.6 per 100,000; P < 0.001). The incidence of CLE rose steadily with age and peaked at 60-69 years. The incidences of CLE and SLE are similar, but CLE is more common than SLE in men and in older adults. These findings may reflect differences in genetic or environmental etiology of CLE. © 2015, American College of Rheumatology.

Systemic lupus erythematosus: Is it one disease?

PubMed

Rivas-Larrauri, Francisco; Yamazaki-Nakashimada, Marco Antonio

2016-01-01

Systemic lupus erythematosus (SLE) is a multisystemic disease with a variety of clinical presentations. Monogenic predisposing conditions to the development of this disease have been described. As examples, an impaired expression of interferon-α regulated genes or complement deficiencies have been reported in patients with SLE, with particular clinical presentations. Those defects present particular presentations and a different severity, making an argument that lupus is not a single disease but many. Treatment could be individualized depending on the underlying defect generating the subtype of the disease. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Urtica dioica agglutinin, a V beta 8.3-specific superantigen, prevents the development of the systemic lupus erythematosus-like pathology of MRL lpr/lpr mice.

PubMed

Musette, P; Galelli, A; Chabre, H; Callard, P; Peumans, W; Truffa-Bachi, P; Kourilsky, P; Gachelin, G

1996-08-01

The V beta 8.3-specific superantigenic lectin Urtica dioica agglutinin (UDA) was used to delete the V beta 8.3+ T cells in MRL lpr/lpr mice. In contrast to the systemic lupus erythematosus-like pathology which progresses with age in the phosphate-buffered saline-injected MRL lpr/lpr controls, UDA-treated animals did not develop overt clinical signs of lupus and nephritis. The pathogenic T cell clones thus reside within the V beta 8.3+ T cell population, which includes an expanded T cell clone described previously. Finally, UDA alters the production of autoantibodies in a sex-dependent manner.

Lupus erythematosus cell preparation, antinuclear factor and antideoxyribonucleic acid antibody incongruity in systemic lupus erythematosus.

PubMed

Chee, Y C

1983-01-01

'Total antinuclear antibody' (ANF) is detected by the fluorescent antinuclear antibody technique which is a screening test, positive in 99% of systemic lupus erythematosus (SLE) sera. The LE factor (positive in 75% of SLE sera), like the anti-DNA antibody, is an antinuclear antibody but directed against DNA-histone. ANF-negative SLE is a clinical entity with absence of these antibodies. A false negative ANF, in the presence of high titre anti-DNA antibody and/or LE cells, is illustrated in two cases of SLE. Postulated mechanisms for this phenomenon are interference in ANF detection by rheumatoid factor, and the prozone effect on the immunofluorescent tests.

Serological levels of apoptotic bodies, sFAS and TNF in lupus erythematosus.

PubMed

Alecu, M; Coman, G; Alecu, S

In our study we have investigated the presence of apoptotic bodies, soluble FAS receptor and TNF (tumor necrosis factor) in three clinical forms of lupus erythematosus. Determinations were performed in attack period of: systemic lupus erythematosus (SLE) for 20 patients, 20 patients with subacute cutaneous lupus erythematosus (SCLE), 20 patients with chronic discoid lupus erythematosus (DLE). Determinations were performed by ELISA (for apoptotic bodies, kit Boehringer, normal values 400-800 mU), (for sFAS, kit R&D Systems, normal values 4500-17000 pg/ml) (for TNF, ELISA kit R&D Systems, normal values 0.4-3.6 pg/ml). Results in SLE: apoptotic bodies were increased in 16 cases (980-1030); sFAS in 18 cases (17000-24000 pg/ml) TNF was increased in all 20 cases (40-140 pg/ml). In SCLE with multiple cutaneous lesions and without internal organs disturbance the apoptotic bodies were increased in 10 cases (960-1030 pg/ml), sFAS in 9 cases (17000-22000 pg/ml), and TNF alpha in 9 cases. In DLE, apoptotic bodies were increased in 2 patients (980-1010 pg/ml), sFAS in 3 patients (17000-20000 pg/ml) and TNF in 2 patients (20-40 pg/mil). Investigated values were slightly correlated with immune parameters (anti dsDNA antibodies), but they were correlated with the presence of renal disturbances or extension of cutaneous lesions. We consider that the presence of increased apoptotic bodies as a result of peripheral mononuclear cells apoptosis appear as a nauto-limiting mechanism in a pathological immune response. The increase of sFAS in lupus patients serum might be interpreted as an alteration of apoptosis respectively a deficit in apoptosis which has as a first consequence the persistence of B and T lymphocytes, activated, in the pathogen immune response.

Influence of Education on Disease Activity and Damage in Systemic Lupus Erythematosus: Data From the 1000 Canadian Faces of Lupus.

PubMed

George, Angela; Wong-Pak, Andrew; Peschken, Christine A; Silverman, Earl; Pineau, Christian; Smith, C Douglas; Arbillaga, Hector; Zummer, Michel; Bernatsky, Sasha; Hudson, Marie; Hitchon, Carol; Fortin, Paul R; Nevskaya, Tatiana; Pope, Janet E

2017-01-01

To determine whether socioeconomic status assessed by education is associated with disease activity and the risk of organ damage in systemic lupus erythematosus (SLE). Data from the 1000 Canadian Faces of Lupus, a multicenter database of adult SLE patients, was used to compare education as either low (did not complete high school) or high (completed high school or further) for disease activity and damage. Education was also studied as a continuous variable. The relationships between education and SLE outcomes (any organ damage defined as a Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI] score ≥1, serious organ damage [SDI score ≥3], and end-stage renal disease) were evaluated using logistic regression analyses adjusted for age, sex, race/ethnicity, and disease duration. A total of 562 SLE patients met inclusion criteria (mean age 47 years, 91% female, and mean disease duration of 10 years); 81% had high education. The low education group was twice as likely to be work disabled (30%; P < 0.0001); they had higher disease activity and reduced renal function. Linear regression analysis revealed that low education was significantly associated with higher disease activity at enrollment into the 1000 Canadian Faces of Lupus database, after adjustment for age (at entry and at diagnosis), race/ethnicity, and sex (B 1.255 + 0.507 [SE], β = 0.115, P = 0.014). In our adjusted logistic regression models we were unable to demonstrate significant associations between education and SLE damage. Results did not change when varying the education variable. In this cohort, low education was associated cross-sectionally with higher disease activity and work disability, but not damage. © 2016, American College of Rheumatology.

Predictive risk factors for failure to induction therapy of lupus nephritis in a cohort of Colombian patients.

PubMed

Pinto Peñaranda, Luis Fernando; Castro Mercado, Inis Lizeth; Duque Caballero, Vladimir; Márquez Hernández, Javier Darío; Velásquez Franco, Carlos Jaime

2014-01-01

To determine the predictors of failure to obtain remission after induction therapy for proliferative lupus nephritis in a group of northwestern Colombian patients. A retrospective study was conducted. We included patients with systemic lupus erythematosus according to the American College of Rheumatology criteria who had nephritis confirmed by renal biopsy. We followed 84 patients: 88.1% female, and 11.9% male. The mean age at diagnosis of systemic lupus erythematosus was 27.5±11.8 years (9-70). The average time between diagnosis of systemic lupus erythematosus and proliferative nephritis onset was 13.6 months (0-168). Histopathologic type: iv (78.57%), iii (15.47%), iii-iv/v (5.96%). Activity index: 6.7±4.6. Chronicity index: 2±2.7. 24-hour proteinuria (mg): 6,164 (130-18,100). Baseline creatinine: 1.14 mg/dL (0.43-7.4). Induction therapy: Steroids (100%), cyclophosphamide (76.2%) and mycophenolate mofetil (23.8%). At six months, 56% of individuals failed to achieve partial or complete remission. Predictors of failure to induction therapy were, in accordance with the bivariate analysis (OR; 95%CI): creatinine level more than 1.2mg/dL (10.8; 3.18-36.84; P<.005), nephrotic range proteinuria (11.9; 3.09-45.8; P<.001), and an activity index above 8 (5.04; 1.7-14.3; P<.001). In the multivariate analysis, only baseline creatinine higher than 1.2mg/dL (10.92; 2.65-45.02; P=.001), and nephrotic range proteinuria (9.81; 1.85-52.04; P=.007) were significant. A significant percentage of Colombian patients fail to achieve remission of proliferative lupus nephritis after six months of treatment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Dynamics of mononuclear phagocyte system Fc receptor function in systemic lupus erythematosus. Relation to disease activity and circulating immune complexes.

PubMed Central

Kimberly, R P; Parris, T M; Inman, R D; McDougal, J S

1983-01-01

Seventeen pairs of longitudinal studies of mononuclear phagocyte system (MPS) Fc receptor function in 15 patients with systemic lupus were performed to explore the dynamic range of Fc receptor dysfunction in lupus and to establish the relationships between MPS function, clinical disease activity and circulating immune complexes (CIC). Fc receptor function was measured by the clearance of IgG sensitized autologous erythrocytes. At the time of first study the degree of MPS dysfunction was correlated with both clinical activity (P less than 0.05) and CIC (P less than 0.05). At follow-up patients with a change in clinical status show significantly larger changes in clearance function compared to clinically stable patients (206 min vs 7 min; P less than 0.001). MPS function changed concordantly with a change in clinical status in all cases (P = 0.002). Longitudinal assessments did not demonstrate concordance of changes in MPS function and CIC, measured by three different assays. The MPS Fc receptor defect in systemic lupus is dynamic and closely associated with disease activity. The lack of concordance of the defect with changes in CIC suggests that either CIC does not adequately reflect receptor site saturation or that other factors may also contribute to the magnitude of MPS dysfunction. PMID:6839542

Pathogenic mechanisms in systemic lupus erythematosus.

PubMed

Perl, Andras

2010-02-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by the dysfunction of T cells, B cells, and dendritic cells and by the production of antinuclear autoantibodies. This editorial provides a synopsis of newly discovered genetic factors and signaling pathways in lupus pathogenesis that are documented in 11 state-of-the-art reviews and original articles. Mitochondrial hyperpolarization underlies mitochondrial dysfunction, depletion of ATP, oxidative stress, abnormal activation, and death signal processing in lupus T cells. The mammalian target of rapamycin, which is a sensor of the mitochondrial transmembrane potential, has been successfully targeted for treatment of SLE with rapamycin or sirolimus in both patients and animal models. Inhibition of oxidative stress, nitric oxide production, expression of endogenous retroviral and repetitive elements such as HRES-1, the long interspersed nuclear elements 1, Trex1, interferon alpha (IFN-alpha), toll-like receptors 7 and 9 (TLR-7/9), high-mobility group B1 protein, extracellular signal-regulated kinase, DNA methyl transferase 1, histone deacetylase, spleen tyrosine kinase, proteasome function, lysosome function, endosome recycling, actin cytoskeleton formation, the nuclear factor kappa B pathway, and activation of cytotoxic T cells showed efficacy in animal models of lupus. Although B cell depletion and blockade of anti-DNA antibodies and T-B cell interaction have shown success in animal models, human studies are currently ongoing to establish the value of several target molecules for treatment of patients with lupus. Ongoing oxidative stress and inflammation lead to accelerated atherosclerosis that emerged as a significant cause of mortality in SLE.

The French-Canadian validation of a disease-specific, patient-reported outcome measure for lupus.

PubMed

Bourré-Tessier, J; Clarke, A E; Kosinski, M; Mikolaitis-Preuss, R A; Bernatsky, S; Block, J A; Jolly, M

2014-12-01

The objective of this paper is to perform the cross-cultural validation of the French version of the LupusPRO, a disease-targeted patient-reported outcome measure, among systemic lupus erythematosus (SLE) patients in Canada. The French version of the LupusPRO and the MOS SF-36 were administered; demographic, clinical and serological characteristics were obtained. Disease activity (SELENA-SLEDAI and the Lupus Foundation of America definition of flare) and damage (SLICC/ACR SDI) were assessed. Physician disease activity and damage assessments were ascertained using visual analog scales. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity, damage or health status) and known group validity were tested. A total of 99 French-Canadian SLE patients participated (97% women, mean (SD) age 45.2 (14.5) years). The median (IQR) SELENA-SLEDAI and SDI were 3.5 (6.0) and 1.0 (2.0), respectively. The ICR of the LupusPRO domains ranged from 0.81 to 0.93 (except for lupus symptoms, procreation and coping), while TRT ranged from 0.72 to 0.95. Convergent and discriminant validity, criterion validity and known group validity against disease activity, damage and health status measures were observed. Confirmatory factor analysis showed a good fit. The LupusPRO has fair psychometric properties among French-Canadian patients with SLE. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Modulating proximal cell signaling by targeting Btk ameliorates humoral autoimmunity and end-organ disease in murine lupus

PubMed Central

2012-01-01

Introduction Systemic lupus erythematosus is a chronic autoimmune disease characterized by an abundance of autoantibodies against nuclear antigens. Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity. The aim of this study was to determine the effect of Btk inhibition by PCI-32765 on the development of lupus in lupus-prone B6.Sle1 and B6.Sle1.Sle3 mice. Methods B6.Sle1 or B6.Sle1.Sle3 mice received drinking water containing either the Btk inhibitor PCI-32765 or vehicle for 56 days. Following treatment, mice were examined for clinical and pathological characteristics of lupus. The effect of PCI-32765 on specific cell types was also investigated. Results In this study, we report that Btk inhibition dampens humoral autoimmunity in B6.Sle1 monocongenic mice. Moreover, in B6.Sle1.Sle3 bicongenic mice that are prone to severe lupus, Btk inhibition also dampens humoral and cellular autoimmunity, as well as lupus nephritis. Conclusions These findings suggest that partial crippling of cell signaling in B cells and antigen presenting cells (APCs) may be a viable alternative to total depletion of these cells as a therapeutic modality for lupus. PMID:23136880

Quality-of-life measurements in multiethnic patients with systemic lupus erythematosus: cross-cultural issues.

PubMed

Toloza, Sergio M A; Jolly, Meenakshi; Alarcón, Graciela S

2010-08-01

Although the survival rate for systemic lupus erythematosus (SLE) has improved dramatically during the past 50 years, the quality of life of patients afflicted with this disease remains poor. Currently existent measures of disease activity and damage in SLE do not capture the patient's perspective and health-related quality of life (HRQoL). Most studies in SLE pertaining to HRQoL are from developed Western societies, with only a few from others. These studies have been conducted predominantly in women and using the Medical Outcomes Survey Short Form 36, a generic HRQoL instrument that has been shown not to be sensitive to change in lupus. Existent lupus-specific HRQoL measures have not yet been used in SLE clinical trials. New HRQoL research tools are currently undergoing validation in different countries, languages, and cultural settings, which may help dissect the underlying role of socioeconomic status and specific disease-related features that impact SLE-related quality of life.

Intentional overdose of azathioprine in a patient with systemic lupus erythematosus.

PubMed

Mahmood, K; Khan, A M; Ramanan, A V; Martin, K

2013-11-01

A 14-year-old girl with systemic lupus erythematosus presented with a mixed overdose of paracetamol, ibuprofen and azathioprine (1500 mg) following a deliberate self-harm attempt. The patient was admitted and monitored. No adverse effects were observed. A review of the literature showed very few reported azathioprine overdoses. Lupus patients are at risk of developing low mood and depression (and related self-harm including overdose of medication). This can be as a consequence of the disease process itself or in reaction to the stresses of living with a chronic disease, which are perhaps particularly acute in some adolescents with the disease. An intentional overdose in a patient with lupus is clearly a cry for help and should be appropriately managed. Counselling of young people and their parents about possible mood disorders is an important part of the management of this chronic disease. Despite the theoretical risk of significant myelosuppression as well as other potential adverse effects, azathioprine in acute overdose seems to be generally well tolerated.

Laboratory testing for the diagnosis, evaluation, and management of systemic lupus erythematosus: Still more questions for the next generations: A Tribute and Thanks and in Memory of my mentor: Henry G. Kunkel.

PubMed

Schur, Peter H

2016-11-01

This paper is a review, personal memoir, a tribute to Henry Kunkel, and a critique regarding laboratory tests used for the evaluation, diagnosis, and understanding Autoimmune Rheumatic Diseases, in particular systemic lupus erythematosus (SLE). Copyright © 2016 Elsevier Inc. All rights reserved.

Primary Psychiatric Disorder Masking the Diagnosis of Neuropsychiatric Lupus in a Patient with Altered Mental Status: A Case Report.

PubMed

Perez, Osman; Dave, Kairavee; Almanzar, Aimee; Prodhan, Tajul; Concepion, Livasky

2017-10-23

Neuropsychiatric systemic lupus erythematosus (NPSLE) has a wide variety of neurologic and psychiatric features. NPSLE symptoms and the psychotic features of primary psychiatric disorders often overlap with each other. These psychotic features often mask and delay the diagnosis of NPSLE. We present the case of a 59-year-old female previously diagnosed with bipolar disorder and generalized anxiety disorder presenting with altered mental status (AMS), subsequently diagnosed with neuropsychiatric lupus. Initially, medication overdose was suspected as an empty bottle of trazodone was found beside her. Obtaining an appropriate history was difficult due to the patient's altered mental status and absence of family members at bedside. The patient was found to have an elevated gamma gap, and further workup was pursued. Subsequently, positive antinuclear antibody (ANA) and anti-double stranded DNA antibody (anti-dsDNA) was detected. During the hospitalization, she was found to meet the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria for systemic lupus erythematosus (SLE). Lumbar puncture with cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, elevated protein with no bacteria and likely a non-infectious process. Magnetic resonance imaging (MRI) spectroscopy of the brain revealed a reversal of normal Hunter's angle, with elevated choline-to-creatine ratio within the white matter, and a lactate peak, which may be present in neuropsychiatric lupus. The patient was diagnosed with SLE with neuropsychiatric manifestations. Consequently, a kidney biopsy was obtained showing Class IV diffuse proliferative glomerulonephritis with fibrillary component likely related to lupus nephritis. The patient was started on treatment for neuropsychiatric lupus, which includes treatment for lupus nephritis with high dose pulse methylprednisolone. The anti-dsDNA titers decreased from 81 to 15 IU/ml and the patient displayed a gradual improvement in her mental status. She was started on cyclophosphamide while inpatient and discharged with the combination of cyclophosphamide, prednisone, along with rheumatology follow-up. This case stresses the importance of ruling out organic causes of AMS before diagnosing patients with a psychiatric disorder. Not every patient with SLE will meet the criteria for diagnosis at the same point in time; hence, it is important to obtain an appropriate history and physical examination to support such diagnosis. We believe our patient had a neuropsychiatric manifestation of SLE, which demonstrates the importance to keep this diagnosis in the list of differentials when assessing a patient presenting with AMS.

Primary Psychiatric Disorder Masking the Diagnosis of Neuropsychiatric Lupus in a Patient with Altered Mental Status: A Case Report

PubMed Central

Perez, Osman; Dave, Kairavee; Prodhan, Tajul; Concepion, Livasky

2017-01-01

Neuropsychiatric systemic lupus erythematosus (NPSLE) has a wide variety of neurologic and psychiatric features. NPSLE symptoms and the psychotic features of primary psychiatric disorders often overlap with each other. These psychotic features often mask and delay the diagnosis of NPSLE. We present the case of a 59-year-old female previously diagnosed with bipolar disorder and generalized anxiety disorder presenting with altered mental status (AMS), subsequently diagnosed with neuropsychiatric lupus. Initially, medication overdose was suspected as an empty bottle of trazodone was found beside her. Obtaining an appropriate history was difficult due to the patient’s altered mental status and absence of family members at bedside. The patient was found to have an elevated gamma gap, and further workup was pursued. Subsequently, positive antinuclear antibody (ANA) and anti-double stranded DNA antibody (anti-dsDNA) was detected. During the hospitalization, she was found to meet the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria for systemic lupus erythematosus (SLE). Lumbar puncture with cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, elevated protein with no bacteria and likely a non-infectious process. Magnetic resonance imaging (MRI) spectroscopy of the brain revealed a reversal of normal Hunter's angle, with elevated choline-to-creatine ratio within the white matter, and a lactate peak, which may be present in neuropsychiatric lupus. The patient was diagnosed with SLE with neuropsychiatric manifestations. Consequently, a kidney biopsy was obtained showing Class IV diffuse proliferative glomerulonephritis with fibrillary component likely related to lupus nephritis. The patient was started on treatment for neuropsychiatric lupus, which includes treatment for lupus nephritis with high dose pulse methylprednisolone. The anti-dsDNA titers decreased from 81 to 15 IU/ml and the patient displayed a gradual improvement in her mental status. She was started on cyclophosphamide while inpatient and discharged with the combination of cyclophosphamide, prednisone, along with rheumatology follow-up. This case stresses the importance of ruling out organic causes of AMS before diagnosing patients with a psychiatric disorder. Not every patient with SLE will meet the criteria for diagnosis at the same point in time; hence, it is important to obtain an appropriate history and physical examination to support such diagnosis. We believe our patient had a neuropsychiatric manifestation of SLE, which demonstrates the importance to keep this diagnosis in the list of differentials when assessing a patient presenting with AMS. PMID:29423350

[Cutaneous lupus erythematosus and skin manifestations in systemic lupus erythematosus].

