Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of autoimmune diseases is still not clear but genetic, immunological, hormonal and environmental factors are considered to be important triggers. Most often autoimmunity is not followed by clinical symptoms unless an additional event such as an environmental factor favors an overt expression. Many environmental factors are known to affect the immune system and may play a role as triggers of the autoimmune mosaic.Infections: bacterial, viral and parasitic infections are known to induce and exacerbate autoimmune diseases, mainly by the mechanism of molecular mimicry. This was studied for some syndromes as for the association between SLE and EBV infection, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and more. Vaccines, in several reports were found to be temporally followed by a new onset of autoimmune diseases. The same mechanisms that act in infectious invasion of the host, apply equally to the host response to vaccination. It has been accepted for diphtheria and tetanus toxoid, polio and measles vaccines and GBS. Also this theory has been accepted for MMR vaccination and development of autoimmune thrombocytopenia, MS has been associated with HBV vaccination. Occupational and other chemical exposures are considered as triggers for autoimmunity. A debate still exists about the role of silicone implants in induction of scleroderma like disease.Not only foreign chemicals and agents have been associated with induction of autoimmunity, but also an intrinsic hormonal exposure, such as estrogens. This might explain the sexual dimorphism in autoimmunity.Better understanding of these environmental risk factors will likely lead to explanation of the mechanisms of onset and progression of autoimmune diseases and may lead to effective preventive involvement in specific high-risk groups. So by diagnosing a new patient with autoimmune disease a wide anamnesis work should be done.
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PMID:Infection, vaccines and other environmental triggers of autoimmunity. 1612 12

Infection is the major complication of cyclophosphamide therapy in patients with lupus nephritis. The objectives of this study were to report and compare the rate of infection between children with lupus nephritis who had received intravenous pulse cyclophosphamide (IVCY) and those who had received oral cyclophosphamide (OCY) and to determine the risk factors for infection during treatment with cyclophosphamide in these groups. Records of nine patients who had received IVCY from the beginning [pure intravenous cyclophosphamide (PIVCY) group], 11 patients who had received prior oral cyclophosphamide and later switched to IVCY [combined intravenous cyclophosphamide (CIVCY) group] and 41 patients who had received OCY were reviewed. Infection occurred in 21 of 61 patients (34%). In the PIVCY group, four episodes of infection occurred in three of nine patients (33%). In the CIVCY group, six episodes of infection occurred in four of 11 patients (36%). In the OCY group, 18 episodes of infection occurred in 14 of 41 patients (34%). The rate of infection between these groups was not different (P=0.99). None of the following parameters were risk factors for infection: cumulative dose of cyclophosphamide, leukopenia and neutropenia. On the contrary, white blood cell (WBC) count and polymorphonuclear cell (PMN) count were significantly less in the no-infection group (P=<0.001, P<0.001, respectively), with odds ratios for leukopenia (WBCs <4,000 mm(3)) and neutropenia (PMNs <1,500 mm(3)) between the infection and the no-infection group equal to 0.18 (95%CI 0.05-0.63) and 0 (95%CI 0-0.19), respectively. Most of the patients who had infection received prednisolone at a dosage of more than 0.5 mg/kg per day (67% of the PIVCY group, 50% of the CIVCY group and 83% of the OCY group). Fatal infections occurred in two patients who had concomitant active systemic lupus erythematosus (SLE). Although lymphopenia (lymphocyte count <1,500/mm(3)) was not the risk factor for infection, it was observed that six of seven patients with herpes zoster had lymphopenia. Herpes zoster seemed to occur more frequently in the OCY group (15%) than in the whole IVCY group (5%), but there was no statistical difference (P=0.41). We conclude that the rate of infection in the IVCY and OCY group was not different. Infection is likely to occur in patients receiving a concomitant high dose of prednisolone. The occurrence of fatal infection in patients with active disease should be noted. No single risk factor was detected in this study.
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PMID:Infection in children with lupus nephritis receiving pulse and oral cyclophosphamide therapy. 1613 37