PubMed

Sticherling, M

2013-06-01

Skin manifestations are frequently observed in lupus erythematosus (LE) and are manifold. Nonspecific and specific symptoms can be differentiated with the latter belonging to the dermatologically well-characterized clinical entities of acute cutaneous, subacute cutaneous, chronic cutaneous as well as intermittent cutaneous LE. These forms are differentially related to systemic LE. Patient history and clinical examinations, laboratory and immunoserological findings as well as organ imaging results determine the time point as well as the intensity of therapy. Apart from cessation of smoking and alcohol consumption as well as stringent UV protection, topical therapy with corticosteroids or calcineurin inhibitors may suffice with limited forms of the disease. In many cases, however, systemic treatment with antimalarial drugs as a basic treatment is mandatory. Several immunosuppressive agents can alternatively be used in conjunction with systemic corticosteroids. Early and effective therapy is important to prevent irreversible scarring of the skin and to avoid internal organ damage.

Echolalia as a novel manifestation of neuropsychiatric systemic lupus erythematosus.

PubMed

Zapor, M; Murphy, F T; Enzenauer, R

2001-01-01

"That tongue of yours, by which I have been tricked, shall have its power curtailed and enjoy the briefest use of speech." With these words, Hera, of Greek mythology, deprived the nymph Echo of spontaneous speech, constraining her instead to merely repeating the words of others. Echolalia, which derives from the word "echo," is disordered speech in which an individual persistently repeats what is heard. Echolalia has been described in patients with a number of neuropsychiatric illnesses including autism and Tourette's syndrome. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a heterogeneous disease with protean manifestations that may occur in approximately 25% to 50% of patients with systemic lupus erythematosus (SLE). Although the most common manifestations include cognitive dysfunction (50%) and seizures (20%), NPSLE may also present as peripheral neuropathy (15%), psychosis (10%), or other central nervous system abnormalities. We report the case of a 57-year-old woman with SLE and echolalia.

Definition and initial validation of a Lupus Low Disease Activity State (LLDAS).

PubMed

Franklyn, Kate; Lau, Chak Sing; Navarra, Sandra V; Louthrenoo, Worawit; Lateef, Aisha; Hamijoyo, Laniyati; Wahono, C Singgih; Chen, Shun Le; Jin, Ou; Morton, Susan; Hoi, Alberta; Huq, Molla; Nikpour, Mandana; Morand, Eric F

2016-09-01

Treating to low disease activity is routine in rheumatoid arthritis, but no comparable goal has been defined for systemic lupus erythematosus (SLE). We sought to define and validate a Lupus Low Disease Activity State (LLDAS). A consensus definition of LLDAS was generated using Delphi and nominal group techniques. Criterion validity was determined by measuring the ability of LLDAS attainment, in a single-centre SLE cohort, to predict non-accrual of irreversible organ damage, measured using the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Consensus methodology led to the following definition of LLDAS: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. Achievement of LLDAS was determined in 191 patients followed for a mean of 3.9 years. Patients who spent greater than 50% of their observed time in LLDAS had significantly reduced organ damage accrual compared with patients who spent less than 50% of their time in LLDAS (p=0.0007) and were significantly less likely to have an increase in SDI of ≥1 (relative risk 0.47, 95% CI 0.28 to 0.79, p=0.005). A definition of LLDAS has been generated, and preliminary validation demonstrates its attainment to be associated with improved outcomes in SLE. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

STAT4 and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus

PubMed Central

Remmers, Elaine F.; Plenge, Robert M.; Lee, Annette T.; Graham, Robert R.; Hom, Geoffrey; Behrens, Timothy W.; de Bakker, Paul I.W.; Le, Julie M.; Lee, Hye-Soon; Batliwalla, Franak; Li, Wentian; Masters, Seth L.; Booty, Matthew G.; Carulli, John P.; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Chen, Wei V.; Amos, Christopher I.; Criswell, Lindsey A.; Seldin, Michael F.; Kastner, Daniel L.

2009-01-01

BACKGROUND Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. METHODS We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. RESULTS A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P = 2.81×10-7; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P = 0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P = 1.87×10-9; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. CONCLUSIONS A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. PMID:17804842

STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus.

PubMed

Remmers, Elaine F; Plenge, Robert M; Lee, Annette T; Graham, Robert R; Hom, Geoffrey; Behrens, Timothy W; de Bakker, Paul I W; Le, Julie M; Lee, Hye-Soon; Batliwalla, Franak; Li, Wentian; Masters, Seth L; Booty, Matthew G; Carulli, John P; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Chen, Wei V; Amos, Christopher I; Criswell, Lindsey A; Seldin, Michael F; Kastner, Daniel L; Gregersen, Peter K

2007-09-06

Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81x10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87x10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. Copyright 2007 Massachusetts Medical Society.

Clinical characteristics during diagnosis of a prospective cohort of patients with systemic lupus erythematosus treated in Spanish Departments of Internal Medicine: The RELES study.

PubMed

Canora, J; García, M; Mitjavila, F; Espinosa, G; Suárez, S; González-León, R; Sopeña, B; Boldova, R; Castro, A; Ruiz-Irastorza, G

Patient registries are useful tools for assessing rare diseases. Our objective is to present the Spanish registry of patients with systemic lupus erythematosus (Registro español de pacientes con lupus eritematoso sistémico, RELES). RELES was started in 2008 as an observational, prospective, multicentre cohort registry that included patients from the time they were diagnosed. The registry's objective is to analyse the incidence and noninflammatory complications of systemic lupus erythematosus (SLE). The departments of internal medicine of 38 Spanish hospitals participate in this registry. A total of 298 patients with a mean age of 40.8±15.7 years were included, 88.9% of whom were women and 85.6% of whom were white. In the first visit, there was a predominance of joint manifestations (74.5%). One hundred and seventy-seven patients (59.4%) were positive for anti-native DNA. In these patients, there was a higher rate of lupus nephritis (26.7% vs. 14%, p=.009; relative risk [RR], 1.33), haemolytic anaemia (13.6% vs. 4.1%, p=.07; RR, 1.46) and lymphopenia (55.4% vs. 43.8%, p=.05; RR, 1.21). The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) score was 9.64 points (interquartile range, 4-13). The patients treated with antimalarial drugs before the diagnosis of SLE had a median SLEDAI score in the first visit of 5, compared with 8 for those who were not treated with these drugs (p=.02). RELES constitutes the first Spanish patient cohort with SLE recorded from the time of the diagnosis. The presence of anti-DNA has been related to severe manifestations such as nephritis and haemolytic anaemia. Treatment with antimalarial drugs before the diagnosis was associated with less active disease at the initial presentation. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

PubMed

Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

2017-06-01

Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving hydroxychloroquine alone.

Anti-dsDNA, anti-nucleosome and anti-C1q antibodies as disease activity markers in patients with systemic lupus erythematosus.

PubMed

Zivković, Valentina; Stanković, Aleksandra; Cvetković, Tatjana; Mitić, Branka; Kostić, Svetislav; Nedović, Jovan; Stamenković, Bojana

2014-01-01

In spite of the growing number of reports on the study of anti-nucleosome and anti-C1q antibodies, there are still controversies on their significance as disease activity markers in patients with systemic lupus erythematosus (SLE) and their use in everyday clinical practice. Our aim was to assess the presence of anti-dsDNA, anti-nucleosome and anti-C1q antibodies in SLE patients, as well as to establish their sensitivity, specificity, positive and negative predictive value, and their correlation with SLE and lupus nephritis clinical activity. The study enrolled 85 patients aged 45.3 +/- 9.7 years on the average, with SLE of average duration 10.37 +/- 7.99 years, hospitalized at the Institute,,Niska Banja" during 2011, and 30 healthy individuals as controls. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). In all examinees the levels of anti-dsDNA, anti-nucleosome and anti-C1q antibodies were measured using the ELISA method with Alegria Test Strips Orgentec (Germany). Patients with active lupus nephritis had a higher presence of anti-C1q antibodies and higher co-positivity of anti-dsDNA, anti-nucleosome, and anti-C1q antibodies compared to those with inactive lupus nephritis (77.77% vs. 21.74%; p < 0.01). SLE patients with SLEDAI > or = 11 had a higher presence of antinucleosome (93.75% vs. 64.15%; p < 0.01) and anti-C1q antibodies (46.87% vs. 22.64%; p<0.05), as well as a higher mean level of anti-nucleosome antibodies (107.79 +/- 83.46 U/ml vs. 57.81 +/- 63.15 U/ml; p < 0.05), compared to those with SLEDAI of 0-10. There was a positive correlation between the SLEDAI and the level of anti-dsDNA (r=0.290; p<0.01), anti-nucleosome (r = 0.443; p < 0.001), and anti-C1q antibodies (r = 0.382; p < 0.001). Only anti-C1q antibodies demonstrated correlation with proteinuria (r = 0.445; p < 0.001). Anti-nucleosome and anti-C1q antibodies demonstrated association with SLE and lupus nephritis activity, suggesting their potential usefulness in making predictions about lupus nephritis and assessment of disease activity.

[B lymphocyte stimulator in systemic lupus erythematosus].

PubMed

Mercado, Ulises

2012-01-01

The B lymphocyte stimulator (BLyS) is an essential protein for the growth and survival of B cells. BLyS is expressed on monocytes, macrophages, and dendritic cells. BLyS binds to three receptors on B cells: BAFF-R, BCMA, and TACI. BLyS overexpression in mice leads to lupus-like syndrome, but not in all, whereas BLyS deficient mice results in a block of B cell development. High serum levels of BLyS can be detected in patients with lupus and rheumatoid arthritis. BLyS antagonists are an attractive target for treating autoimmune diseases.

Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor. alpha. : Relevance to genetic predisposition to systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacob, C.O.; Fronek, Z.; Koo, M.

1990-02-01

The authors report on the production of tumor necrosis factor (TNF)-{alpha} and TNF-{beta} by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of TNF-{alpha}, whereas DR3- and DR4-positive subjects show high levels of TNF-{alpha} production. No correlation between TNF-{alpha} levels and HLA-A, -B, and -C genotype was found. The relevance of this quantitative polymorphism to the genetic predisposition to lupus nephritis in systemic lupus erythematosus (SLE) patients was investigated. DR2, DQw1-positive SLE patients show low levels of TNF-{alpha} inducibility; this genotypemore » is also associated with an increased incidence of lupus nephritis. DR3-positive SLE patients, on the other hand, are not predisposed to nephritis, and these patients have high TNF-{alpha} production. DR4 haplotype is associated with high TNF-{alpha} inducibility and is negatively correlated with lupus nephritis. These data may help explain the strong association between HLA-DR2, DQw1 in SLE patients and their susceptibility to nephritis.« less

Associated Variables of Myositis in Systemic Lupus Erythematosus: A Cross-Sectional Study

PubMed Central

Liang, Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2017-01-01

Background This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). Material/Methods Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). Results The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. Conclusions The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients. PMID:28548078

HPV and systemic lupus erythematosus: a mosaic of potential crossreactions.

PubMed

Segal, Yahel; Dahan, Shani; Calabrò, Michele; Kanduc, Darja; Shoenfeld, Yehuda

2017-04-01

Etiology, pathogenesis, and immunology of systemic lupus erythematosus (SLE) form a complex, still undeciphered picture that recently has been further made complicated by a new factor of morbidity: human papillomaviruses (HPVs). Indeed, a prevalence of HPV infections has been reported among SLE patients. Searching for molecular mechanisms that might underlie and explain the relationship between HPV infection and SLE, we explored the hypothesis that immune responses following HPV infection may crossreact with proteins that, when altered, associate with SLE. Analyzing HPV L1 proteins and using Epstein-Barr virus (EBV) and human retrovirus (HERV) as controls, we found a vast peptide overlap with human proteins comprehending lupus Ku autoantigen proteins p86 and p70, lupus brain antigen 1 homolog, lupus antigen expressed in neurons and muscles, natural killer cell IgG-like receptors, complement proteins C4-A and C4-B, complement receptor CD19, and others. The multitude and heterogeneity of peptide overlaps not only further support the hypothesis that crossreactivity can represent a primum movens in SLE onset, but also provide a molecular framework to the concept of SLE as "an autoimmune mosaic syndrome." Finally, once more, it emerges the need of using the principle of peptide uniqueness as a new paradigm for safe and efficacious vaccinology.

Posterior reversible encephalopathy syndrome in Korean patients with systemic lupus erythematosus: risk factors and clinical outcome.

PubMed

Jung, S M; Moon, S-J; Kwok, S-K; Ju, J H; Park, K-S; Park, S-H; Kim, H-Y

2013-08-01

Posterior reversible encephalopathy syndrome (PRES) is an uncommon neurologic condition associated with systemic lupus erythematosus (SLE). This study aimed to demonstrate the risk factors and clinical outcome of PRES in patients with SLE. Fifteen patients with SLE were diagnosed with PRES by characteristic clinical manifestations and magnetic resonance imaging (MRI) features from 2000 to 2012. Clinical profiles and outcomes were assessed for this study population. Additionally, 48 SLE patients with neurologic symptoms who underwent brain MRI were included for comparative analyses. The median age and duration of SLE in patients with PRES was 27 and 6.1 years, respectively. Comparison between patients with and without PRES revealed significant differences in the presentation of hypertension and seizure, lupus nephritis with renal insufficiency, treatment with high-dose steroid and cyclophosphamide, recent transfusion, and lupus activity measured by SLE disease activity index. Renal failure was the single independent factor with a high odds ratio of 129.250 by multivariate analysis. Of 15 patients, four experienced relapse and two died of sepsis during hospitalization. Our results suggest that lupus nephritis with renal dysfunction and other related clinical conditions can precede the occurrence of PRES in patients with SLE. It is important to perform early brain imaging for a timely diagnosis of PRES when clinically suspected.

B-cell-targeted therapies in systemic lupus erythematosus and ANCA-associated vasculitis: current progress.

PubMed

Md Yusof, Md Yuzaiful; Vital, Edward M J; Emery, Paul

2013-08-01

B cells play a central role in the pathogenesis of systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated vasculitis. There are various strategies for targeting B cells including depletion, inhibition of survival factors, activation and inhibition of co-stimulatory molecules. Controlled trials in systemic lupus erythematosus have shown positive results for belimumab, promising results for epratuzumab and negative results for rituximab. The failure of rituximab in controlled trials has been attributed to trial design, sample size and outcome measures rather than true inefficacy. In anti-neutrophil cytoplasmic antibody-associated vasculitis, rituximab is effective for remission induction and in relapsing disease. However, the optimal long-term re-treatment strategy remains to be determined. Over the next 5 years, evidence will be available regarding the clinical efficacy of these novel therapies, biomarkers and their long-term safety.

Lupus anticoagulant, disease activity and low complement in the first trimester are predictive of pregnancy loss.

PubMed

Mankee, Anil; Petri, Michelle; Magder, Laurence S

2015-01-01

Multiple factors, including proteinuria, antiphospholipid syndrome, thrombocytopenia and hypertension, are predictive of pregnancy loss in systemic lupus erythematosus (SLE). In the PROMISSE study of predictors of pregnancy loss, only a battery of lupus anticoagulant tests was predictive of a composite of adverse pregnancy outcomes. We examined the predictive value of one baseline lupus anticoagulant test (dilute Russell viper venom time) with pregnancy loss in women with SLE. From the Hopkins Lupus Cohort, there were 202 pregnancies from 175 different women after excluding twin pregnancies and pregnancies for which we did not have a first trimester assessment of lupus anticoagulant. We determined the percentage of women who had a pregnancy loss in groups defined by potential risk factors. The lupus anticoagulant was determined by dilute Russell viper venom time with appropriate mixing and confirmatory testing. Generalised estimating equations were used to calculate p values, accounting for repeated pregnancies in the same woman. The age at pregnancy was <20 years (2%), 20-29 (53%), 30-39 (41%) and >40 (3%). 55% were Caucasian and 34% African-American. Among those with lupus anticoagulant during the first trimester, 6/16 (38%) experienced a pregnancy loss compared with only 16/186 (9%) of other pregnancies (p=0.003). In addition, those with low complement or higher disease activity had a higher rate of pregnancy loss than those without (p=0.049 and 0.005, respectively). In contrast, there was no association between elevated anticardiolipin in the first trimester and pregnancy loss. The strongest predictor of pregnancy loss in SLE in the first trimester is the lupus anticoagulant. In addition, moderate disease activity by the physician global assessment and low complement measured in the first trimester were predictive of pregnancy loss. These data suggest that treatment of the lupus anticoagulant could be considered, even in the absence of history of pregnancy loss.

The frequency of and associations with hospitalization secondary to lupus flares from the 1000 Faces of Lupus Canadian cohort.

PubMed

Lee, J; Peschken, C A; Muangchan, C; Silverman, E; Pineau, C; Smith, C D; Arbillaga, H; Zummer, M; Clarke, A; Bernatsky, S; Hudson, M; Hitchon, C; Fortin, P R; Pope, J E

2013-11-01

Hospitalization is a major factor in health care costs and a surrogate for worse outcomes in chronic disease. The aim of this study was to determine the frequency of hospitalization secondary to lupus flare, the causes of hospitalization, and to determine risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). Data were collected as part of the 1000 Canadian Faces of Lupus, a prospective cohort study, where annual major lupus flares including hospitalizations were recorded over a 3-year period. Of 665 patients with available hospitalization histories, 68 reported hospitalization related to a SLE flare over 3 years of follow-up. The average annual hospitalization rate was 7.6% (range 6.6-8.9%). The most common reasons for hospitalization were: hematologic (22.1%), serositis (20.6%), musculoskeletal (MSK) (16.2%), and renal (14.7%). Univariate risk factors for lupus hospitalization included (OR [95% CI]; p < 0.05): juvenile-onset lupus (2.2 [1.1-4.7]), number of ACR SLE criteria (1.4 [1.1-1.7], baseline body mass index (BMI) (1.1 [1.0-1.1]), psychosis (3.4 [1.2-9.9]), aboriginal race (3.2 [1.5-6.7]), anti-Smith (2.6 [1.2-5.4]), erythrocyte sedimentation rate >25 mm/hr (1.9 [1.1-3.4]), proteinuria >0.5 g/d (4.2 [1.9-9.3], and SLAM-2 score (1.1 [1.0-1.2]). After multivariate regression only BMI, number of ACR criteria, and psychosis were associated with hospitalization for lupus flare. The mean annual rate of hospitalization attributed to lupus was lower than expected. Hematologic, serositis, MSK and renal were the most common reasons. In a regression model elevated BMI, more ACR criteria and psychosis were associated with hospitalization.

Current and emerging treatment options in the management of lupus

PubMed Central

Jordan, Natasha; D’Cruz, David

2016-01-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058

Estrogen receptor alpha modulates toll-like receptor signaling in murine lupus

PubMed Central

Cunningham, Melissa A.; Naga, Osama S.; Eudaly, Jackie G.; Scott, Jennifer L.; Gilkeson, Gary S.

2013-01-01

Systemic lupus erythematosus (SLE) is a disease that disproportionately affects females. Despite significant research effort, the mechanisms underlying the female predominance in this disease are largely unknown. Previously, we showed that estrogen receptor alpha knockout (ERαKO) lupus prone female mice had significantly less pathologic renal disease and proteinuria, and significantly prolonged survival. Since autoantibody levels and number and percentage of B/T cells were not significantly impacted by ERα genotype, we hypothesized that the primary benefit of ERα deficiency in lupus nephritis was via modulation of the innate immune response. Using BMDCs and spleen cells/B cells from female wild-type or ERαKO mice, we found that ERαKO-derived cells have a significantly reduced inflammatory response after stimulation with TLR agonists. Our results indicate that the inflammatory response to TLR ligands is significantly impacted by the presence of ERα despite the absence of estradiol, and may partially explain the protective effect of ERα deficiency in lupus-prone animals. PMID:22659029

Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens

PubMed Central

Lech, Maciej; Kulkarni, Onkar P.; Pfeiffer, Stephanie; Savarese, Emina; Krug, Anne; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans-Joachim

2008-01-01

The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of systemic lupus erythematosus (SLE), we generated Sigirr-deficient C57BL/6-lpr/lpr mice. These mice developed a progressive lymphoproliferative syndrome followed by severe autoimmune lung disease and lupus nephritis within 6 mo of age as compared with the minor abnormalities observed in C57BL/6-lpr/lpr mice. Lack of Sigirr was associated with enhanced activation of dendritic cells and increased expression of multiple proinflammatory and antiapoptotic mediators. In the absence of Sigirr, CD4 T cell numbers were increased and CD4+CD25+ T cell numbers were reduced. Furthermore, lack of Sigirr enhanced the activation and proliferation of B cells, including the production of autoantibodies against multiple nuclear lupus autoantigens. These data identify Sigirr as a novel SLE susceptibility gene in mice. PMID:18644972

Retrospective analysis on the impact of tuberculosis on patients with systemic lupus erythematosus (SLE).

PubMed

Zhang, Chang-Ran; Niu, Yuan-Yuan; Lin, Jian-Cong; Wu, Wen-Hui; Li, Ming; Li, Jian-Feng

2013-01-01

Up to now, there have been few reports concerning changes in lupus activity and immune indices of tuberculosis in patients with systemic lupus erythematosis (SLE). A retrospective investigation was given to survey the case data of SLE patients companied with tuberculosis that were treated in our hospital from 2001 to 2010 and compared with that of sex- and age-matched patients with single SLE. Changes in autoantibodies, lupus activity, inflammatory indices, positive rates of tuberculin (PPD) test and tuberculosis antibody (TB-Ab) of both groups were observed. It was indicated by results that ANA antibody level and positive rates of anti-Sm, anti-SSA and anti-SSB antibodies were significantly lower in the TB group than those in the control group (P < 0.05); C3 and C4 levels were significantly higher in the TB group than those in the control group; damage of hematological system (predominantly platelet) was less severe in the TB group than that in the control group (P < 0.05); no significant differences in IgG, IgM and IgA were noted between two groups (P > 0.05); ESR, C-reactive protein and LDH levels were significantly higher in the TB group than those in the control group (P < 0.05); PPD-IgG were significantly higher in the TB group than those in the control group (P < 0.05). These results suggested that after SLE patients were infected with tuberculosis, immune function was altered and lupus activity was inhibited as well.

Follow-up of patients with systemic lupus erythematosus: what is not found in the guidelines.

PubMed

Jiménez-Alonso, J; Vargas-Hitos, J A; Navarrete-Navarrete, N; Zamora-Pasadas, M; Aguilar-Huergo, S; Jáimez, L; Sabio, J M

2013-12-01

A series of measures in the management of patients with systemic lupus erythematosus (SLE) which usually are not found in the lupus guidelines are discussed. In the lupus patient who has been well-controlled in the long term, the dose of hydroxychloroquine should be progressively reduced, without decreasing more than approximately 600 mg per week. We recommend taking this drug in the morning in patients with insomnia, at night in those with dyspepsia and to separate the intake of the drug from the shower (and the water should be as cool as possible) in those patients with aquagenic pruritus. We do not use prednisone on alternate days and exceptionally divide the dose into ¾ before breakfast and ¼ before dinner. Twenty to 30 min should be used per patient in every scheduled visit to assure a good clinical and human practice. We analyzed the follow-up of 112 consecutive patients from our systemic disease unit and found that 71.4% of them had symptoms that were unexplained by lupus and we only referred 8.9% of them to other specialists, probably because of our general training as internal medicine doctors. We suggest that knowing the views of SLE specialists might be of interest since, well-designed studies that would allow to progress in the understanding of this disease could be performed based on their experience. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Socioeconomic status and organ damage in Mexican systemic lupus erythematosus women.

PubMed

Mendoza-Pinto, C; Méndez-Martínez, S; Soto-Santillán, P; Galindo Herrera, J; Pérez-Contreras, I; Macías-Díaz, S; Taboada-Cole, A; García-Carrasco, M

2015-10-01

The objective of this cross-sectional study was to determine relationships between socioeconomic status and organ damage in Mexican systemic lupus erythematosus (SLE) patients. Demographic and clinical variables were assessed. Socioeconomic status was evaluated using the Graffar method and monthly household income. Lupus activity and organ damage were measured using the SLE disease activity scale, validated for the Mexican population (Mex-SLEDAI), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) scale. The 143 Mexican female SLE patients included (mean age 40.1 ± 8.9 years, mean disease duration 8.9 ± 6.3 years) had a mean monthly household income of $ 407.2 ± 326.5. According to the Graffar index, 18.9%, 52.5%, and 28.7% had high/medium-high, medium, and medium-low/low socioeconomic status, respectively. Organ damage was observed in 61 patients (42.7%). Patients with organ damage had lower monthly household incomes ($241.4 ± 152.4 vs. $354.8 ± 288.3) and were more frequently unemployed (57.3% vs. 35.3%; p = 0.01) than those without. Low monthly income was not associated with lupus activity or self-reported health status. In the adjusted multivariate analysis, low monthly income ( < $300) was associated with organ damage. In conclusion, low income may be associated with organ damage in Mexican SLE patients. © The Author(s) 2015.

Expanding the B Cell Centric View of Systemic Lupus Erythematosus

PubMed Central

Morawski, Peter A.; Bolland, Silvia

2017-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a breakdown of self-tolerance in B cells and production of antibodies against nuclear self-antigens. Increasing evidence supports the notion that additional cellular contributors beyond B cells are important for lupus pathogenesis. In this Review, we consider recent advances regarding both pathogenic and regulatory roles of lymphocytes in SLE, beyond the production of IgG autoantibodies. We also discuss various inflammatory effector cell types involved in cytokine production, removal of self-antigens, and responses to autoreactive IgE antibodies. We aim to integrate these ideas to expand the current understanding of the cellular components that contribute to disease progression and ultimately help in the design of novel targeted therapeutics. PMID:28274696

[Systemic lupus erythematosus and anaemia].

PubMed

Falcão, S; Barros, R; Mateus, M; Nero, P; de Matos, A Alves; Pimentão, J Bravo; Ribeiro, I; Weigert, A; Branco, J C

2007-01-01

The authors report the case of a 48-years-old Caucasian women, with a previous diagnosis of systemic lupus erythematosus characterized by asthenia, fever, skin rash, alopecia, Raynaud's phenomenon, arthritis, pericardial effusion, interstitial pulmonary involvement, diffuse proliferative glomerulonephritis with crescents and anemia. The presence of severe anemia refractory to high doses of glucocorticoids (1 mg/ /Kg/day), iron therapy and blood transfusions, associated with a low reticulocyte count determined the execution of a bone marrow aspiration, biopsy and immunophenotyping, which were compatible with the diagnosis of Myelodysplastic Syndrome. The treatment with erythropoietin (5.000U 3x/week) and cyclophosphamide pulses (1 gr/m(2) month) induced complete regression of morphologic bone marrow changes and anemia. The main causes of anemia in lupus patients are discussed.

Sweet's syndrome associated with systemic lupus erythematosus: a case report and review of the literature.

PubMed

Tsuji, Hideaki; Yoshifuji, Hajime; Nakashima, Ran; Imura, Yoshitaka; Yukawa, Naoichiro; Ohmura, Koichiro; Miyagawa-Hayashino, Aya; Kabashima, Kenji; Mimori, Tsuneyo

2013-08-01

A 35-year-old Japanese female patient with systemic lupus erythematosus (SLE) presented with fever, erythematous papules and nodules, and polyarthralgia. Skin biopsy of a nodule was compatible with Sweet's syndrome. The papules/nodules were well treated with an oral glucocorticoid. Thirty cases of Sweet's syndrome associated with lupus erythematosus (LE) have been reported in the published work. The mean age was 34.2 years. They showed a higher male ratio (male : female, 1:2) compared with patients with SLE (1:9) and Sweet's syndrome (1:3.7). Sweet's syndrome may occur as a manifestation of LE, and a moderate dose of an oral glucocorticoid will result in a good response. © 2013 Japanese Dermatological Association.

Lupus erythematosus: considerations for dentistry.

PubMed

De Rossi, S S; Glick, M

1998-03-01

Lupus erythematosus, or LE, is a connective tissue disease that affects a number of organ systems. Patients with this condition can experience several other serious conditions--bleeding, infection, endocarditis, adrenal insufficiency and mucocutaneous disease--that can affect the provision of dental care. The authors describe considerations for managing dental treatment of patients with LE.

Organic brain syndrome with psychosis as an initial manifestation of systemic lupus erythematosus in an elderly woman.

PubMed

Mavrikakis, M E; Antoniades, L G; Germanides, J B; Sotou, D; Rassidakis, A

1992-01-01

This paper describes a rare case of organic brain syndrome with psychosis and clinically transverse myelopathy, as initial manifestations of systemic lupus erythematosus in an elderly woman. The identification and evaluation of antibodies to ribosome P in the serum and cerebrospinal fluid may be of help in such cases for differential diagnosis. The patient was treated successfully with 30 mg prednisone daily.

Association between academic performance and cognitive dysfunction in patients with juvenile systemic lupus erythematosus.

PubMed

Frittoli, Renan Bazuco; de Oliveira Peliçari, Karina; Bellini, Bruna Siqueira; Marini, Roberto; Fernandes, Paula Teixeira; Appenzeller, Simone

2016-01-01

To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE). Patients aged ≤18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR) recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC). The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p<0.05) was adopted. 41 patients with a mean age of 14.5±2.84 years were included. Cognitive dysfunction was noted in 17 (41.46%) patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p=0.039). Anxiety symptoms were observed in 8 patients (19.51%) and were associated with visual perception (p=0.037) and symptoms of depression were observed in 1 patient (2.43%). Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

[Depressive disorder in Mexican pediatric patients with systemic lupus erythematosus (SLE)].

PubMed

Carbajal-Alonso, Hilda Lilian; García-Moreno, Norberta Prisilia; Rodríguez-Arreola, Brenda; Barrera de León, Juan Carlos

2016-01-01

To identify the prevalence of depression in Mexican pediatric patients with systemic lupus erythematosus. Analytical transversal study including patients aged 7-16 years with a diagnosis of systemic lupus erythematosus seen at the Pediatric Rheumatology Consultation Service. The disease was classified by means of the MEX-SLEDAI questionnaire. Descriptive statistics with central tendency and dispersion and comparative measurements with chi-squared and Mann-Whitney U tests. Logistic regression and association with odds ratios. SPSS v.21.0 statistical software package. We evaluated 45 patients who presented depression, n=9 (20%), including eight females (89%) and one male (11%), median age 13 years (range, 7-16) in children with depression vs. 13 years (range, 9-14) p=0.941, depression more frequent in schoolchildren. Habitual residence, disease evolution time, and duration of the immunosuppressor did not show a significant difference between both groups. Divorced parents p=0.037. Neuropsychiatric manifestations of lupus presented in 2.2% of all patients and in 100% of patients with depression. Disease activity index (MEX-SLEDAI) did not demonstrate a relationship with the presence of depression. Prevalences in pediatric populations are less that that reported in adults, association with disease activity, evolution time, and immunosuppressor use and duration not found.

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Tuberculoid leprosy masquerading as systemic lupus erythematosus: an interesting observation.

PubMed

Zawar, Vijay; Kumavat, Shrikant; Pawar, Manoj; Desai, Dipti

2017-09-01

Leprosy is a chronic granulomatous infectious multisystem disease that may present with protean manifestations. It mimics many systemic and dermatological disorders. Here we report a case in which an elderly female presented with malar rash, intermittent fever, and arthralgia. Her diagnosis was significantly delayed due to a close clinical resemblance to systemic lupus erythematosus. It is important to be aware of such manifestations of leprosy and improve awareness of it in clinicians to avoid misdiagnosis and delay in treatment.

[Modulating the survival and maturation system of B lymphocytes: Current and future new therapeutic strategies in systemic lupus erythematosus].

PubMed

Valor, Lara; López-Longo, Francisco Javier

2015-09-07

Systemic lupus erythematosus is an autoimmune disease associated with an aberrant production of autoantibodies by self-reactive B lymphocytes. The study of the phenotypic characteristics of B lymphocytes and the identification of their surface receptors such as BAFF-R, TACI and BCMA, which are responsible of their survival and maturation, have contributed to the development of new therapeutic strategies in recent years. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Blisters and Loss of Epidermis in Patients With Lupus Erythematosus

PubMed Central

Merklen-Djafri, Carine; Bessis, Didier; Frances, Camille; Poulalhon, Nicolas; Debarbieux, Sébastien; Cordel, Nadège; Lipsker, Dan

2015-01-01

Abstract The nosology of bullous lesions or equivalents (vesicles, erosions, and crusts) in patients with lupus erythematosus (LE) is rarely addressed. The primary aim of this study was to draw up a precise phenotypic inventory of such skin lesions; the secondary objective was to assess a potential relationship between the different types of loss of epidermis and extracutaneous lupus manifestations. We conducted a retrospective multicenter study including 22 patients with definite LE and bullous lesions or equivalents. All biopsies were reviewed. Patients were recruited in the dermatology departments of 6 centers. Patients were included if they met the diagnosis of systemic LE according to American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics criteria or diagnosis of cutaneous LE based on classic clinical criteria and/or histological ascertainment of LE. Patients were recruited through clinician's memory and photographic collections. Three clinico-pathological patterns could be individualized. First, toxic epidermal necrolysis (TEN)-like, sheet-like, skin detachment; sun-exposure, mild mucosal involvement, and dermal mucin deposition allow differential diagnosis with classical Lyell syndrome. Second, vesiculo-bullae and/or crusting occurring on typical lesions of subacute cutaneous lupus erythematosus or chronic cutaneous lupus erythematosus. Third, tense vesicles and/or blisters with an underlying neutrophilic dermatosis and a usual response to dapsone. A careful analysis of 22 LE patients with epidermal detachment reveals 2 main pathomechanisms: a classic LE interface dermatitis, which can be hyperacute and lead to TEN-like skin detachment; and a neutrophilic dermatosis, with tense vesicles and/or blisters, including classic bullous LE. PMID:26579826

Side effects unrelated to disease activity and acceptability of highly effective contraceptive methods in women with systemic lupus erythematosus: a randomized, clinical trial.

PubMed

Cravioto, María-del-Carmen; Jiménez-Santana, Luisa; Mayorga, Julio; Seuc, Armando H

2014-08-01

To assess the side effects unrelated to disease activity and the acceptability of combined oral contraceptives (COCs), progestin-only pills (POPs) and copper-releasing intrauterine devices (IUDs) in women with systemic lupus erythematosus (SLE). A randomized clinical trial including 162 women with SLE, assigned to COC (n=54), POP (n=54) or IUD (n=54). Follow-up visits were conducted after 1, 2, 3, 6, 9 and 12 months of treatment to monitor the presence of symptoms, changes in body weight and blood pressure as well as the development of health problems other than those relating to lupus. Reasons for discontinuation and satisfaction with the use of the assigned method were recorded at the end of treatment. Statistical analysis included descriptive statistics, repeated measure analyses and Kaplan-Meier curves. Significantly different discontinuation rates due to any reason [35%, 55%, 29% (p<0.01)] or nonmedical reasons [(11%, 31%, 4% (p<0.05)] were observed among the COC, POP and IUD groups. Nausea was most frequent among COC users, dysmenorrhea among IUD users and acne and hirsutism among POP users. Mean blood pressures remained unchanged. Mild increases in body weight were observed over time in all treatment groups. Most women were satisfied with the use of the assigned contraceptive method. Oral contraceptives and IUD are acceptable birth control methods for patients with lupus, when counseling and specialized health attention are provided; however, the acceptability of POP appears to be inferior. Side effects unrelated to lupus disease activity are not frequent reasons to discontinue the contraceptive methods. This study delves into an area that has not been explored among patients with lupus. Our findings on the associated side effects and reasons for discontinuing COCs, POPs or copper-bearing IUDs may be useful in improving contraceptive counseling for women with lupus. Furthermore, they also heighten our knowledge on the reasons that may preclude the widespread use of effective contraceptives among lupus patients. Copyright © 2014. Published by Elsevier Inc.

Rituximab in the treatment of shrinking lung syndrome in systemic lupus erythematosus.

PubMed

Peñacoba Toribio, Patricia; Córica Albani, María Emilia; Mayos Pérez, Mercedes; Rodríguez de la Serna, Arturo

2014-01-01

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. We report the case of a patient with non-responding SLS (neither to glucocorticoids nor immunosupresors), who showed remarkable improvement after the onset of treatment with rituximab. Although there is a little evidence, treatment with rituximab could be proposed in SLS when classical treatment fails. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Systemic lupus, folie a trois and homicide.

PubMed

Caribé, André C; Daltro-Oliveira, Renato; Araújo, Ricardo Henrique; Cardoso, Ana Paula; Guimarães, Paulo Barreto; Miranda-Scippa, Angela; Quarantini, Lucas C

2013-10-01

Folie a trois is a syndrome characterized by the transfer of delusional ideas from one person to two other persons. This condition rarely ends in the murder of any involved and we are unaware of where the primary case had the diagnosis of acute psychosis in systemic lupus erythematosus (SLE). We present a case report of folie a trois resulting in murder, secondary to acute psychosis in SLE. Copyright © 2013 Elsevier Inc. All rights reserved.

Organic brain syndrome with psychosis as an initial manifestation of systemic lupus erythematosus in an elderly woman.

PubMed Central

Mavrikakis, M E; Antoniades, L G; Germanides, J B; Sotou, D; Rassidakis, A

1992-01-01

This paper describes a rare case of organic brain syndrome with psychosis and clinically transverse myelopathy, as initial manifestations of systemic lupus erythematosus in an elderly woman. The identification and evaluation of antibodies to ribosome P in the serum and cerebrospinal fluid may be of help in such cases for differential diagnosis. The patient was treated successfully with 30 mg prednisone daily. PMID:1540015

Management of massive diffuse alveolar hemorrhage in a child with systemic lupus erythematosus.

PubMed

Kimura, Dai; Shah, Samir; Briceno-Medina, Mario; Sathanandam, Shyam; Haberman, Brent; Zhang, Jie; Myers, Linda; Kumar, Tk Susheel; Knott-Craig, Christopher

2015-01-01

Diffuse alveolar hemorrhage (DAH) from systemic lupus erythematosus (SLE) is a rare but potentially life-threatening condition. We report the case of a 14-year-old female with SLE who developed hypoxia and shock secondary to severe alveolar hemorrhage. She was successfully managed by placement on extracorporeal membrane oxygenation (ECMO) followed by emergent pulmonary lobectomy and medical treatment including high-dose methylprednisolone, cyclophosphamide, intravenous immunoglobulin, and plasmapheresis.

Breast vasculitis in association with breast gigantism in a pregnant patient with systemic lupus erythematosus.

PubMed Central

Propper, D J; Reid, D M; Stankler, L; Eastmond, C J

1991-01-01

A 24 year old woman with systemic lupus erythematosus (SLE) developed widespread necrotic skin ulceration and gigantism of both breasts during an exacerbation of SLE in the last trimester of her second pregnancy. Over the remainder of the pregnancy the ulceration was only controlled by high dose corticosteroids. After parturition, however, it was possible to reduce the steroid dose without recurrence of the ulceration. Images PMID:1888201

Will studies in individuals with systemic lupus erythematosus be the key to future HIV vaccine design?

PubMed

Bonsignori, Mattia

2014-11-01

The induction of HIV-1 broadly neutralizing antibodies (bnAbs) remains the primary goal of a preventive HIV-1 vaccine but no HIV-1 vaccine candidate has succeeded in inducing bnAbs. All the bnAbs isolated from chronically HIV-1 infected subjects display one or more traits associated with control by host tolerance and immunoregulatory mechanisms, including reactivity against self antigens. Recent studies on a HIV-1 patient with concurrent systemic lupus erythematosus have informed on how similar bnAbs are to typical autoantibodies controlled by immune tolerance mechanisms. Future studies aimed at elucidating the intersection between autoantibodies generated in the context of systemic lupus erythematosus and the development of HIV-1 bnAbs will further our knowledge of specific roadblocks that hamper the production of bnAbs and, ultimately, inform us on how to implement vaccine strategies to circumvent them.

[Hematopoietic steam cell transplantation in the management of systemic lupus erythematosus resistant to treatment].

PubMed

Rojas Ramos, Enrique; Martínez Jiménez, Norma E; Reyes Salina, Alfredo

2004-01-01

Recently stem cell transplantation has been suggested like novel treatment in some severe auto-immune diseases, specifically in severe and refractory to conventional treatment in systemic lupus erythematosus patients. Autologus hematopoietic steam cell transplantation has been used in systemic lupus erythematosus, because it does not represent risk of development in graft versus host disease, which is the most common and severe complication in alogenic transplant. This type of transplant is poorly used because of the difficulty to get donors and laboratory background. Patients under this type of treatment received high dosage of chemotherapy, followed by alogenic hematopoietic steam cell transplantation with or without T cell depletion. Most of cases have successes in treatment and some patients get clinical and serological remission even for 34 months. However, a longer following is necessary to obtain concluding results. This paper reviews those treatments in clinical cases reported in the literature.