Viral and bacterial infections may serve as an environmental trigger for the development or exacerbation of systemic lupus erythematosus (SLE) in the genetically predetermined individual. In addition, SLE patients are more prone to develop common (pneumonia, urinary tract infection, cellulitis, sepsis), chronic (tuberculosis), and opportunistic infections possibly due to inherit genetic and immunologic defects (complement deficiencies, mannose-binding lectin [MBL] polymorphisms, elevated Fcgamma III and GM-CSF levels, osteopontion polymorphism), but also due to the broad spectrum immunosuppressive agents that are part of therapy for severe manifestations of the disease. Hence, SLE patients are considered a high-risk population, where identification and treatment of chronic infections such as tuberculosis, hepatitis B or human immunodeficiency virus, are important prior to the institution of immunosuppression so as to prevent reactivation or exacerbation of the infection. Infections in SLE patients remain a source of morbidity and mortality. A caveat often encountered is to distinguish between a lupus flare and an acute infection; in such cases parameters including elevated CRP (and adhesion molecules) may aid in the diagnosis of infection. Recent research has provided convincing evidence that EBV infection may play a major role not only in molecular mimicry but also in aberrations of B cells and apoptosis leading to a state of perpetual heightened immune response in SLE.
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PMID:Infections and SLE. 1637 52

Systemic lupus erythematosus (SLE or lupus) is a complex disease with a multifactoral etiology, with genetic, hormonal, and environmental influences. Molecular mimicry as a result of viral infection may contribute to the development of lupus. The pattern of autoantibody development in lupus is consistent with initiation through molecular mimicry, as the initial autoantigenic epitopes that have been observed are limited and cross-reactive with viral proteins. Autoantibody specificity may then later diversify to other autoantigens through B-cell epitope spreading. Epstein-Barr virus (EBV) is an excellent candidate to be involved in molecular mimicry in lupus. EBV infection has been associated with lupus through serological and DNA studies. Infection with EBV results in the production of the viral protein Epstein-Barr virus nuclear antigen-1 (EBNA-1), antibodies against which cross-react with lupus-associated autoantigens, including Ro, Sm B/B', and Sm D1, in lupus patients. The immune response against EBV, and EBNA-1 in particular, differs among lupus patients and healthy controls, with controls maintaining a limited humoral response and failing to produce long-standing cross-reactive antibodies. We hypothesize that the humoral immune response to EBNA-1 in susceptible individuals leads to the generation of cross-reactive antibodies. Through the process of epitope spreading, these cross-reactive antibodies target additional, non-cross reactive autoepitopes, spread to additional autoantigens, and become pathogenic, leading eventually to clinical lupus. This paper reviews some of the current literature supporting roles for EBV exposure and epitope spreading in SLE.
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PMID:Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus. 1645 83

Infection imposes a serious burden on patients with systemic lupus erythematosus (SLE). The increased infection rate in SLE patients has been attributed in part to defects of immune defence. Recently, the lectin pathway of complement activation has also been suggested to play a role in the occurrence of infections in SLE. In previous studies, SLE patients homozygous for mannose-binding lectin (MBL) variant alleles were at an increased risk of acquiring serious infections in comparison with patients who were heterozygous or homozygous for the normal allele. This association suggests a correlation between functional MBL level and occurrence of infections in SLE patients. We therefore investigated the biological activity of MBL and its relationship with the occurrence of infections in patients with SLE. Demographic and clinical data were collected in 103 patients with SLE. Functional MBL serum levels and MBL-induced C4 deposition were measured by enzyme-linked immunosorbent assay using mannan as coat and an MBL- or C4b-specific monoclonal antibody. The complete MBL-dependent pathway activity was determined by using an assay that measures the complete MBL pathway activity in serum, starting with binding of MBL to mannan, and was detected with a specific monoclonal antibody against C5b-9. Charts were systematically reviewed to obtain information on documented infections since diagnosis of SLE. Major infections were defined as infections requiring hospital admission and intravenous administration of antibiotics. In total, 115 infections since diagnosis of lupus, including 42 major infections, were documented in the 103 SLE patients (mean age 41 +/- 13 years, mean disease duration 7 +/- 4 years). The percentage of SLE patients with severe MBL deficiency was similar to that in 100 healthy controls: 13% versus 14%, respectively. Although deposition of C4 to mannan and MBL pathway activity were reduced in 21% and 43% of 103 SLE patients, respectively, neither functional MBL serum levels nor MBL pathway activity was associated with infections or major infections in regression analyses. In conclusion, SLE patients frequently suffer from infections, but deficiency of functional MBL does not confer additional risk.
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PMID:Deficiency of functional mannose-binding lectin is not associated with infections in patients with systemic lupus erythematosus. 1716 54