Role of Angiography in Systemic Lupus Erythematosus-Induced Choroiditis.

PubMed

Lee, Kenneth Rohan; Peng, Lai Yin; Iqbal, Tajunisah Begum; Subrayan, Visvaraja

2017-03-31

To report a case of systemic lupus erythematosus-induced choroidal vasculitis. A 34-year-old woman with a long-standing history of systemic lupus erythematosus had a sudden painless loss of vision in the right eye over 12 hours. Ocular examination revealed a visual acuity of counting fingers of 1 foot on the right eye and 20/20 on the left. There was a relative afferent pupillary defect on the right side with a pink, distinct optic disk margin. Optical coherence tomography of the macula and fundus fluorescein angiogram for the eyes were normal. The MRI brain and orbit with the cerebral MRA did not show signs of optic neuritis or occipital vasculitic changes. However, the indocyanine green angiography revealed patches of ill-defined areas of choroidal hypofluorescence in the early- to mid-phase in the macula region. ICGA becomes the crucial tool in unmasking the presence of choroidal vasculitis.

BILAG-2004 index captures systemic lupus erythematosus disease activity better than SLEDAI-2000.

PubMed

Yee, C-S; Isenberg, D A; Prabu, A; Sokoll, K; Teh, L-S; Rahman, A; Bruce, I N; Griffiths, B; Akil, M; McHugh, N; D'Cruz, D; Khamashta, M A; Maddison, P; Zoma, A; Gordon, C

2008-06-01

To assess the reliability of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 index in routine practice and its ability to capture disease activity as compared with the British Isles Lupus Assessment Group (BILAG)-2004 index. Patients with systemic lupus erythematosus from 11 centres were assessed separately by two raters in routine practice. Disease activity was assessed using the BILAG-2004 and SLEDAI-2000 indices. The level of agreement for items was used to assess the reliability of SLEDAI-2000. The ability to detect disease activity was assessed by determining the number of patients with a high activity on BILAG-2004 (overall score A or B) but low SLEDAI-2000 score (<6) and number of patients with low activity on BILAG-2004 (overall score C, D or E) but high SLEDAI-2000 score (>or=6). Treatment of these patients was analysed, and the increase in treatment was used as the gold standard for active disease. 93 patients (90.3% women, 69.9% Caucasian) were studied: mean age was 43.8 years, mean disease duration 10 years. There were 43 patients (46.2%) with a difference in SLEDAI-2000 score between the two raters and this difference was >or=4 in 19 patients (20.4%). Agreement for each of the items in SLEDAI-2000 was between 81.7 and 100%. 35 patients (37.6%) had high activity on BILAG-2004 but a low SLEDAI-2000 score, of which 48.6% had treatment increased. There were only five patients (5.4%) with low activity on BILAG-2004 but a high SLEDAI-2000 score. SLEDAI-2000 is a reliable index to assess systemic lupus erythematosus disease activity but it is less able than the BILAG-2004 index to detect active disease requiring increased treatment.

Association of large intergenic noncoding RNA expression with disease activity and organ damage in systemic lupus erythematosus.

PubMed

Wu, Yanfang; Zhang, Feifei; Ma, Jianyang; Zhang, Xiaoyan; Wu, Lingling; Qu, Bo; Xia, Shiwei; Chen, Shunle; Tang, Yuanjia; Shen, Nan

2015-05-21

Despite growing evidence that large intergenic noncoding RNAs (lincRNAs) can regulate gene expression and widely take part in normal physiological and disease conditions, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. The aim of this study was to detect the levels of four lincRNAs (ENST00000500949: linc0949, ENST00000500597: linc0597, ENST00000501992: linc1992, and ENST00000523995: linc3995) involved in innate immunity in the peripheral blood mononuclear cells (PBMCs) of patients with SLE and correlate these lincRNA levels with disease activity, organ damage, clinical features and medical therapies. PBMCs were obtained from 102 patients with SLE, 54 patients with rheumatoid arthritis (RA) and 76 healthy donors. lincRNA expression levels were measured by real-time quantitative polymerase chain reaction. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, and organ damage was evaluated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. linc0949 and linc0597 were significantly decreased in patients with SLE compared with patients with RA and healthy control subjects. linc0949 was correlated with SLEDAI-2K score (r = -0.329, P = 0.0007), as well as with complement component C3 level (r = 0.348, P = 0.0003). The level of linc0949 was also reduced in patients with SLE who had the presence of cumulative organ damage. In addition, decreasing expression of linc0949 was associated with lupus nephritis. linc0949 expression significantly increased after treatment, whereas neither disease activity nor organ damage correlated with linc0597 expression. Our results provide novel empirical evidence that linc0949 could be a potential biomarker for diagnosis, disease activity and therapeutic response in SLE.

Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus.

PubMed

Liu, Chau-Ching; Manzi, Susan; Kao, Amy H; Navratil, Jeannine S; Ruffing, Margie J; Ahearn, Joseph M

2005-10-01

There is an urgent need for biomarkers with which to monitor disease activity in patients with systemic lupus erythematosus (SLE). We recently showed that abnormal levels of C4d, an activation-derived fragment of complement component C4, are deposited on the surface of erythrocytes from patients with SLE. This study focused on reticulocytes, the youngest and shortest-lived erythrocytes (lifespan 24-48 hours), with the objective of testing our hypothesis that when reticulocytes emerge from the bone marrow, they are immediately exposed to and acquire C4d at levels proportionate to the extent of complement activation at that time, thereby reflecting disease activity in SLE. We conducted a cross-sectional study of 156 patients with SLE, 140 patients with other diseases, and 159 healthy controls. Levels of C4d on the surface of reticulocytes were examined using a 2-color flow cytometric assay. The results were analyzed for correlations with SLE disease activity. A wide range of increased levels of reticulocyte C4d was specifically detected in SLE patients. These levels fluctuated in SLE patients and correlated with clinical disease activity, as determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus Activity Measure (SLAM). Specifically, in cross-sectional analyses, patients with reticulocyte C4d levels in the highest quartile compared with those in the lowest quartile had significantly higher SELENA-SLEDAI (P = 0.00002) and SLAM (P = 0.02) scores. Longitudinal observation demonstrated that the reticulocyte C4d levels changed in relation to the clinical course in individual patients. These findings support our hypothesis that C4d-bearing reticulocytes may serve as biomarkers of disease activity in patients with SLE.

The validity and reliability of Systemic Lupus Erythematosus Quality of Life Questionnaire (L-QoL) in a Turkish population.

PubMed

Duruöz, M T; Unal, C; Toprak, C Sanal; Sezer, I; Yilmaz, F; Ulutatar, F; Atagündüz, P; Baklacioglu, H S

2017-12-01

Background Systemic lupus erythematosus (SLE) may have a profound impact on quality of life. There is increasing interest in measuring quality of life in lupus patients. The purpose of this study was to investigate the validity and reliability of SLE Quality of Life Questionnaire (L-QoL) in Turkish SLE patients. Methods SLE according to 2012 Systemic Lupus International Collaborating Clinics Classification Criteria were recruited into the study. Demographic data, clinical parameters and disease activity measured with the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K); were noted. Nottingham Health Profile and Health Assessment Questionnaire were filled out in addition to the Turkish L-QoL (LQoL-TR). Internal consistency, test-retest reliability, and convergent and discriminant validity were evaluated. Results The mean age of participants was 43.55 ± 14.33 years and the mean disease duration was 89.8 ± 92.1 months. The patients filled out LQoL-TR in 2.5 min. Strong correlation of LQoL-TR with all subgroups of the Nottingham Health Profile and the Health Assessment Questionnaire were established showing the convergent validity. The highest correlation was demonstrated with emotional reactions (rho = 0.72) and sleep component (rho = 0.65) of the Nottingham Health Profile scale ( p < 0.0001). Its poor and not significant correlation with nonfunctional parameters (age, disease duration, perceived general health, SLEDAI-2K) showed its discriminative properties. LQoL-TR demonstrated good internal reliability with a Cronbach's α of 0.93 and test-retest reliability with intraclass correlation coefficient of 0.87. Conclusion The LQoL-TR is a practical and useful tool which demonstrates good validity and reliability.

Combined mepacrine-hydroxychloroquine treatment in patients with systemic lupus erythematosus and refractory cutaneous and articular activity.

PubMed

Ugarte, A; Porta, S; Ríos, R; Martinez-Zapico, A; Ortego-Centeno, N; Agesta, N; Ruiz-Irastorza, G

2018-01-01

Aim The aim of this study was to evaluate the clinical response to combined therapy with hydroxychloroquine and mepacrine in patients with systemic lupus erythematosus and refractory joint and/or skin disease. Methods Mepacrine was added to 46 systemic lupus erythematosus patients unresponsive to treatment with the following drug combinations: hydroxychloroquine + prednisone + immunosuppressive drugs ( n = 24), hydroxychloroquine + prednisone ( n = 16), hydroxychloroquine + prednisone + retinoids ( n = 2), hydroxychloroquine alone ( n = 1), hydroxychloroquine + one immunosuppressive drug ( n = 1), hydroxychloroquine + prednisone + one immunosuppressive drug + belimumab ( n = 1) or hydroxychloroquine + prednisone + belimumab ( n = 1). The outcome variable was the clinical response, either complete or partial, based on clinical judgement. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score were additionally used. Results A total of 91% patients showed complete/partial response, with similar rates among those with joint or skin disease. In patients with cutaneous activity, a statistically significant decrease in the CLASI was seen. There also was a statistically significant decrease in the SLEDAI. The mean daily dose of prednisone decreased from 5.8 to 3.4 mg/d ( p = 0.001). Prednisone could be discontinued in 20% of patients. No serious adverse events were seen. Smoking was the only predictor of complete response. Conclusion In the setting of refractory skin and/or joint disease, the addition of mepacrine to previous therapy including hydroxychloroquine was safe and effective in reducing disease activity and decreasing prednisone doses. The fact that smokers responded better opens the door to further studying the combination of mepacrine-hydroxychloroquine as a first-line therapy in such patients.

Hypernephroma Presenting with Cutaneous Leukocytoclastic Vasculitis and Lupus Anticoagulant: Resolution after Nephrectomy

PubMed Central

Murray, Nigel P.; Ruíz, Amparo; Reyes, Eduardo

2012-01-01

Hypernephroma can present as a variety of paraneoplastic, nonmetastatic conditions, including vasculitis, and rarely a lupus-type anticoagulant. Nephrectomy leads to the resolution of the systemic complaints. Malignancy, in this case hypernephroma, can present as an immune-mediated paraneoplastic syndrome which resolves after removal of the underlying tumor. PMID:22919534

Chronic cutaneous lupus erythematosus presenting as periorbital edema and erythema.

PubMed

Cyran, S; Douglass, M C; Silverstein, J L

1992-02-01

We report two unusual cases of cutaneous lupus erythematosus presenting as dramatic eyelid edema and erythema. Neither patient had evidence of systemic or other significant cutaneous involvement. The eyelid edema and erythema were unilateral in one case and bilateral in the other. Both cases responded to therapy with antimalarial drugs.

Complement-fixing properties of antinuclear antibodies distinguish drug-induced lupus from systemic lupus erythematosus.

PubMed

Rubin, R L; Teodorescu, M; Beutner, E H; Plunkett, R W

2004-01-01

The immunofluorescence antinuclear antibody (ANA) test has been widely used to monitor autoimmune disease, but its value for diagnostic purposes is compromised by low specificity and high prevalence in disease-free individuals. The capacity of autoantibodies to fix serum complement proteins when bound to antigen is an important effector function because this property is associated with acute and chronic inflammatory processes. The current study evaluates the complement-fixing properties of antinuclear antibodies (CANA) in three well-defined and clinically-related patient groups: systemic lupus erythematosus (SLE), drug-induced lupus (DIL) and drug-induced autoimmunity (DIA). Of 20 patients diagnosed with SLE, 90% displayed complement-fixing ANA while this feature was present in only two of 18 patients with DIL and no patients with DIA without associated disease even though the mean ANA titres were similar among these patient groups. CANA was significantly correlated with anti-Sm activity. Because SLE but not DIL or DIA can be a life-threatening disease associated with complement consumption in vivo, these results demonstrate that measurement of CANA is a diagnostically useful tool and may have immunopathologic implications.

Mapping lupus susceptibility genes in the NZM2410 mouse model.

PubMed

Morel, Laurence

2012-01-01

Considerable efforts have been deployed over the years to decipher the genetic basis of systemic lupus erythematosus (SLE). The NZM2410 strain is murine model in which the genetic analysis of SLE is the most advanced. NZM2410 studies have shown that, as in SLE patients, lupus susceptibility is achieved by the coexpression of many susceptibility alleles, each of which with a small contribution to the overall disease phenotype. This mouse model has also revealed the critical role played by gene-gene interactions, which are believed to be an essential contribution to human SLE heritability, although it has been much more difficult to characterize. We have now reached a phase in which NZM2410 susceptibility genes have been identified, all them novel in their association with lupus or even with immune functions. Ongoing studies geared at understanding how these genes impact immune tolerance and interact with each other in the mouse, and their impact on the human immune system or target organs, will undoubtedly lead to important discovery for a better understanding on the disease and potential identification of therapeutic targets. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies.

PubMed

Cortés-Hernández, J; Ordi-Ros, J; Paredes, F; Casellas, M; Castillo, F; Vilardell-Tarres, M

2002-06-01

Our aim was to assess the outcome of pregnancy in a cohort of patients with SLE and to evaluate clinical and laboratory markers for fetal outcome and maternal flares. Sixty patients with 103 pregnancies were evaluated prospectively between 1984 and 1999. There were 68 live births, 15 spontaneous abortions, 12 stillbirths and eight therapeutic abortions. Of liveborn infant births, 19 were premature, 24 had suffered intrauterine growth restriction and one had neonatal lupus. Maternal lupus flares occurred in 33% of pregnancies, mostly in the second trimester (26%) and in the post-partum period (51%). Flares during pregnancy showed a statistically significant association with discontinuation of chloroquine treatment, a history of more than three flares before gestation, and a SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score of >or=5 in these flares. Antiphospholipid antibodies, C3 hypocomplementaemia and hypertension during pregnancy were significantly associated with fetal loss, prematurity and intrauterine growth restriction. Patients with more active SLE and those with aPL antibodies and hypertension should be monitored and managed carefully during pregnancy.

Hydroxychloroquine in systemic lupus erythematosus (SLE).

PubMed

Ponticelli, C; Moroni, G

2017-03-01

Hydroxychloroquine (HCQ) is an alkalinizing lysosomatropic drug that accumulates in lysosomes where it inhibits some important functions by increasing the pH. HCQ has proved to be effective in a number of autoimmune diseases including systemic lupus erythematosus (SLE). Areas covered: In this review the mechanisms of action, the efficacy, and the safety of HCQ in the management of patients with SLE have been reviewed. HCQ may reduce the risk of flares, allow the reduction of the dosage of steroids, reduce organ damage, and prevent the thrombotic effects of anti-phospholipid antibodies. The drug is generally safe and may be prescribed to pregnant women. However, some cautions are needed to prevent retinopathy, a rare but serious complication of the prolonged use of HCQ. Expert opinion: HCQ may offer several advantages not only in patients with mild SLE but can also exert important beneficial effects in lupus patients with organ involvement and in pregnant women. The drug has a low cost and few side effects. These characteristics should encourage a larger use of HCQ, also in lupus patients with organ involvement.

Advances in the treatment of cutaneous lupus erythematosus.

PubMed

Kuhn, A; Landmann, A; Wenzel, J

2016-07-01

Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE. © The Author(s) 2016.

Drug-Induced by Systemic Lupus Erythematosus Presenting as Recurrent Pericardial Effusion After Mitral Valve Repair.

PubMed

Haydari, Aghigh; Sabzi, Feridoun; Dabiri, Samsam; Poormotaabed, Alireza

2017-09-01

We report a patient presented with recurrent pericardial effusion caused by drug-induced systemic lupus Erythematosus (SLE) following mitral valve repair. The surgery was complicated by hemiparesis and convulsion in early postoperative period. The patient had been received carbamazepine for a paroxysmal seizure that occurred following mitral valve repair. The post operative computed tomography showed embolic stroke and its sequel (seizure) that treated with carbamazepine. In the 3rd month of follow-up, however, hemiparesis recovered by physiotherapy but carbamazepine was not discontinued as by request of neurologist. In the 6th month of surgery, the patient admitted by dyspnea and massive pericardial effusion that treated by subxiphoid drainage. This event was re occurred in two times in a short time frame and each event treated by surgical approach. The serologic exam in the last admission revealed drug-induced lupus erythematosus. The carbamazepine as an anti convulsive drug has been described to cause LE like disease in multiple case reports. Laboratory exam exhibited the possibility of carbamazepine-induced lupus in our case, with the extremely rare presentation of recurrent massive pericardial effusion.

Low capacity of erythrocytes to bind with immune complexes via C3b receptor in patients with systemic lupus erythematosus: correlation with pathological proteinuria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nojima, Y.; Terai, C.; Minota, S.

1985-01-01

Erythrocytes from 51 patients with systemic lupus erythematosus and 75 controls were tested for the capacity to bind aggregated human gamma-globulin labeled with radioiodine in the presence of complement. Both in patients and controls, a trimodal distribution of binding capacity was observed. Low (less than 9% of the added radioactivity), intermediate (9-17%), and high binding (more than 17%) were observed in 13, 58, and 29% in controls and in 49, 43 and 8% in lupus patients. The low binding capacity of erythrocytes persisted even after patients entered remission following steroid therapy. A genetic control of binding capacity was supported bymore » familial surveys. Prevalence of pathological proteinuria was significantly higher in patients with low binding capacity than those with intermediate or high binding capacity (16/25 vs 7/26, P less than 0.01). These results indicate that an impaired physiological disposal of immune complexes via the erythrocyte C3b receptor in lupus patients may contribute to the development of renal involvement.« less

Emerging new pathways of pathogenesis and targets for treatment in systemic lupus erythematosus and Sjogren's syndrome.

PubMed

Perl, Andras

2009-09-01

Systemic lupus erythematosus (SLE) and Sjogren's syndrome are chronic inflammatory diseases characterized by the dysfunction of T cells, B cells, and dendritic cells and the production of antinuclear autoantibodies. Here, we evaluate newly discovered molecular and cellular targets for the treatment of SLE and Sjogren's syndrome. The mammalian target of rapamycin in T and B cells has been successfully targeted for treatment of SLE with rapamycin or sirolimus both in patients and animal models. Inhibition of oxidative stress, nitric oxide production, interferon alpha, toll-like receptors 7 and 9, histone deacetylase, spleen tyrosine kinase, proteasome function, lysosome function, endosome recycling, and the nuclear factor kappa B pathway showed efficacy in animal models of lupus. B-cell depletion and blockade of anti-DNA antibodies and T-B cell interaction have shown success in animal models, whereas human studies have so far failed to accomplish clinical endpoints, possibly due to inadequacies in study design. Discovery of novel genes and signaling pathways in lupus pathogenesis offers novel biomarker-targeted approaches for treatment of SLE and Sjogren's syndrome.

Lupus and leprosy: beyond the coincidence.

PubMed

Ribeiro, F M; Gomez, V E; Albuquerque, E M N; Klumb, E M; Shoenfeld, Y

2015-02-01

Systemic lupus erythematous (SLE) is an autoimmune disease that presents an increased susceptibility to infections which may trigger reactivation. Disease flares have been mostly associated with parvovirus B19, cytomegalovirus, EBV and Mycobacterium tuberculosis infections, but it is probable that many other agents may also induce innate and adaptive immune system stimulation including the production of autoantibodies as ANA, anti nDNA and anti-ß2-GPI mainly in lepromatous leprosy. Mycobacterium leprae not only may determine symptoms that mimic lupus flares, including autoantibodies production, but could also act as a trigger for lupus reactivation; however, its association is still not fully explored. As demonstrated for tuberculosis, it is quite possible that molecular mimicry may also be involved in the interface of these two diseases. Some studies reported shared epitopes among idiotypes derived from 8E7 and TH9 lepromatous antibodies and those obtained from SLE patients, and it could partially explain the triggering phenomenon of SLE caused by M. leprae. We report and discuss three Brazilian patients whose disease was inactive and presented disease flares concurrently with the diagnosis of leprosy.

The curiously suspicious: a role for Epstein-Barr virus in lupus.

PubMed

Harley, J B; Harley, I T W; Guthridge, J M; James, J A

2006-01-01

While the events initiating the development of autoantibodies in systemic lupus erythematosus (SLE) have not yet been convincingly established, newly developed tools for molecular investigation make such an undertaking increasingly practical. Applied to the earliest events in the sequence culminating in lupus autoimmunity, we present a critical potential role for Epstein-Barr virus (EBV) in the development and perhaps perpetuation of SLE. The expected properties for an environmental risk factor for SLE are found in this virus and the human host response against it. Existing data show the molecular progression to autoimmunity observed in SLE patient sera, the discovery of the first autoimmune epitopes in the Sm and Ro autoantigen systems, and the possible emergence of these autoantibodies from the heterologous antibodies against Epstein-Barr nuclear antigen-1 (EBNA-1). Further, existing data demonstrate association of SLE with EBV infection, even preceding the development of autoimmunity. Finally, the data are consistent with a proposed model of lupus pathogenesis that begins with antibodies to EBNA-1, predisposing to immune responses that develop crossreactive autoantibodies that culminate in the development of SLE autoimmunity.

Lupus nephritis remission, albeit with positive anti-doping test.

PubMed

Jakez-Ocampo, Juan; Richaud-Patin, Yvonne; Llorente, Luis

2007-01-01

A 39-year-old woman developed systemic lupus erythematosus with nephropathy after a holiday in Jamaica. She was prescribed with prednisone, azathioprine and aspirin. As she was obsessed with aesthetic procedures, she decided not to take the prescription. Instead, she took her bodybuilding trainer's advice of one intramuscular injection of stanozolol for 10 weeks in order to increase her gluteus area. One week after finishing the latter regimen, there was no disease activity. Whether lupus remission in this patient was spontaneous or a consequence of stanozolol administration will remain a riddle for this fortunate outcome.

Lots of autoantibodies equal lupus?

PubMed Central

2013-01-01

Autoantibodies may be found years before an autoimmune disease becomes clinically apparent. For systemic lupus erythematosus (SLE), those to RNA-binding proteins, to phospholipids, and to double-stranded DNA, in particular, have been found in sera of SLE patients years before the diagnosis was made. New data now show in an unbiased way that, in patients with early SLE, no single antibody class or specificity is associated with progression to SLE. Rather, an increasing number of autoantibody specificities, such as to thyroid antigens, was observed in patients progressing. This points to more generalized B cell autoreactivity during progression to SLE, underlying lupus disease manifestations. PMID:23347779

Autoantibodies as Biomarkers for the Prediction of Neuropsychiatric Events in Systemic Lupus Erythematosus

PubMed Central

Hanly, J G; Urowitz, M B; Su, L; Bae, S-C; Gordon, C; Sanchez-Guerrero, J; Clarke, A; Bernatsky, S; Vasudevan, A; Isenberg, D; Rahman, A; Wallace, D J; Fortin, P R; Gladman, D; Dooley, M A; Bruce, I; Steinsson, K; Khamashta, M; Manzi, S; Ramsey-Goldman, R; Sturfelt, G; Nived, O; van Vollenhoven, R; Ramos-Casals, M; Aranow, C; Mackay, M; Kalunian, K; Alarcón, G S; Fessler, B J; Ruiz-Irastorza, G; Petri, M; Lim, S; Kamen, D; Peschken, C; Farewell, V; Thompson, K; Theriault, C; Merrill, J T

2015-01-01

Objective Neuropsychiatric (NP) events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. We examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrollment predicted subsequent NP events. Methods Patients with recent SLE diagnosis were assessed prospectively for up to 10 years for NP events using ACR case definitions. Decision rules of graded stringency determined whether NP events were attributable to SLE. Associations between the first NP event and baseline autoantibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results Disease duration at enrollment was 5.4±4.2 months, followup 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 ≥1 NP event (total 917 events). NP events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrollment 21.9% of patients had lupus anticoagulant, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. Lupus anticoagulant at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (Hazard ratio, HR 2.54 (95% CI: 1.08–5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR: 3.92 (95% CI:1.23–12.5); p=0.02). Other autoantibodies did not predict NP events. Conclusion In a prospective study of 1047 recently diagnosed SLE patients, lupus anticoagulant and anti-ribosomal P antibodies are associated with an increased future risk for intracranial thrombosis and lupus psychosis respectively PMID:21893582

Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus.

PubMed

Bertoli, A M; Vilá, L M; Reveille, J D; Alarcón, G S

2008-04-01

To determine the features associated with acute onset systemic lupus erythaematosus (SLE). A total of 631 SLE patients from LUMINA (for "lupus in minority populations: nature vs nurture"), a multiethnic (Hispanics, African-Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of > or = 4 American College of Rheumatology (ACR) criteria for the classification of SLE in < or = 4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortality, autoantibodies, HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (chi(2) and Student t test) and multivariable (stepwise logistic regression) analyses. A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076-3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005-1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956-0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827-0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249-0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142-0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE.

Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus

PubMed Central

Bertoli, A M; Vilá, L M; Reveille, J D; Alarcón, G S

2009-01-01

Objective To determine the features associated with acute onset systemic lupus erythaematosus (SLE). Methods A total of 631 SLE patients from LUMINA (for “lupus in minority populations: nature vs nurture”), a multiethnic (Hispanics, African–Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of ≥4 American College of Rheumatology (ACR) criteria for the classification of SLE in ≤4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortally, autoantibodies. HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (χ2 and Student t test) and multivariable (stepwise logistic regression) analyses. Results A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076–3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005–1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956–0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827–0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249–0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142–0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. Conclusions Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE. PMID:17720721

Eumycotic mycetoma caused by Cladophialophora bantiana in a patient with systemic lupus erythematosus.

PubMed

Werlinger, Kelly D; Yen Moore, Angela

2005-05-01

We present the case of a 31-year-old patient who developed widespread mycetoma across her back and shoulders caused by Cladophialophora bantiana 16 years after injury to those sites from tornado debris. The patient also had a history of systemic lupus erythematosus treated with systemic steroids. Systemic antifungal treatment with fluconazole and itraconazole proved ineffective, and surgical debridement was required. Nine other culture-confirmed cases of cutaneous infection with this organism have been reported worldwide. This type of infection can occur in immunocompromised or immunocompetent patients, and may respond to systemic antifungals or surgery.

Expanding the B Cell-Centric View of Systemic Lupus Erythematosus.

PubMed

Morawski, Peter A; Bolland, Silvia

2017-05-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a breakdown of self-tolerance in B cells and the production of antibodies against nuclear self-antigens. Increasing evidence supports the notion that additional cellular contributors beyond B cells are important for lupus pathogenesis. In this review we consider recent advances regarding both the pathogenic and the regulatory role of lymphocytes in SLE beyond the production of IgG autoantibodies. We also discuss various inflammatory effector cell types involved in cytokine production, removal of self-antigens, and responses to autoreactive IgE antibodies. We aim to integrate these ideas to expand the current understanding of the cellular components that contribute to disease progression and ultimately help in the design of novel, targeted therapeutics. Published by Elsevier Ltd.

Genetic Factors in Systemic Lupus Erythematosus: Contribution to Disease Phenotype

PubMed Central

Ceccarelli, Fulvia; Perricone, Carlo; Borgiani, Paola; Ciccacci, Cinzia; Rufini, Sara; Cipriano, Enrica; Alessandri, Cristiano; Spinelli, Francesca Romana; Sili Scavalli, Antonio; Novelli, Giuseppe; Valesini, Guido; Conti, Fabrizio

2015-01-01

Genetic factors exert an important role in determining Systemic Lupus Erythematosus (SLE) susceptibility, interplaying with environmental factors. Several genetic studies in various SLE populations have identified numerous susceptibility loci. From a clinical point of view, SLE is characterized by a great heterogeneity in terms of clinical and laboratory manifestations. As widely demonstrated, specific laboratory features are associated with clinical disease subset, with different severity degree. Similarly, in the last years, an association between specific phenotypes and genetic variants has been identified, allowing the possibility to elucidate different mechanisms and pathways accountable for disease manifestations. However, except for Lupus Nephritis (LN), no studies have been designed to identify the genetic variants associated with the development of different phenotypes. In this review, we will report data currently known about this specific association. PMID:26798662

Oral Ulcers in Juvenile-Onset Systemic Lupus Erythematosus: A Review of the Literature.

PubMed

Rodsaward, Pongsawat; Prueksrisakul, Titipong; Deekajorndech, Tawatchai; Edwards, Steven W; Beresford, Michael W; Chiewchengchol, Direkrit

2017-12-01

Oral ulcers are the most common mucosal sign in juvenile-onset systemic lupus erythematosus (JSLE). The ulcers are one of the key clinical features; however, the terminology of oral ulcers, especially in JSLE patients, is often vague and ill-defined. In fact, there are several clinical manifestations of oral ulcers in JSLE, and some lesions occur when the disease is active, indicating that early management of the disease should be started. Oral ulcers are classified as lupus erythematosus (LE) specific, where the lesional biopsy shows a unique pattern of mucosal change in LE, and LE nonspecific, where the ulcers and their histopathological findings can be found in other oral diseases. Here, the clinical manifestations, diagnosis and management of oral ulcers in JSLE patients are reviewed.

Mitral Valve Surgery in Patients with Systemic Lupus Erythematosus

PubMed Central

Hekmat, Manouchehr; Ghorbani, Mohsen; Ghaderi, Hamid; Majidi, Masoud; Beheshti, Mahmood

2014-01-01

Valvular heart disease is the common cardiac manifestation of systemic lupus erythematosus (SLE) with a tendency for mitral valve regurgitation. In this study we report a case of mitral valve replacement for mitral stenosis caused by Libman-Sacks endocarditis in the setting of SLE. In addition, we provide a systematic review of the literature on mitral valve surgery in the presence of Libman-Sacks endocarditis because its challenge on surgical options continues. Surgical decision depends on structural involvement of mitral valve and presence of active lupus nephritis and antiphospholipid antibody syndrome. Review of the literature has also shown that outcome is good in most SLE patients who have undergone valvular surgery, but association of antiphospholipid antibody syndrome with SLE has negative impact on the outcome. PMID:25401131

Fatal acute pancreatitis complicated by pancreatic pseudocysts in a patient with systemic lupus erythematosus.

PubMed

Cairoli, Ernesto; Pérez, Gerardo; Briva, Arturo; Cancela, Mario; Alonso, Juan

2010-03-01

Pancreatitis is a relatively rare but severe manifestation in systemic lupus erythematosus (SLE) patients. We report a case of a 39-year-old woman with previous SLE diagnose treated with prednisone and mycophenolate mofetil who developed an acute pancreatitis complicated by pancreatic pseudocysts within the context of a severe lupus flare. Elevated serum amylase and computerized tomography confirmed the diagnosis and mechanical obstruction or toxic-metabolic etiologies were ruled out. In the present case, we opted for the clinical surveillance of pancreatic pseudocyst and not perform invasive medical procedures to drainage. A steroid therapy was started in order to achieve SLE and pancreatitis remission, however, it was unable to avoid the development of multiorgan failure and patient died a few days after diagnosis was made.

A Case of Intractable Hemophagocytic Syndrome Associated with Systemic Lupus Erythematosus Resistant to Corticosteroids and Intravenous Cyclophosphamide that Was Successfully Treated with Cyclosporine A.

PubMed

Toko, Hirofumi; Tsuboi, Hiroto; Umeda, Naoto; Honda, Fumika; Ohyama, Ayako; Takahashi, Hidenori; Abe, Saori; Yokosawa, Masahiro; Asashima, Hiromitsu; Hagiwara, Shinya; Hirota, Tomoya; Kondo, Yuya; Matsumoto, Isao; Sumida, Takayuki

2018-05-18

Hemophagocytic syndrome (HPS) associated with systemic lupus erythematosus (SLE), dubbed acute lupus hemophagocytic syndrome (ALHS), is an intractable complication of SLE. A 24-year-old man who had been diagnosed with SLE three months previously, presented with fever, rash, hallucination, and pancytopenia accompanied with hyperferritinemia and bone marrow hemophagocytosis. He was diagnosed with ALHS and neuropsychiatric (NP)-SLE. Although 4 courses of methylprednisolone pulse therapy and 1 course of intravenous cyclophosphamide (IVCY) improved his NP-SLE, his ALHS did not respond. However, the addition of cyclosporine A (CsA) led to a rapid remission from ALHS. This suggests the usefulness of CsA in the treatment of intractable, corticosteroid- and IVCY-resistant ALHS.

Antibodies and the brain: antiribosomal P protein antibody and the clinical effects in patients with systemic lupus erythematosus.

PubMed

González, Alfonso; Massardo, Loreto

2018-06-01

Analysis of antiribosomal P protein autoantibodies (anti-P) pathogenicity in diffuse brain manifestations of neuropsychiatric lupus, emphasizing cognitive dysfunction and the recently emerged role of cross-reacting neuronal surface P antigen (NSPA) in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-Methyl-D-Aspartate receptor glutamatergic transmission. Circulating anti-P antibodies associate with executive planning dysfunction and attention impairments in lupus patients and perturb glutamatergic transmission through NSPA in mice hippocampus, translating into impaired synaptic plasticity and spatial memory. Planning impairment impacts quality of life. In addition to the known association with lupus psychosis, new clinical and experimental evidence reveal a pathogenic role of anti-P antibodies in cognitive dysfunction, mechanistically explained by the anti-P interaction with NSPA as a target involved in glutamatergic synaptic plasticity.

Methyl salicylate 2-O-β-d-lactoside alleviates the pathological progression of pristane-induced systemic lupus erythematosus-like disease in mice via suppression of inflammatory response and signal transduction

PubMed Central

He, Yang-Yang; Yan, Yu; Zhang, Hui-Fang; Lin, Yi-Huang; Chen, Yu-Cai; Yan, Yi; Wu, Ping; Fang, Jian-Song; Yang, Shu-Hui; Du, Guan-Hua

2016-01-01

Systemic lupus erythematosus (SLE), with a high incidence rate and insufficient therapy worldwide, is a complex disease involving multiple organs characterized primarily by inflammation due to deposition of immunocomplexes formed by production of autoantibodies. The mechanism of SLE remains unclear, and the disease still cannot be cured. We used pristane to induce SLE in female BALB/c mice. Methyl salicylate 2-O-β-d-lactoside (MSL; 200, 400, and 800 mg/kg) was orally administered 45 days after pristane injection for 4.5 months. The results showed that MSL antagonized the increasing levels of multiple types of antibodies and cytokines in lupus mice. MSL was found to suppress joint swelling and have potent inhibitory effect on arthritis-like symptoms. MSL also significantly decreased the spleen index and expression of inflammatory markers in the lupus mice. MSL protected the kidneys of lupus mice from injury through inhibiting the expression of inflammatory cytokines and reducing the IgG and C3 immunocomplex deposits. Further Western blot assays revealed that the downregulation of the intracellular inflammatory signals of NFκB and JAK/STAT3 might be the potential molecular mechanisms of the pharmacological activity of MSL against SLE in vivo. These findings may demonstrate that MSL has the potential to be a useful and highly effective treatment for SLE. PMID:27729775

Pregnancy in Women with Systemic Lupus Erythematosus: A Retrospective Study of 83 Pregnancies at a Single Centre

PubMed Central

Chen, Shanying; Sun, Xuejuan; Wu, Bide; Lian, Xuejian

2015-01-01

Objective: To evaluate the outcome of 80 pregnant women with systemic lupus erythematosus (SLE) and explore the risk factors for lupus flare, obstetric complications and fetal loss. Methods: 83 pregnancies in 80 women were divided into three groups. Group A: patients in remission for > 6 months before pregnancy, proteinuria < 0.5 g per day, without renal failure and discontinuation of cytotoxic drugs for > one year; Group B: patients with SLE disease activity in the six months before pregnancy; Group C: patients with new onset SLE during pregnancy. Results: In group A, 76.47% pregnancies achieved full-term deliveries and 80.39% achieved live born infants. In group B and C, the outcome was poor. Among 62 patients (64 pregnancies) diagnosed as SLE before pregnancy, SLE flares occurred in 27 (42.19%) pregnancies. SLE disease activity in the six months before pregnancy was significantly associated with lupus flare (OR 5.00, 95% CI 1.14–21.87, p = 0.03) and fetal loss. New onset lupus during pregnancy was independently associated with obstetric complications (OR 7.22, 95% CI 2.14–24.38, p = 0.001). Conclusions: The current study confirmed the previous report that SLE should be considered a high risk of pregnancy. If pregnancy is planned after remission for > 6 months, the favorable outcome can be achieved. PMID:26295404

Work disability in Argentinian patients with systemic lupus erythematosus is prevalent and it is due to ethnic, socioeconomic and disease-related factors.

PubMed

Pisoni, Cecilia N; Muñoz, Sebastián A; Tamborenea, María N; García, Mercedes; Curti, Ana; Cappuccio, Ana; Rillo, Oscar; Imamura, Patricia M; Schneeberger, Emilce; Ballent, Marcela; Cousseau, Mario L; Velasco Zamora, Jorge; Saurit, Verónica; Toloza, Sergio; Danielsen, María C; Bellomio, Verónica I; Graf, Cesar; Paira, Sergio; Cavallasca, Javier; Pons Estel, Bernardo; Moreno, José L C; Díaz, Mónica; Alba, Paula; Verando, Marcela; Tate, Guillermo; Mysler, Eduardo; Sarano, Judith; Civit, Emma E; Risueño, Fabián; Álvarez Sepúlveda, Pablo; Larroude, María S; Méndez, Marcos F; Conforti, Andrea; Sohn, Débora

2018-04-02

To study the prevalence and the associated factors of work disability (WD) in systemic lupus erythematosus (SLE) patients. A sample of 419 SLE patients from an observational cross-sectional multicenter study was included. Sociodemographic features, disease characteristics, comorbidities, quality of life, unhealthy behaviors, and work-related factors were measured in a standardized interview. Work disability was defined by patient self-report of not being able to work because of SLE. To identify variables associated with work disability, two different multivariate regression models using a stepwise backward method were performed. Prevalence of WD due to SLE was 24.3%. Eighty-nine percent were female and 51% were Caucasians. Mean disease duration was 8.9 ± 7.2 years, and median System Lupus International Collaborating Clinics/American College of Rheumatology damage index SLICC-SDI was 1.5 (range 0-17). In stepwise multivariate logistic regression, living below the poverty line (odds ratio [OR] = 4.65), less than 12 years of education (OR = 2.84), Mestizo ethnicity (OR = 1.94) and SLICC-SDI (OR = 1.25) were predictors of WD. A second model was performed including patient-derived measures; in this model sedentary lifestyle (OR = 2.69) and lower emotional health domain score of the Lupus Quality of Life (LupusQoL) questionnaire (OR = 1.03) were found to be associated to WD and a higher score in LupusQoL physical health domain (OR = 0.93) was protective. The prevalence of WD in Argentinian SLE patients was 24.3%. WD was associated with ethnic (Mestizo), socioeconomic (poverty) and disease-related factors. Patient-related outcomes such us sedentary lifestyle and poor emotional quality of life were also associated with WD. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Lupus

MedlinePlus

... Staying Safe Videos for Educators Search English Español Lupus KidsHealth / For Teens / Lupus What's in this article? ... dad that she might have lupus. What Is Lupus? Lupus (pronounced: LOO-pus) is a disease that ...

Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice.

PubMed

Moon, Jae-Seung; Mun, Chin Hee; Kim, Jung-Ho; Cho, Jen-Young; Park, Sung-Dong; Park, Tae-Yoon; Shin, Jin-Su; Ho, Chun-Chang; Park, Yong-Beom; Ghosh, Sankar; Bothwell, Alfred L M; Lee, Sang-Won; Lee, Sang-Kyou

2018-05-01

Excessive expression of Tbet and IFNγ is evidence of systemic lupus erythematosus (SLE) in lupus patients. In this study, the nucleus-transducible form of Transcription Modulation Domain (TMD) of Tbet (ntTbet-TMD), which is a fusion protein between Protein Transduction Domain Hph-1 (Hph-1-PTD) and the TMD of Tbet comprising DNA binding domain and isotype-specific domain, was generated to inhibit Tbet-mediated transcription in the interactomic manner. ntTbet-TMD was effectively delivered into the nucleus of the cells and specifically inhibited Tbet-mediated transcription without influencing the differentiation of other T cell subsets and signaling events for T cell activation. The severity of nephritis was significantly reduced by ntTbet-TMD as effectively as methylprednisolone in lupus-prone mice. The number of Th1, Th2 or Th17 cells and the secretion of their cytokines substantially decreased in the spleen and kidney of lupus-prone mice by ntTbet-TMD treatment. In contrast to methylprednisolone, the marked increase of Treg cells and the secretion of their immunosuppressive cytokine were detected in the spleen of (NZB/NZW) F1 mice treated with ntTbet-TMD. Thus, ntTbet-TMD can improve nephritis in lupus-prone mice by modulating the overall proinflammatory microenvironment and rebalancing T cell subsets, leading to new immune therapeutics for Th1-mediated autoimmune diseases. Copyright © 2017 International Society of Nephrology. All rights reserved.