The catastrophic anti-phospholipid syndrome (CAPS) differs from the anti-phospholipid syndrome in its accelerated systemic involvement leading to multi-organic failure. In this study, the occurrence of malignancies in patients with CAPS was evaluated and the clinical findings of CAPS patients with and without malignancies were compared. We investigated the web site-based international registry of patients with CAPS for all cases in which both CAPS and underlying malignancies were present. The clinical characteristics of these cases were subsequently evaluated to establish common characteristics. The CAPS registry included information on a total of 262 cases. Twenty-three (9%) patients suffered from malignancies. In 78% of these patients, the malignancy itself or the treatment modalities instituted for the carcinoma was the precipitating factor of CAPS. Only 39% of CAPS patients with malignancies recovered in comparison to 58% of patients without malignancies (p = 0.07). Treatment modalities, however, did not differ significantly between these patients. Infections were not evident as precipitating factors for any of the malignancy patients. The mean age of patients with malignancies was 9 years older than the average age of other patients with CAPS and the prevalence of SLE was significantly less common than in patients without malignancy. Malignancy may play a pathogenic role in patients with CAPS, whereas infections are more important as triggering factors in patients without malignancies. CAPS patients with malignancies are generally older than CAPS patients without malignancies; they generally have the worst prognosis of the entire CAPS cohort.
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PMID:The role of malignancies in patients with catastrophic anti-phospholipid (Asherson's) syndrome. 1752 49

Current therapeutic and diagnostic resources have turned systemic lupus erythematosus (SLE) into a chronic disease by reducing mortality rates. The exact contribution of disease activity and disease related damage to mortality is not well studied. The aim of this study was to describe the current causes of death (COD) in a multinational European cohort of patients with SLE in relation to quantified measures of disease activity and damage. Prospective five-year observational study of case fatalities in SLE patients at 12 European centres was performed. Demographics, disease manifestations, interventions and quantified disease activity (by ECLAM and SLEDAI) and damage (by SLICC-DI) at the time of death were related to the various COD. Ninety-one case fatalities (89% females) occurred after median disease duration of 10.2 years (range 0.2-40) corresponding to a annual case fatality of one for each of the participating cohorts. Cumulative mortality correlated linearly with disease duration with nearly 10% of fatalities occurring in the first year and 40% after more than 10 years of disease. Death occurred during SLE remission in one third of cases. In the remaining cases a mixture of disease activity (median ECLAM 5.5, median SLEDAI 15) and accrued damage (median SLICC-DI 5.0) with opposing relationships to disease duration contributed to death. Infections and cardiovascular events were the most frequent COD in both early and late fatalities with no gender differences for type of COD, disease activity, damage or comorbidity. In Europe, case fatalities have become uncommon events in dedicated SLE cohorts. The bimodal mortality curve has flattened out and deaths now occur evenly throughout the disease course with infectious and cardiovascular complications as the main direct COD in both early and late fatalities. Accrued damage supplants disease activity over time as the main SLE specific contributor to death over time.
Lupus 2007
PMID:Current causes of death in systemic lupus erythematosus in Europe, 2000--2004: relation to disease activity and damage accrual. 1757 31