Diagnosing Lupus

MedlinePlus

... Lupus.org Sign Up for Our Newsletter Donate Diagnosing Lupus Learn about lab tests, lupus symptoms, and how ... doctor's appointment article Reducing time to diagnosis blog Diagnosing lupus Getting a lupus diagnosis is challenging. Here’s what ...

Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study.

PubMed

Yuan, Mo; Tan, Ying; Pang, Yun; Li, Yong-Zhe; Song, Yan; Yu, Feng; Zhao, Ming-Hui

2017-11-01

Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort. One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed. Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p < .001). The serum levels of anti-PTX3 auto-antibodies were negatively correlated with proteinuria in lupus nephritis (r = -.143, p = .047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207 ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (<3.207 ng/ml) and with anti-PTX3 auto-antibodies (4.79 (3.39-8.28) versus 3.95 (1.78-7.0), p = .03; 168.84 ± 153.63 versus 101.44 ± 47.36, p = .01; 34.1% (14/41) versus 0% (0/9), p = .04; respectively). Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.

Disruption of Pathogenic Cellular Networks by IL-21 Blockade Leads to Disease Amelioration in Murine Lupus

PubMed Central

Choi, Jin-Young; Seth, Abhinav; Kashgarian, Michael; Terrillon, Sonia; Fung, Emma; Huang, Lili; Wang, Li Chun; Craft, Joe

2017-01-01

Systemic lupus erythematosus (SLE, lupus) is characterized by autoantibody-mediated organ injury. Follicular helper T cells (Tfh) orchestrate physiological germinal center (GC) B cell responses, while in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell-derived autoantibody production. IL-21, a Tfh cell-derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as SLE. We used blockade of IL-21 to dissect the mechanisms by which this cytokine promotes autoimmunity in murine lupus. Treatment of lupus-prone B6.Sle1.Yaa mice with an anti-IL-21 blocking antibody reduced titers of autoantibodies, delayed progression of glomerulonephritis and diminished renal infiltrating Tfh and T helper 1 (Th1) cells, and improved overall survival. Therapy inhibited excessive accumulation of Tfh cells co-expressing IL-21 and IFN-γ, and suppressed their production of the latter cytokine, albeit while not affecting their frequency. Anti-IL-21 treatment also led to a reduction in GC B cells, CD138hi plasmablasts, IFN-γ-dependent IgG2c production, and autoantibodies, indicating that Tfh-cell derived IL-21 is critical for pathological B cell cues in lupus. Normalization of GC responses were, in part, due to uncoupling of Tfh-B cell interactions, as evidenced by reduced expression of CD40L on Tfh cells and reduced B cell proliferation in treated mice. Our work provides mechanistic insight into the contribution of IL-21 to the pathogenesis of murine lupus, while revealing the importance of T-B cellular cross-talk in mediating autoimmunity, demonstrating that its interruption impacts both cell types leading to disease amelioration. PMID:28219887

A case of systemic lupus erythematosus presenting transverse myelitis after an episode of meningitis.

PubMed

Yago, Toru; Tateishi, Mutsuto; Ichikawa, Naomi; Furuya, Takefumi; Sakurai, Tadashi; Nakajima, Hiroshi; Hara, Masako; Kamatani, Naoyuki

2005-01-01

A 27-year-old woman suffering from systemic lupus erythematosus was admitted because she had motor and sensory palsy of the lower extremities, neck stiffness, and a fever. Cerebrospinal fluid study indicated meningitis, and magnetic resonance imaging revealed cord swelling and high signals at Th9-Th12 levels. Antibiotics treatment led to resolution of the meningeal signs. Intravenous cyclophosphamide and prednisolone resulted in a partial recovery from the transverse myelitis neurological disturbance.

Systemic lupus erythematosus with Sjögren's syndrome and renal tubular acidosis presenting as nephrogenic diabetes insipidus.

PubMed

Parrey, Ashaq Hussain; Ahmad, Fayaz; Ahmad, Mushtaq; Basher, Adil

2018-01-01

Systemic lupus erythematosus (SLE) presenting as diabetes insipidus (DI) is a rare association; there is a case report of neurogenic DI in patients of SLE; however, SLE and nephrogenic DI has not been reported in literature. We present a case of SLE presenting as nephrogenic DI. We report a case who presented with DI (nephrogenic) and fulfilled criteria for SLE and Sjögren's syndrome with renal tubular acidosis.

Multisystemic diseases and ethnicity: a focus on lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease.

PubMed

Petit, A; Dadzie, O E

2013-10-01

We present an overview of the association between ethnicity and the clinical and epidemiological aspects of four multisystemic diseases: lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease. In particular, we highlight observed ethnic differences in cutaneous manifestations of these diseases. This article should help guide clinical management, as well as serve to highlight future areas for research. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Anti-NR2A/B Antibodies and Other Major Molecular Mechanisms in the Pathogenesis of Cognitive Dysfunction in Systemic Lupus Erythematosus

PubMed Central

Tay, Sen Hee; Mak, Anselm

2015-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately 1–45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS), collectively termed neuropsychiatric systemic lupus erythematosus (NPSLE), remains one of the important causes of death in these patients. Cognitive dysfunction is one of the most common manifestations of NPSLE, which comprises deficits in information-processing speed, attention and executive function, in conjunction with preservation of speech. Albeit a prevalent manifestation of NPSLE, the pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances in genetic studies, molecular techniques, neuropathology, neuroimaging and cognitive science have gleaned valuable insights into the pathophysiology of lupus-related cognitive dysfunction. In recent years, a role for autoantibodies, molecular and cellular mechanisms in cognitive dysfunction, has been emerging, challenging our previous concept of the brain as an immune privileged site. This review will focus on the potential pathogenic factors involved in NPSLE, including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B) antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro-inflammatory mediators. Better understanding of these mechanistic processes will enhance identification of new therapeutic modalities to halt the progression of cognitive decline in SLE patients. PMID:25955648

New insights into the pathogenesis and management of lupus in children.

PubMed

Midgley, A; Watson, L; Beresford, M W

2014-06-01

Systemic lupus erythematosus (SLE) is the archetypal systemic autoimmune disease, characterised by inflammation causing a wide spectrum of major clinical manifestations that may affect any organ. Childhood-onset SLE (cSLE) is more severe with greater damage and drug burden than adult-onset SLE. Understanding the pathogenesis of cSLE is a key step in directing medical management. The dysregulated immune system, that in health is usually vital in protecting the body from infection, contributes significantly to the disease process. Improved knowledge of disease mechanism will help to identify potential targets for novel agents and the identification of new biomarkers of disease activity. This review will present current knowledge of the innate and adaptive immune responses in cSLE and the optimal patient management that aims to control the disease. Innate immune dysregulation includes the overexpression of interferon-α, dendritic cell activation, neutrophil extracellular traps and phagocyte abnormalities. The classical adaptive immune system is over activated in lupus with excessive autoantibody production due to abnormalities in B and T cell regulation. Novel biologic medications are being developed to specifically target these areas with the ultimate aim of improving the long-term outlook and quality of life for children living with Lupus. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of the ACR and SLICC classification criteria in juvenile-onset systemic lupus erythematosus: a longitudinal analysis.

PubMed

Lythgoe, H; Morgan, T; Heaf, E; Lloyd, O; Al-Abadi, E; Armon, K; Bailey, K; Davidson, J; Friswell, M; Gardner-Medwin, J; Haslam, K; Ioannou, Y; Leahy, A; Leone, V; Pilkington, C; Rangaraj, S; Riley, P; Tizard, E J; Wilkinson, N; Beresford, M W

2017-10-01

Objectives The Systemic Lupus International Collaborating Clinics (SLICC) group proposed revised classification criteria for systemic lupus erythematosus (SLICC-2012 criteria). This study aimed to compare these criteria with the well-established American College of Rheumatology classification criteria (ACR-1997 criteria) in a national cohort of juvenile-onset systemic lupus erythematosus (JSLE) patients and evaluate how patients' classification criteria evolved over time. Methods Data from patients in the UK JSLE Cohort Study with a senior clinician diagnosis of probable evolving, or definite JSLE, were analyzed. Patients were assessed using both classification criteria within 1 year of diagnosis and at latest follow up (following a minimum 12-month follow-up period). Results A total of 226 patients were included. The SLICC-2012 was more sensitive than ACR-1997 at diagnosis (92.9% versus 84.1% p < 0.001) and after follow up (100% versus 92.0% p < 0.001). Most patients meeting the SLICC-2012 criteria and not the ACR-1997 met more than one additional criterion on the SLICC-2012. Conclusions The SLICC-2012 was better able to classify patients with JSLE than the ACR-1997 and did so at an earlier stage in their disease course. SLICC-2012 should be considered for classification of JSLE patients in observational studies and clinical trial eligibility.

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXI. Disease activity, damage accrual, and vascular events in pre- and postmenopausal women.

PubMed

Fernández, Mónica; Calvo-Alén, Jaime; Alarcón, Graciela S; Roseman, Jeffrey M; Bastian, Holly M; Fessler, Barri J; McGwin, Gerald; Vilá, Luis M; Sanchez, Martha L; Reveille, John D

2005-06-01

To determine the differences in clinical manifestations, disease activity, damage accrual, and medication use in systemic lupus erythematosus (SLE) patients as a function of menopausal status at disease onset. Women with SLE as per the criteria of the American College of Rheumatology, with disease duration of 6 months, and/or oophorectomy, and/or increased follicle-stimulating hormone values for reproductive-age women, and/or treatment with hormone replacement therapy. Patients were divided into premenopausal and postmenopausal categories. Socioeconomic status, cumulative clinical manifestations, disease activity (at study entry or time 0, last visit, and over time), as measured by the Systemic Lupus Activity Measure, and damage accrual, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (at time 0 and at last visit) were compared between the 2 groups of women. Multivariable models were then examined making adjustments for all possible known confounders. Dependent variables in the models were renal involvement, damage accrual, arterial vascular events, and venous thrombosis. Five hundred eighteen women from the LUMINA cohort were included; 436 (84.2%) were premenopausal and 82 (15.8%) were postmenopausal. Disease onset after menopause was more common among Caucasians. Renal involvement was more common in premenopausal women, whereas vascular arterial events were more frequent in postmenopausal women. All other disease manifestations, as well as disease activity, were comparable between both groups. The presence of damage accrual at time 0 and study end was more frequent in postmenopausal women. Age, rather than menopausal status, independently contributed to damage accrual, renal involvement, and vascular arterial events in these women. A hypoestrogenemic state secondary to menopause appears not to be protective against disease activity and damage accrual. Age rather than menopausal status is a strong independent predictor of damage accrual and of vascular events in women with lupus.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa

PubMed Central

Lewandowski, Laura B; Schanberg, Laura E; Thielman, Nathan; Phuti, Angel; Kalla, Asgar A; Okpechi, Ikechi; Nourse, Peter; Gajjar, Priya; Faller, Gail; Ambaram, Priya; Reuter, Helmuth; Spittal, Graeme; Scott, Christiaan

2016-01-01

Background Systemic Lupus Erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE (pSLE) on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa (SA). Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serologic characteristics was extracted from medical records. Results were compared to a well-described North American pSLE cohort. Results Seventy-two SA patients were enrolled in the study; mean age 11.5 years, 82% female. The racial distribution was 68% Coloured, 24% Black, 5% White, and 3% Asian/Indian. Most patients presented with severe lupus nephritis (LN) documented by renal biopsy (61%). Of patients with LN, 63% presented with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate, and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K [SLEDAI-2K] 20.6). The SLEDAI-2K at enrollment in the PULSE cohort (5.0) did not differ from the North American pSLE cohort (4.8). Sixty three % of PULSE cohort had end organ damage with System Lupus International Collaborating Clinic-Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, 9 (13%) developed ESRD with 6 (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrollment in the SA registry. SA patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study reveals a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population. PMID:27488473

Soluble Mediators and Clinical Features Discern Risk of Transitioning to Classified Disease in Relatives of Systemic Lupus Erythematosus Patients

PubMed Central

Munroe, Melissa E.; Young, Kendra A.; Kamen, Diane L.; Guthridge, Joel M.; Niewold, Timothy B.; Costenbader, Karen H.; Weisman, Michael H.; Ishimori, Mariko L.; Wallace, Daniel J.; Gilkeson, Gary S.; Karp, David R.; Harley, John B.; Norris, Jill M.; James, Judith A.

2016-01-01

Objective Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential to curtail irreversible inflammatory damage. The objective of this study was to identify factors associated with transition to classified disease that inform SLE risk. Methods Previously identified lupus patient blood relatives with < 4 American College of Rheumatology SLE classification criteria at baseline (n=409) were enrolled in this follow-up study. Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEE) were applied to identify factors anticipating disease transition. Results Forty-five relatives (11%) transitioned to classified SLE during follow-up (mean time=6.4 years). Relatives who transitioned displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (p<0.0001) at baseline than non-transitioned relatives. Importantly, they also had elevated baseline plasma levels of inflammatory mediators, including B-lymphocyte stimulator (BLyS), stem cell factor (SCF), and interferon-associated chemokines (p≤0.02), with concurrent decreases in levels of regulatory mediators, tumor growth factor (TGF)-β and interleukin (IL)-10 (p≤0.03). GEE revealed that baseline SLE-CSQ or ACR scores and plasma levels of SCF and TGF-β (p≤0.03), but not autoantibodies, were significant and independent predictors of SLE transition. Conclusions Altered levels of soluble mediators anticipate transition to classified disease in lupus relatives. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials. PMID:27863174

Renal biopsy pathology in a cohort of patients from southwest Sydney with clinically diagnosed systemic lupus erythematosus.

PubMed

Yong, Jim Lc; Killingsworth, Murray C; Lai, Ken

2013-01-01

The pathological manifestations in the kidneys in systemic lupus erythematosus (SLE) are commonly known as lupus nephritis. We have studied the pathological changes in renal biopsies from 59 cases of clinically diagnosed SLE obtained over a 15-year period from a racially diverse population in the Sydney metropolitan area. Our aim was to see if there was any regional variation in the morphological changes. Renal biopsy changes were assessed by routine light, immunofluorescence, and electron microscopy. We used the modified 1974 World Health Organization classification of lupus nephritis to classify cases into six classes. Disease severity was assessed by age, sex, and across racial groups, including Caucasian, Asian, Middle Eastern, Mediterranean, Indian subcontinental, South American, and Pacific Islander. Our analysis showed that cases of lupus nephritis contributed 5.4% of our total renal biopsies examined over a 15-year period. The overall incidence of biopsy-proven cases was 0.49 per 100,000 per year. The ages of our patients ranged from 10 to 79 years, with most below 50 years of age. A female to male ratio was determined to be 4.4:1. There was no relationship to ethnicity, nor was there a relationship between any of these parameters and the class or severity of disease. Renal biopsy with multimodal morphological and immunohistochemical analysis remains the gold standard for diagnosis and determination of the level of disease in lupus nephritis. Based on this approach we have identified an incidence rate for southwest Sydney that is slightly higher but comparable to that found in a similar study from the United Kingdom. We also found that there was no relationship between sex, race, or age and severity of disease.

Control of lupus nephritis by changes of gut microbiota.

PubMed

Mu, Qinghui; Zhang, Husen; Liao, Xiaofeng; Lin, Kaisen; Liu, Hualan; Edwards, Michael R; Ahmed, S Ansar; Yuan, Ruoxi; Li, Liwu; Cecere, Thomas E; Branson, David B; Kirby, Jay L; Goswami, Poorna; Leeth, Caroline M; Read, Kaitlin A; Oestreich, Kenneth J; Vieson, Miranda D; Reilly, Christopher M; Luo, Xin M

2017-07-11

Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a "leaky" gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.

Renal biopsy pathology in a cohort of patients from southwest Sydney with clinically diagnosed systemic lupus erythematosus

PubMed Central

Yong, Jim LC; Killingsworth, Murray C; Lai, Ken

2013-01-01

Purpose The pathological manifestations in the kidneys in systemic lupus erythematosus (SLE) are commonly known as lupus nephritis. We have studied the pathological changes in renal biopsies from 59 cases of clinically diagnosed SLE obtained over a 15-year period from a racially diverse population in the Sydney metropolitan area. Our aim was to see if there was any regional variation in the morphological changes. Methods Renal biopsy changes were assessed by routine light, immunofluorescence, and electron microscopy. We used the modified 1974 World Health Organization classification of lupus nephritis to classify cases into six classes. Disease severity was assessed by age, sex, and across racial groups, including Caucasian, Asian, Middle Eastern, Mediterranean, Indian subcontinental, South American, and Pacific Islander. Results Our analysis showed that cases of lupus nephritis contributed 5.4% of our total renal biopsies examined over a 15-year period. The overall incidence of biopsy-proven cases was 0.49 per 100,000 per year. The ages of our patients ranged from 10 to 79 years, with most below 50 years of age. A female to male ratio was determined to be 4.4:1. There was no relationship to ethnicity, nor was there a relationship between any of these parameters and the class or severity of disease. Conclusion Renal biopsy with multimodal morphological and immunohistochemical analysis remains the gold standard for diagnosis and determination of the level of disease in lupus nephritis. Based on this approach we have identified an incidence rate for southwest Sydney that is slightly higher but comparable to that found in a similar study from the United Kingdom. We also found that there was no relationship between sex, race, or age and severity of disease. PMID:23431084

What is new in systemic lupus erythematosus.

PubMed

Rúa-Figueroa Fernández de Larrinoa, Iñigo

2015-01-01

Systemic lupus erythematosus is a heterogeneous rheumatic systemic disease with extremely varied clinical manifestations and a diverse pathogenesis, as illustrated in this review on the most relevant new knowledge related to the disease. Topics such as anemia, pathogenesis, cardiovascular risk assessment, antiphospholipid syndrome, prediction of damage and recent advances in treatment, including tolerogenic and biological agents, are discussed. Relevant contributions regarding classical therapies such as corticosteroid and antimalarials and their optimal use, as well as the roll of vitamin D, are also referred. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

One year in review 2016: systemic lupus erythematosus.

PubMed

Adinolfi, Antonella; Valentini, Eleonora; Calabresi, Emanuele; Tesei, Giulia; Signorini, Viola; Barsotti, Simone; Tani, Chiara

2016-01-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a highly variable course and prognosis. The management of the disease is still a clinical challenge for the treating physicians as many aspects regarding the disease pathogenesis, clinical picture and outcomes remain to be elucidated. New and interesting data are emerging; here the recent literature on SLE pathogenesis, clinical and laboratory aspects, as well as treatments and comorbidities, are reviewed and the main findings summarised in order to provide a bird's eye on the relevant papers on these topics.

Discoid lupus erythematosus treated with cryotherapy.

PubMed

Molin, L; Tarstedt, M

2003-09-01

A female is presented with multiple longstanding hypertrophic discoid lupus erythematosus lesions resistant to topical and systemic therapy for years. She suffered severe itching and pain localized to the lesions. Treatment with cryosurgery resulted in complete healing of the lesions, leaving slightly hypopigmented soft scars. There was no tendency of relapse during a follow-up period of ten years.

Computer simulation of vasectomy for wolf control

USGS Publications Warehouse

Haight, R.G.; Mech, L.D.

1997-01-01

Recovering gray wolf (Canis lupus) populations in the Lake Superior region of the United States are prompting state management agencies to consider strategies to control population growth. In addition to wolf removal, vasectomy has been proposed. To predict the population effects of different sterilization and removal strategies, we developed a simulation model of wolf dynamics using simple rules for demography and dispersal. Simulations suggested that the effects of vasectomy and removal in a disjunct population depend largely on the degree of annual immigration. With low immigration, periodic sterilization reduced pup production and resulted in lower rates of territory recolonization. Consequently, average pack size, number of packs, and population size were significantly less than those for an untreated population. Periodically removing a proportion of the population produced roughly the same trends as did sterilization; however, more than twice as many wolves had to be removed than sterilized. With high immigration, periodic sterilization reduced pup production but not territory recolonization and produced only moderate reductions in population size relative to an untreated population. Similar reductions in population size were obtained by periodically removing large numbers of wolves. Our analysis does not address the possible effects of vasectomy on larger wolf populations, but it suggests that the subject should be considered through modeling or field testing.

Frequency of dental caries in active and inactive systemic lupus erythematous patients: salivary and bacterial factors.

PubMed

Loyola Rodriguez, J P; Galvan Torres, L J; Martinez Martinez, R E; Abud Mendoza, C; Medina Solis, C E; Ramos Coronel, S; Garcia Cortes, J O; Domínguez Pérez, R A

2016-10-01

The objective of this study was to determine dental caries frequency and to analyze salivary and bacterial factors associated with active and inactive systemic lupus erythematous (SLE) patients. Also, a proposal to identify dental caries by a surface, teeth, and the patient was developed. A cross-sectional, blinded study that included 60 SLE patients divided into two groups of 30 subjects each, according to the Activity Index for Diagnosis of Systemic Lupus Erythematous (SLEDAI). The decayed, missing, and filled teeth (DMFT) index and Integrative Dental Caries Index (IDCI) were used for analyzing dental caries. The saliva variables recorded were: flow, pH, and buffer capacity. The DNA copies of Streptococcus mutans and Streptococcus sobrinus were estimated by real-time PCR. The caries frequency was 85% for SLE subjects (73.3% for inactive systemic lupus erythematous (ISLE) and 100% for active systemic lupus erythematous (ASLE)); DMFT for the SLE group was 12.6 ± 5.7 and the IDCI was (9.8 ± 5.9). The ASLE group showed a salivary flow of 0.65 compared with 0.97 ml/1 min from the ISLE group; all variables mentioned above showed a statistical difference (p < 0.05). The salivary pH was 4.6 (6.06 for ISLE and 3.9 for ASLE). The DNA copies of S. mutans and S. sobrinus were high; all variables mentioned above show a significant statistical difference (p < 0.05) between groups. SLE patients had high DMFT and IDCI scores that were associated with a decrease in salivary flow, pH, and buffer capacity. There were high counts of S. sobrinus and S. mutans species, and IDCI is a useful tool to provide more detail about dental caries in epidemiological studies. © The Author(s) 2016.

White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus.

PubMed

Cannerfelt, B; Nystedt, J; Jönsen, A; Lätt, J; van Westen, D; Lilja, A; Bengtsson, A; Nilsson, P; Mårtensson, J; Sundgren, P C

2018-06-01

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

Complement in Lupus Nephritis: New Perspectives.

PubMed

Bao, Lihua; Cunningham, Patrick N; Quigg, Richard J

2015-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical trials support the use of complement-targeted therapy in the treatment of SLE.

Langerhans Cells Maintain Local Tissue Tolerance in a Model of Systemic Autoimmune Disease1

PubMed Central

King, Jennifer K.; Philips, Rachael L.; Eriksson, Anna U.; Kim, Peter J.; Halder, Ramesh C.; Lee, Delphine J.; Singh, Ram Raj

2015-01-01

Systemic autoimmune diseases such as lupus affect multiple organs, usually in a diverse fashion where only certain organs are affected in individual patients. It is unclear whether the ‘local’ immune cells play a role in regulating tissue specificity in relation to disease heterogeneity in systemic autoimmune diseases. Here, we used skin as a model to determine the role of tissue-resident dendritic cells in local and systemic involvement within a systemic lupus disease model. Skin-resident dendritic cells, namely Langerhans cells (LC), have been implicated in regulating tolerance or autoimmunity using elegant transgenic models, however, their role in local versus systemic immune regulation is unknown. We demonstrate that while lymphocytes from skin-draining lymph nodes of autoimmune-prone MRL/MpJ-Faslpr/lpr mice react spontaneously to a physiological skin self-Ag desmoglein-3, epicutaneous applications of desmoglein-3 induced tolerance that is dependent on LCs. Inducible ablation of LCs in adult, preclinical MRL/MpJ-Faslpr/lpr and MRL/MpJ-Fas+/+ mice resulted in increased autoantibodies against skin Ags and markedly accelerated lupus dermatitis with increased local macrophage infiltration, but had no effect on systemic autoantibodies such as anti-dsDNA Abs or disease in other organs such as kidneys, lung, and liver. Furthermore, skin-draining lymph nodes of LC-ablated MRL/MpJ-Faslpr/lpr mice had significantly fewer CD4+ T-cells producing anti-inflammatory cytokine IL-10 than LC-intact controls. These results indicate that a skin-resident dendritic cell population regulates local tolerance in systemic lupus and emphasize the importance of the local immune milieu in preventing tissue-specific autoimmunity yet have no effect on systemic autoimmunity. PMID:26071559

High Prevalence of Personality Disorders in Skin-restricted Lupus Patients.

PubMed

Jalenques, Isabelle; Rondepierre, Fabien; Massoubre, Catherine; Bonnefond, Sophie; Schwan, Raymond; Labeille, Bruno; Perrot, Jean-Luc; Collange, Marianne; Mulliez, Aurelien; D'Incan, Michel

2017-08-31

Psychiatric and personality disorders have been extensively documented in patients with systemic lupus erythematosus (SLE). However, the prevalence of personality disorders in skin-restricted lupus (SRL) patients remains unknown. The aim of this study was to assess the prevalence of personality disorders in SRL outpatients and to examine the associated factors. We evaluated 60 SRL outpatients and 118 controls matched for sex, age and education level. On the basis of the Personality Diagnostic Questionnaire 4+, 38% of patients vs 20% of controls fulfilled the criteria for at least one personality disorder (OR 2.2 [95% CI 1.01-4.6], p = 0.048). Only one patient with a personality disorder had specialised mental health care. Late lupus onset and more frequent past treatments by thalidomide were associated factors. This study evidences a high prevalence of personality disorders in SRL patients and shows that most SRL patients with personality disorder do not receive specialised mental health care.

Monogenic Lupus.

PubMed

Lo, Mindy S

2016-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease known for its clinical heterogeneity. Over time, new insights into the complex genetic origin of SLE have started to explain some of this clinical variability. These findings, reviewed here, have also yielded important understanding in the immune mechanisms behind SLE pathogenesis. Several new monogenic disorders with lupus-like phenotype have been described. These can be organized into physiologic pathways that parallel mechanisms of disease in SLE. Examples include genes important for DNA damage repair (e.g., TREX1), nucleic acid sensing and type I interferon overproduction (e.g., STING, TREX1), apoptosis (FASLG), tolerance (PRKCD), and clearance of self-antigen (DNASE1L3). Further study of monogenic lupus may lead to better genotype/phenotype correlations in SLE. Eventually, the ability to understand individual patients according to their genetic profile may allow the development of more targeted and personalized approaches to therapy.

Protein-losing enteropathy associated with refractory systemic lupus erythematosus with a good response to rituximab.

PubMed

Sansinanea, Pierina; Carrica, Sebastián Augusto; Marcos, Josefina; García, Mercedes Argentina

2016-01-01

A case is presented of a protein-losing enteropathy (PLE) as the initial manifestation of systemic lupus erythematosus (SLE) in a 17 year-old female patient, who presented with ascites, edema and hypoalbuminemia. The diagnosis of SLE was based on the presence of: malar rash, oral ulcers, thrombocytopenia, antinuclear antibodies, IgM anticardiolipin antibody, and lupus anticoagulant. Renal and liver diseases were ruled out. The PLE diagnosis was confirmed with fecal alpha 1-antitrypsin clearance. The PLE was refractory to different lines of immunosuppressive agents like glucocorticoids, cyclophosphamide, azathioprine, and cyclosporine, showing a satisfactory and sustained response with rituximab, allowing steroid sparing and long term remission. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Drug-induced systemic lupus erythematosus in a child after 3 years of treatment with carbamazepine.

PubMed

Molina-Ruiz, Ana María; Lasanta, Begoña; Barcia, Ana; Pérez-Vega, Elisa; Requena, Luis

2017-02-01

Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50-70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few cases have been reported in children. We describe the case of CBZ-induced SLE in a 9-year-old girl following 3 years of CBZ therapy. This case report shows that drug-induced SLE is an important side-effect to be considered, even after long-term treatment with CBZ, and also during childhood. © 2015 The Australasian College of Dermatologists.

Peripheral blood lymphocyte response to phytomitogens in systemic lupus erythematosus

PubMed Central

Foad, B.; Adams, L. E.; Litwin, A.; Hess, E. V.

1976-01-01

Foad, B., Adams, L. E., Litwin, A., and Hess, E. V. (1976).Annals of the Rheumatic Diseases, 35, 407-414. Peripheral blood lymphocyte response to phytomitogens in systemic lupus erythematosus. The response of peripheral blood lymphocytes to the phytomitogens, PHA, Con A, and PWM, was evaluated in 30 SLE patients and in 30 age, sex, and race-matched controls using dose and time responses. The proliferative response to the three phytomitogens was not depressed in this group of subacute and chronic SLE patients. Active lupus nephritis and a slow acetylator phenotype were associated with a decreased lymphocyte response. The incidence of a slow acetylator phenotype in spontaneous SLE was 68%. In interpreting the lymphocyte response to phytomitogens, the importance of a clear definition of the SLE group under study, the activity of the disease, and treatment status are emphasized. PMID:1234408

Nailfold capillaroscopy in children and adolescents with rheumatic diseases.

PubMed

Piotto, Daniela Gerent Petry; Len, Cláudio Arnaldo; Hilário, Maria Odete Esteves; Terreri, Maria Teresa Ramos Ascensão

2012-10-01

To assess nailfold capillaroscopy in children and adolescents with autoimmune rheumatic diseases (juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis, scleroderma and mixed connective tissue disease) and relate it to clinical and laboratory findings and disease activity. Cross-sectional study assessing 147 patients by use of nailfold capillaroscopy as follows: 60 with juvenile idiopathic arthritis; 30 with systemic lupus erythematosus; 30 with juvenile dermatomyositis; 20 with localized scleroderma; four with systemic sclerosis; and three with mixed connective tissue disease. Clinical and laboratory tests and nailfold capillaroscopy were performed in all patients. The nailfold capillaroscopy was performed with an optical microscope (at 10- and 16-time magnifications) by the same observer. Most patients (76.2%) had normal nailfold capillaroscopy. The major changes in nailfold capillaroscopy, characterizing the scleroderma pattern, were observed in patients with juvenile dermatomyositis, systemic scleroderma and mixed connective tissue disease. There was no association between nailfold capillaroscopy and disease activity in patients with juvenile idiopathic arthritis, systemic lupus erythematosus and localized scleroderma. Disease activity and capillaroscopy were associated in patients with juvenile dermatomyositis. Nailfold capillaroscopy is a useful method to diagnose autoimmune rheumatic diseases and monitor disease activity.

Properties of skin stem cells and their potential clinical applications in modern dermatology.

PubMed

Niezgoda, Anna; Niezgoda, Piotr; Nowowiejska, Laura; Białecka, Agnieszka; Męcińska-Jundziłł, Kaja; Adamska, Urszula; Czajkowski, Rafał

2017-06-01

Stem cells play an important role in medical science, and scientists are investing large sums in order to perform sophisticated studies designed to establish potential clinical applications of stem cells. Growing experience has enabled researchers to determine the precise nature of stem cell division. Although the properties of this particular population of cells have been known and used for some time, mainly with regards to bone marrow-derived mesenchymal stem cell transplantation, we now face a significant challenge in implementing the practical use of skin-derived precursors, making it possible to avoid the necessity for patients to undergo invasive procedures in order to obtain stem cells from bone marrow. Multiple trials have so far been performed, bringing hope for the treatment of disorders previously considered untreatable. Patients suffering from a number of dermatological diseases, including malignant melanoma, systemic lupus erythematosus, vitiligo, alopecia or junctional epidermolysis bullosa, may benefit from treatment based on stem cells. The aim of this review is to summarize available data on stem cells and their potential applications in the treatment of dermatological disorders. The work described is based on data published up to the end of September 2016.

Normal and system lupus erythematosus red blood cell interactions studied by double trap optical tweezers: direct measurements of aggregation forces

NASA Astrophysics Data System (ADS)

Khokhlova, Maria D.; Lyubin, Eugeny V.; Zhdanov, Alexander G.; Rykova, Sophia Yu.; Sokolova, Irina A.; Fedyanin, Andrey A.

2012-02-01

Direct measurements of aggregation forces in piconewton range between two red blood cells in pair rouleau are performed under physiological conditions using double trap optical tweezers. Aggregation and disaggregation properties of healthy and pathologic (system lupus erythematosis) blood samples are analyzed. Strong difference in aggregation speed and behavior is revealed using the offered method which is proposed to be a promising tool for SLE monitoring at single cell level.

Dissecting the immune cell mayhem that drives lupus pathogenesis.

PubMed

Craft, Joseph E

2011-03-09

The autoimmune disease systemic lupus erythematosus (SLE) results from an inability of the immune system to discriminate between certain self-antigens and foreign ones. The most common treatment of SLE involves the use of immunosuppressive drugs to reduce inflammation, but these therapies have serious side effects. Three recent papers in Science Translational Medicine redirect focus on neutrophils, platelets, and interferon-α in the pathogenesis of SLE and reinforce the notion that researchers should seek to discover and devise combination therapies that target these processes.

Cat scratch disease in an immunosuppressed patient with systemic lupus erythematosus.

PubMed

Vargas-Hitos, J A; Sabio, J M; Navarrete-Navarrete, N; Arenas-Miras, M del M; Zamora-Pasadas, M; Jiménez-Alonso, J

2016-03-01

Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant. © The Author(s) 2015.

C5a alters blood-brain barrier integrity in experimental lupus

PubMed Central

Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G. N.; Quigg, Richard J.; Alexander, Jessy J.

2010-01-01

The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6lpr (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL+/+ mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases.—Jacob, A., Hack, B., Chiang, E., Garcia, J. G. N., Quigg, R. J., Alexander, J. J. C5a alters blood-brain barrier integrity in experimental lupus. PMID:20065106

Infodemiology of systemic lupus erythematous using Google Trends.

PubMed

Radin, M; Sciascia, S

2017-07-01

Objective People affected by chronic rheumatic conditions, such as systemic lupus erythematosus (SLE), frequently rely on the Internet and search engines to look for terms related to their disease and its possible causes, symptoms and treatments. 'Infodemiology' and 'infoveillance' are two recent terms created to describe a new developing approach for public health, based on Big Data monitoring and data mining. In this study, we aim to investigate trends of Internet research linked to SLE and symptoms associated with the disease, applying a Big Data monitoring approach. Methods We analysed the large amount of data generated by Google Trends, considering 'lupus', 'relapse' and 'fatigue' in a 10-year web-based research. Google Trends automatically normalized data for the overall number of searches, and presented them as relative search volumes, in order to compare variations of different search terms across regions and periods. The Menn-Kendall test was used to evaluate the overall seasonal trend of each search term and possible correlation between search terms. Results We observed a seasonality for Google search volumes for lupus-related terms. In the Northern hemisphere, relative search volumes for 'lupus' were correlated with 'relapse' (τ = 0.85; p = 0.019) and with fatigue (τ = 0.82; p = 0.003), whereas in the Southern hemisphere we observed a significant correlation between 'fatigue' and 'relapse' (τ = 0.85; p = 0.018). Similarly, a significant correlation between 'fatigue' and 'relapse' (τ = 0.70; p < 0.001) was seen also in the Northern hemisphere. Conclusion Despite the intrinsic limitations of this approach, Internet-acquired data might represent a real-time surveillance tool and an alert for healthcare systems in order to plan the most appropriate resources in specific moments with higher disease burden.

Current role of rituximab in systemic lupus erythematosus.

PubMed

Mok, Chi Chiu

2015-02-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by periods of flares and remission, resulting in organ damage over time caused by persistent disease activity and treatment-related complications. Conventional therapies are not ideal in terms of efficacy and safety. Novel biological therapies are being developed to enhance therapeutic efficacy, minimize disease exacerbation and reduce toxicities. As dysregulation of B cells is the hallmark of SLE, B-cell targeted therapies are the focus of recent clinical research. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been used with success in recalcitrant lupus manifestations. However, randomized controlled trials have failed to reveal its benefit in renal and non-renal SLE when combined with conventional immunosuppressive protocols. Although heterogeneity of SLE manifestations, pitfalls in study design and the limitations of the assessment tools for various clinical end points may have contributed to the discouraging results, rituximab remains an option in patients who are refractory or intolerant to conventional therapies. Recently, a regimen consisting of rituximab and mycophenolate mofetil without oral corticosteroids was reported to be effective in lupus nephritis. While the efficacy of this regimen has to be confirmed, future controlled trials should focus on the efficacy of rituximab in refractory lupus manifestations and its synergistic effect with other immunosuppressive agents such as cyclophosphamide. In short-term randomized controlled trials, a non-significant increase in serious adverse events was observed in SLE patients treated with rituximab. Long-term safety data of rituximab in SLE, in particular the incidence of hypogammaglobulinemia and serious/opportunistic infections, have to be continuously surveyed. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Molecular Basis of 9G4 B Cell Autoreactivity in Human Systemic Lupus Erythematosus

PubMed Central

Richardson, Christopher; Chida, Asiya Seema; Adlowitz, Diana; Silver, Lin; Fox, Erin; Jenks, Scott A.; Palmer, Elise; Wang, Youliang; Heimburg-Molinaro, Jamie; Li, Quan-Zhen; Mohan, Chandra; Cummings, Richard; Tipton, Christopher

2013-01-01

9G4+ IgG Abs expand in systemic lupus erythematosus (SLE) in a disease-specific fashion and react with different lupus Ags including B cell Ags and apoptotic cells. Their shared use of VH4-34 represents a unique system to understand the molecular basis of lupus autoreactivity. In this study, a large panel of recombinant 9G4+ mAbs from single naive and memory cells was generated and tested against B cells, apoptotic cells, and other Ags. Mutagenesis eliminated the framework-1 hydrophobic patch (HP) responsible for the 9G4 idiotype. The expression of the HP in unselected VH4-34 cells was assessed by deep sequencing. We found that 9G4 Abs recognize several Ags following two distinct structural patterns. B cell binding is dependent on the HP, whereas anti-nuclear Abs, apoptotic cells, and dsDNA binding are HP independent and correlate with positively charged H chain third CDR. The majority of mutated VH4-34 memory cells retain the HP, thereby suggesting selection by Ags that require this germline structure. Our findings show that the germline-encoded HP is compulsory for the anti–B cell reactivity largely associated with 9G4 Abs in SLE but is not required for reactivity against apoptotic cells, dsDNA, chromatin, anti-nuclear Abs, or cardiolipin. Given that the lupus memory compartment contains a majority of HP+ VH4-34 cells but decreased B cell reactivity, additional HP-dependent Ags must participate in the selection of this compartment. This study represents the first analysis, to our knowledge, of VH-restricted autoreactive B cells specifically expanded in SLE and provides the foundation to understand the antigenic forces at play in this disease. PMID:24108696

[Kikuchi-Fujimoto disease prior to childhood-systemic lupus erythematosus diagnosis].

PubMed

Martins, Sofia S; Buscatti, Izabel M; Freire, Pricilla S; Cavalcante, Erica G; Sallum, Adriana M; Campos, Lucia M A; Silva, Clovis A

2014-01-01

Kikuchi-Fujimoto disease (KFD) is a self-limiting histiocytic necrotizing lymphadenitis of unknown origin. Of note, KFD was infrequently reported in adult systemic lupus erythematosus (SLE), with rare occurrence in childhood-SLE (C-SLE) patients. To our knowledge, the prevalence of KFD in the paediatric lupus population was not studied. Therefore, in a period of 29 consecutive years, 5,682 patients were followed at our institution and 289 (5%) met the American College of Rheumatology classification criteria for SLE, one had isolated KFD (0.03) and only one had KFD associated to C-SLE diagnoses, which case was reported herein. A 12 year-old female patient had high fever, fatigue and cervical and axillary lymphadenopathy. The antinuclear antibodies (ANA) were negative, with positive IgM and IgG herpes simplex virus type 1 and type 2 serologies. Fluorine-18-fluoro-deoxy-glucose positron emission tomography/computed tomography (PET/CT) imaging demonstrated diffuse lymphadenopathy. The axillary lymph node biopsy showed necrotizing lymphadenitis with histiocytes, without lymphoproliferative disease, compatible with KFD. After 30 days, she presented spontaneous regression and no therapy was required. Nine months later, she developed malar rash, photosensitivity, oral ulcers, lymphopenia and ANA 1:320 (homogeneous nuclear pattern). At that moment the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 and she was treated with prednisone (1.0mg/kg/day) and hidroxychloroquine showing progressive improvement of hers signs and symptoms. In conclusion, KFD is a benign and rare disease in our paediatric lupus population. We also would like to reinforce the relevance of autoimmune diseases diagnosis during the follow-up of patients with KFD. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Lupus Band Test in Patients with Borderline Systemic Lupus Erythematosus with Discoid Lesions.