Ocular manifestations of lupus are fairly common, may be the presenting feature of the disease and can be sight-threatening. Almost any part of the eye and visual pathway can be affected by inflammatory or thrombotic processes. Ocular pain and visual impairment require urgent assessment by an ophthalmologist. Infection should be excluded. Optic neuritis and ischaemic optic neuropathy may be difficult to distinguish. Scleritis and severe retinopathy require systemic immunosuppression but episcleritis, anterior uveitis and dry eyes can usually be managed with local eye drops. Vaso-occlusive disease, particularly in the presence of antiphospholipid antibodies, requires treatment with anticoagulation and proliferative retinopathy is treated with laser therapy. Hydroxychloroquine rarely causes ocular toxicity at doses under 6.5 mg/kg/day. When this has occurred, it has been associated with more than 5 years of drug exposure.
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PMID:Ocular manifestations of systemic lupus erythematosus. 1768 81

This study demonstrates demographic, clinical and laboratory characteristics with special reference to infections in Saudi patients with SLE. One-hundred and ninety-nine patients with SLE treated at Riyadh Armed Forces Hospital, Saudi Arabia over a period of 15 years (1990-2005) were retrospectively reviewed. There were 162 females and 37 males (4.4 : 1) with an average age of 35 years at onset of disease. Duration of diseases ranged from one to 23 years with a mean of 7.23 years. Some of the clinical characteristics of SLE patients observed were nephritis (53.7%), fever (53.26%), neuropsychological disorder (36.18%), malar/butterfly rash (27.6%), pulmonary disorder (22.6%), photosensitivity (21.6%), cardiac involvement (21.1%) and oral ulcers (19.09%). Infection was the major complication with 58.79% of SLE patient having suffered from various infections. A total of 22 species of pathogens including gram positive and gram negative bacteria, viruses and fungi were isolated from 117 SLE patients. Single to multiple episode of infection with various pathogens were recorded however, majority of patients harboured one or two species of pathogens. Bacterial infection was predominant (78.6%) followed by viral (28.2%) and fungal (28.2%) infections. Forty-four percent of SLE patients were found to be infected with organisms classified as opportunistic. The high incidence of infections in SLE patients may be attributed to the multiple intrinsic and extrinsic risk factors including deficiency of complement (C3 and C4), disease activity, renal impairment, use of glucocorticoid and cytotoxic drugs. It is concluded that more judicious use of corticosteroids and other immunosuppressive agents will be critical to limit the infections in SLE and a high alert and close monitoring of patients will ensure optimal patient outcome, both in terms of morbidity and mortality.
Lupus 2007
PMID:Systemic lupus erythematosus and infections: a retrospective study in Saudis. 1772 72

Infection, particularly pneumonia, is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). This study was performed to assess the prevalence, causative organisms, and outcomes of community-acquired pneumonia (CAP) in Thai SLE patients, and determine the predicting factors for death. A retrospective chart review of adult SLE patients, age >16 years, seen at the Division of Rheumatology, Chiang Mai University over an 18 year period was carried out. Cases diagnosed with CAP were selected for this study. Of 542 SLE patients, a total of 56 episodes of CAP occurred in 52 patients. Their mean age +/- SD and duration of SLE were 37.98 +/- 11.48 years and 34.99 +/- 54.53 months, respectively. Thirty-three CAP cases (58.9%) occurred within the first year of diagnosis with SLE. The causative organisms identifiable in 40 patients (71.5%) were Mycobacterium tuberculosis in 12, Nocardia spp in 6, Aspergillus spp in 5, Staphylococcus aureus in 3, Pneumocystis carinii, Haemophilus influenzae, Escherichia coli, and Pseudomonas aeruginosa in 2 each, and Acinetobactor baumanii, Burkholderia pseudomallei, and Strongyloides stercoralis in 1 each. The remaining 3 patients had mixed bacterial infection. The overall mortality rate was 26.8%. Use of high dose prednisolone (> or =15 mg/day), and ventilator support were significantly associated with death.
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PMID:Community-acquired pneumonia in Thai patients with systemic lupus erythematosus. 1787 30


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