PubMed

Akarsu, Sevgi; Ozbagcivan, Ozlem; Ilknur, Turna; Semiz, Fatma; Lebe, Banu; Fetil, Emel

2017-04-01

Patients with lupus erythematosus (LE) that have discoid lesions who fulfill the four diagnostic criteria of systemic lupus erythematosus (SLE) with only mucocutaneous findings and antinuclear antibody (ANA) positivity were classified as borderline SLE in the literature. Objective of this study was to determine the place of borderline SLE with discoid lesions on the LE spectrum according to the lupus band test (LBT). Lesional and sun-protected non-lesional (SPNL) skin LBTs of 94 patients with LE that had discoid lesions were retrospectively evaluated. Firstly, patients were divided into two main groups: discoid LE (DLE; group A) and SLE (Group B); three subgroups were then classified as DLE (Group A), borderline SLE (Group B1) and SLE (Group B2) using another method. Each group had its own comparisons. Immunoreactant (IR) deposition was observed on the lesional skin in all patients and on the SPNL skin in 42 (44.7%). In patients with borderline SLE, the deposition of IgM was lower on the lesional LBTs, whereas isolated IgG was higher than SLE; thus, it shows similarity with DLE. Additionally, it was also closer to DLE because of the low deposition of C3, multiple IRs, and a double conjugate of IRs on the SPNL skin. However, it showed similarity with SLE in the high percentage of LBT positivity and more immunoglobulin M (IgM) and immunoglobulin G (IgG) deposition on the SPNL skin. The deposition of multiple conjugates on SPNL skin in patients with LE with discoid lesions may reflect systemic involvement. Despite the fact that LBT positivity on SPNL skin in borderline SLE was higher than DLE, less deposition of multiple conjugates compared to SLE indicates that the classification of borderline SLE with discoid lesions in the LE spectrum is questionable.

Associations of the Levels of C4d-bearing Reticulocytes and High-avidity Anti-dsDNA Antibodies with Disease Activity in Systemic Lupus Erythematosus.

PubMed

Mora, Claudia; Medina-Rosas, Jorge; Santos, Ana Maria; Jaimes, Diego A; Arbeláez, Ana M; Romero, Consuelo; Cortes, Annie; Londono, John

2016-09-01

There are no laboratory tools that detect early flares in systemic lupus erythematosus (SLE). Our aim was to validate in our population the previous findings of the association of C4d-bearing reticulocytes (R-C4d) compared to anti-dsDNA antibodies, with disease activity assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) 2004 scales. All patients who met the 1987 American College of Rheumatology classification criteria and were seen consecutively in 2013 at a specialized SLE care clinic were included. Disease activity was established by the SELENA-SLEDAI and BILAG 2004. Anti-dsDNA and R-C4d were quantified in peripheral blood. Comparisons were made between values of active and inactive patients, and the correlations between the SELENA-SLEDAI and serum levels of anti-dsDNA and R-C4d were measured. Sixty-two patients (83.9% women) were included. A total of 32.3% had active disease according to the SELENA-SLEDAI. There was a significant statistical difference (p = 0.0001) in the distribution of R-C4d between disease activity groups. The correlation coefficient between R-C4d and the SELENA-SLEDAI score was rs = 0.738 (p = 0.0001). R-C4d differed between patients with and without activity in the BILAG 2004 constitutional, mucocutaneous, gastrointestinal, renal, and hematological domains. R-C4d showed a higher correlation with SLE activity measured by the SELENA-SLEDAI and BILAG 2004 than anti-dsDNA did, suggesting a possible involvement in diagnosing disease activity. Prospective studies that confirm these findings and evaluate its involvement in followup are needed.

Systemic lupus erythematosus-associated neutrophilic dermatosis--an underrecognized neutrophilic dermatosis in patients with systemic lupus erythematosus.

PubMed

Larson, Allison R; Granter, Scott R

2014-03-01

Neutrophilic dermatoses are an uncommon manifestation of lupus. We describe the clinical and histopathologic features of 14 patients with systemic lupus erythematosus (SLE) and neutrophilic dermatoses, 2 of whom had no prior history of SLE. Thirteen patients were female, ranging in age from 27 to 62 years (mean age, 42.8 years). One patient was a 20-year-old man. Most lesions were described as erythematous papules and plaques and showed annular morphology in 6 patients and a photodistribution in 2 patients. Histopathologic examination in all cases showed an interstitial neutrophilic infiltrate with leukocytoclasis that ranged from sparse in 5 cases and moderate to dense in 9 cases. With one exception, those cases with moderate to dense infiltrates resembled Sweet's syndrome at scanning magnification. Two cases resembled bullous SLE, and 1 case showed overlapping features of bullous SLE and Sweet's syndrome. Interface changes were seen in 8 patients, which were subtle and vacuolar in 7. One case was associated with a florid interface tissue reaction. Dermal mucin was seen in 4 cases and was a prominent feature in only one of these. One case showed a minute discrete focus resembling palisaded neutrophilic and granulomatous dermatitis. It is important to consider SLE-associated neutrophilic dermatosis in the differential diagnosis of neutrophilic tissue reactions particularly because some patients will have no prior history of lupus. It is also important to be aware of the broad histologic spectrum that may be encountered in SLE-associated neutrophilic dermatosis, ranging from subtle paucicellular lesions to florid Sweet's-like lesions associated with a dense neutrophilic infiltrate. Copyright © 2014 Elsevier Inc. All rights reserved.

Differences in the diagnosis and management of systemic lupus erythematosus by primary care and specialist providers in the American Indian/Alaska Native population.

PubMed

McDougall, J A; Helmick, C G; Lim, S S; Johnston, J M; Gaddy, J R; Gordon, C; Ferucci, E D

2018-06-01

Objectives The objective of this study is to investigate differences in the diagnosis and management of systemic lupus erythematosus (SLE) by primary care and specialist physicians in a population-based registry. Methods This study includes individuals from the 2009 Indian Health Service lupus registry population with a diagnosis of SLE documented by either a primary care provider or specialist. SLE classification criteria, laboratory testing, and medication use at any time during the course of disease were determined by medical record abstraction. Results Of the 320 individuals with a diagnosis of SLE, 249 had the diagnosis documented by a specialist, with 71 documented by primary care. Individuals with a specialist diagnosis of SLE were more likely to have medical record documentation of meeting criteria for SLE by all criteria sets (American College of Rheumatology, 79% vs 22%; Boston Weighted, 82% vs 32%; and Systemic Lupus International Collaborating Clinics, 83% vs 35%; p < 0.001 for all comparisons). In addition, specialist diagnosis was associated with documentation of ever having been tested for anti-double-stranded DNA antibody and complement 3 and complement 4 ( p < 0.001). Documentation of ever receiving hydroxychloroquine was also more common with specialist diagnosis (86% vs 64%, p < 0.001). Conclusions Within the population studied, specialist diagnosis of SLE was associated with a higher likelihood of having SLE classification criteria documented, being tested for biomarkers of disease, and ever receiving treatment with hydroxychloroquine. These data support efforts both to increase specialist access for patients with suspected SLE and to provide lupus education to primary care providers.

A quality-of-life study of cutaneous lupus erythematosus.

PubMed

Batalla, A; García-Doval, I; Peón, G; de la Torre, C

2013-11-01

The study of quality of life in patients with skin disorders has become more important in recent decades. In the case of lupus erythematosus, most quality-of-life studies have focused on the systemic form of the disease, with less attention being paid to the cutaneous form. The main objective of this study was to evaluate quality of life in patients with cutaneous lupus erythematosus (CLE) using a dermatology-specific questionnaire: the Dermatology Life Quality Index (DLQI). Our secondary objective was to investigate associations between DLQI scores and other aspects of the disease. Thirty-six patients with CLE completed the DLQI questionnaire. Other factors assessed were disease severity (measured using the Cutaneous Lupus Erythematosus Disease Area and Severity Index), time since diagnosis, body surface area affected, previous and current treatments, and the presence of criteria for systemic lupus erythematosus (SLE). According to the DLQI, CLE had a moderate, very large, or extremely large effect on quality of life in 50% of the patients analyzed (18/36). No significant associations were found between DLQI scores and disease severity, time since diagnosis, body surface area affected, number, type, or duration of pharmacologic treatments, or the presence or absence of SLE criteria. CLE has a significant and lasting effect on patient quality of life. This effect is probably primarily due to multiple factors, including the chronic nature of the disease, the visibility of the lesions, and the fact that they can cause disfigurement. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Immunosuppressive Effect of B7-H4 Pathway in a Murine Systemic Lupus Erythematosus Model.

PubMed

Xiao, Ze Xiu; Zheng, Xu; Hu, Li; Wang, Julie; Olsen, Nancy; Zheng, Song Guo

2017-01-01

B7-H4, one of the co-stimulatory molecules of the B7 family, has been shown to play an important role in negatively regulating the adaptive immune response by inhibiting the proliferation, activation, and cytokine production of T cells. In this study, we investigate the role of B7-H4 in development of systemic lupus erythematosus (SLE). We investigated a murine model of SLE using transfer of bone marrow-derived dendritic cells (BMDCs) that were incubated with activated syngeneic lymphocyte-derived DNA. The recipient mouse produced anti-ds-DNA antibodies as well as displayed splenomegaly and lymphadenopathy as shown by significantly increased weights, and the kidneys showed lupus-like pathological changes include urine protein and glomerulonephritis with hyperplasia in glomeruli and increased mesangial cells and vasculitis with perivascular cell infiltration, glomerular deposition of IgG and complement C3. We showed that B7-H4 deficiency in BMDCs could cause greater production of anti-ds-DNA antibodies in transferred mice, and the lymph tissue swelling and the kidney lesions were also exacerbated with B7-H4 deficiency. Treatment with a B7-H4 antagonist antibody also aggravated the lupus model. Conversely, B7-H4 Ig alleviated the lupus manifestations. Therefore, we conclude that B7-H4 is a negative check point for the development of SLE in this murine model. These results suggest that this approach may have a clinical potential in treating human SLE.

Immunosuppressive Effect of B7-H4 Pathway in a Murine Systemic Lupus Erythematosus Model

PubMed Central

Xiao, Ze Xiu; Zheng, Xu; Hu, Li; Wang, Julie; Olsen, Nancy; Zheng, Song Guo

2017-01-01

B7-H4, one of the co-stimulatory molecules of the B7 family, has been shown to play an important role in negatively regulating the adaptive immune response by inhibiting the proliferation, activation, and cytokine production of T cells. In this study, we investigate the role of B7-H4 in development of systemic lupus erythematosus (SLE). We investigated a murine model of SLE using transfer of bone marrow-derived dendritic cells (BMDCs) that were incubated with activated syngeneic lymphocyte-derived DNA. The recipient mouse produced anti-ds-DNA antibodies as well as displayed splenomegaly and lymphadenopathy as shown by significantly increased weights, and the kidneys showed lupus-like pathological changes include urine protein and glomerulonephritis with hyperplasia in glomeruli and increased mesangial cells and vasculitis with perivascular cell infiltration, glomerular deposition of IgG and complement C3. We showed that B7-H4 deficiency in BMDCs could cause greater production of anti-ds-DNA antibodies in transferred mice, and the lymph tissue swelling and the kidney lesions were also exacerbated with B7-H4 deficiency. Treatment with a B7-H4 antagonist antibody also aggravated the lupus model. Conversely, B7-H4 Ig alleviated the lupus manifestations. Therefore, we conclude that B7-H4 is a negative check point for the development of SLE in this murine model. These results suggest that this approach may have a clinical potential in treating human SLE. PMID:29321778

Severe Tissue Trauma Triggers the Autoimmune State Systemic Lupus Erythematosus in the MRL/++ Lupus-Prone Mouse

DTIC Science & Technology

2009-01-01

to a trans- planted ’self skin (isograft). We transplanted synge- neic naive skin onto the dorsum of MRL/++ mice 30-40 days post-bum injury. Graft...through molecular mimicry . Nat Med 2005; 11: 85-89. Cooper GS, Dooley MA, Treadwell EL, St Clair EW, Gilkeson GS. Risk factors for development of

Acute diffuse alveolar haemorrhage accompanied by gastrointestinal bleeding in a patient with serious systemic lupus erythematosus: A case report.

PubMed

Du, Jing; Wang, Ying; Li, Yan-Chun; Wang, Tong-Tong; Zhou, Yong-Lie; Ying, Zhen-Hua

2018-05-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organs, but multisystem dysfunction is rare. Here, we report a case of a 29-year-old woman who was initially diagnosed with SLE complications including lupus nephritis, lupus encephalopathy, renal hypertension, thrombocytopenia, anaemia and hyperkalaemia. She recovered following treatment with high dose methylprednisolone, intravenous immunoglobulin (IVIG) and continuous renal replacement therapy (CRRT). However, a few days after hospital discharge, she developed gastrointestinal bleeding. Although intensive treatment was administered, the patient deteriorated rapidly and had a progressive decline in oxygen saturation followed by diffuse alveolar haemorrhage and acute left heart failure. Inotropic therapy, mechanical ventilation, blood transfusion, CRRT, antibiotics, intravenous glucocorticoids and other support therapies were initiated and gradually the patient's vital signs stabilized and haemoptysis subsided. This case report emphasises that complications of SLE can occur at any stage of the disease, especially in patients with active SLE. Therefore, it is important for clinicians to be aware of the rare presentations of SLE and its complex management. For multisystem dysfunction, early intensive treatment with high dose corticosteroids and cyclophosphamide is advocated.

CD11b activation suppresses TLR-dependent inflammation and autoimmunity in systemic lupus erythematosus

PubMed Central

Faridi, Mohd Hafeez; Khan, Samia Q.; Zhao, Wenpu; Lee, Ha Won; Altintas, Mehmet M.; Zhang, Kun; Kumar, Vinay; Armstrong, Andrew R.; Carmona-Rivera, Carmelo; Dorschner, Jessica M.; Schnaith, Abigail M.; Li, Xiaobo; Ghodke-Puranik, Yogita; Moore, Erica; Irizarry-Caro, Jorge; Zhang, Tingting; Day, Rachael; Stoub, Darren; Hoffmann, Victoria; Khaliqdina, Shehryar Jehangir; Bhargava, Prachal; Santander, Ana M.; Torroella-Kouri, Marta; Issac, Biju; Cimbaluk, David J.; Zloza, Andrew; Prabhakar, Rajeev; Deep, Shashank; Jolly, Meenakshi; Koh, Kwi Hye; Reichner, Jonathan S.; Bradshaw, Elizabeth M.; Chen, JianFeng; Moita, Luis F.; Yuen, Peter S.; Li Tsai, Wanxia; Singh, Bhupinder; Reiser, Jochen; Nath, Swapan K.; Niewold, Timothy B.; Vazquez-Padron, Roberto I.

2017-01-01

Genetic variations in the ITGAM gene (encoding CD11b) strongly associate with risk for systemic lupus erythematosus (SLE). Here we have shown that 3 nonsynonymous ITGAM variants that produce defective CD11b associate with elevated levels of type I interferon (IFN-I) in lupus, suggesting a direct link between reduced CD11b activity and the chronically increased inflammatory status in patients. Treatment with the small-molecule CD11b agonist LA1 led to partial integrin activation, reduced IFN-I responses in WT but not CD11b-deficient mice, and protected lupus-prone MRL/Lpr mice from end-organ injury. CD11b activation reduced TLR-dependent proinflammatory signaling in leukocytes and suppressed IFN-I signaling via an AKT/FOXO3/IFN regulatory factor 3/7 pathway. TLR-stimulated macrophages from CD11B SNP carriers showed increased basal expression of IFN regulatory factor 7 (IRF7) and IFN-β, as well as increased nuclear exclusion of FOXO3, which was suppressed by LA1-dependent activation of CD11b. This suggests that pharmacologic activation of CD11b could be a potential mechanism for developing SLE therapeutics. PMID:28263189

Asymptomatic diffuse "encephalitic" cerebral toxoplasmosis in a woman with systemic lupus erythematosus.

PubMed

Murro, Diana; Novo, Jorge; Arvanitis, Leonidas

2016-07-01

Classic cerebral toxoplasmosis typically presents with neurologic symptoms such as seizures and mental status changes and histological examination shows focal lesions with necrosis. However, in the diffuse "encephalitic" form, patients are asymptomatic with diffuse, inflammatory, non-necrotic lesions. Asymptomatic diffuse "encephalitic" toxoplasmosis has been reported only in four acquired immunodeficiency syndrome patients and one human immunodeficiency virus (HIV) negative patient with chronic lymphocytic leukemia. We present a 36-year-old HIV-negative woman with systemic lupus erythematosus and lupus nephritis who was on immunosuppression for 9years after cadaveric renal transplant and died from pulmonary hemorrhage and cytomegalovirus pneumonia. Brain autopsy findings revealed multifocal microglial nodules containing Toxoplasma bradyzoites and associated astrogliosis. These nodules were prominent in the cerebellum, midbrain and medulla and also present in the cortex and thalamus. No coagulative necrosis, necrotizing abscesses, or other opportunistic infections were present. The patient had previously exhibited no neurologic symptoms and there was no clinical suspicion for toxoplasmosis. To the best of our knowledge, this is the first case of diffuse, non-necrotizing, "encephalitic" cerebral toxoplasmosis reported in a lupus patient and also the first reported female case. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pregnancy in women with systemic lupus erythematosus.

PubMed

Kiss, Emese; Bhattoa, Harjit P; Bettembuk, Peter; Balogh, Adam; Szegedi, Gyula

2002-03-10

Systemic lupus erythematosus (SLE) is an autoimmune disorder which may be affected by hormonal changes, such as those of pregnancy. Women with SLE have increased adverse pregnancy outcomes. A retrospective analysis of the gynecologic and immunologic case history of 140 women with SLE and the outcome of 263 pregnancies in 99 women with SLE. In patients diagnosed with SLE, the proportion of pregnancies ending with live birth at term decreased to one-third compared with three quarters in those without a diagnosis of SLE and the incidence of pre-term deliveries and spontaneous abortions increased by 6.8 and 4.7 times, respectively. When SLE was associated with secondary antiphospholipid (APL) syndrome, and lupus anticoagulant (LA) or beta2-glycoprotein antibodies were present, a further increase in the incidence of pregnancy loss was observed. Pregnancy did not cause a flare-up of SLE in all cases, the disease remained stable in about 30% of the patients. Lupus was mild in the majority of the women who carried out their pregnancy to term. We also observed mothers with active SLE who successfully carried out pregnancies to term. These findings accord with previous literature and should inform rheumatologists, obstetricians and neonatologists who guide patients in their reproductive decisions.

Aggressive periodontitis in a patient with chronic cutaneous lupus erythematosus: a case report.

PubMed

Tietmann, Christina; Bissada, Nabil F

2006-05-01

Lupus erythematosus is considered to be a high risk factor for periodontitis. As an autoimmune disease of unknown origin, cutaneous lupus erythematosus (CLE) is subdivided into 3 categories: chronic (CCLE), subacute (SCLE), and acute (ACLE). While the ACLE has a high prevalence of conjunctive periodontal lesions, aggressive periodontitis in patients with CCLE has been rarely reported. This article describes the case of a patient diagnosed with aggressive periodontitis. Three months after the diagnosis of periodontitis, the patient experienced advancing hair loss (alopecia), pale fingers and toes, as well as edema in the legs and around the eyes. Skin biopsy showed follicular hyperkeratosis with perivascular mononuclear cell infiltrate. Colliquation of the basal cells, thickening of the basal lamina, and vacuolar degeneration of basal keratinocytes were also found. A lupus band test was positive, and diagnosis of CCLE was established. Three months following the treatment of lupus with antimalarial agents, the periodontal condition became stable with no further exacerbation or progression of the existing periodontitis. An 11-month postsurgical follow-up revealed stable periodontal and general medical conditions. A patient's medical history should be re-evaluated in the event of recurrence of periodontal lesions refractory to periodontal treatment. The control of systemic conditions like lupus erythematosus is essential for a good prognosis in the treatment of periodontitis as well as for the general health of the patient.

Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis.

PubMed

Mota, Pedro; Reddy, Venkat; Isenberg, David

2017-07-01

Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.

Protein-losing enteropathy as initial manifestation of systemic lupus erythematosus.

PubMed

Carneiro, F O A A; Sampaio, L R; Brandão, L A R; Braga, L L B C; Rocha, F A C

2012-04-01

Protein-losing enteropathy is a rare manifestation of systemic lupus erythematosus. We report the case of an 18-year-old woman that presented initially with diarrhoea and anasarca. During evaluation, there was low serum albumin of 1.6 g/dl (3.5-5.2 g/dl) and a positive antinuclear antibody test (1:2560). Anti-Sm antibodies (ELISA) were positive in addition to low serum C3 of 35 mg/dl. A scintigraphy using 99mTc-labelled albumin was positive for abdominal protein loss. A diagnosis of systemic lupus erythematosus related protein-losing enteropathy was made. She was started on prednisolone 40 mg/day without amelioration; a month later, azathioprine (100 mg/day) was added, leading to normalization of serum albumin and resolution of symptoms within 4 months. After 1.5 years, the patient developed a 2.9 g 24-h proteinuria while still in remission of the protein-losing enteropathy, receiving 5 mg prednisone and 100 mg azathioprine daily.