PURPOSE OF REVIEWThis review examines evidence relating environmental factors to the development of systemic lupus erythematosus (SLE).
RECENT FINDINGSThe strongest epidemiologic evidence exists for ...the associations of silica, cigarette smoking, oral contraceptives, postmenopausal hormone therapy and endometriosis, with SLE incidence. Recent studies have also provided robust evidence of the association between alcohol consumption and decreased SLE risk. There are preliminary, conflicting or unsubstantiated data that other factors, including air pollution, ultraviolet light, infections, vaccinations, solvents, pesticides and heavy metals such as mercury, are related to SLE risk. Biologic mechanisms linking environmental exposures and SLE risk include increased oxidative stress, systemic inflammation and inflammatory cytokine upregulation, and hormonal triggers, as well as epigenetic modifications resulting from exposure that could lead to SLE.
SUMMARYIdentifying the environmental risk factors related to risk of SLE is essential as it will lead to increased understanding of pathogenesis of this complex disease and will also make risk factor modification possible for those at increased risk.
A question most physicians hear almost daily is “Doctor, which vitamins or supplements do you recommend that I take?” This was a question that my colleagues and I set out to answer in the Autoimmune ...Disease Prevention ancillary study in the VITAL trial.1 Now, when my patients, colleagues, or friends ask me, I can point to our research findings, which suggest that for women age 55 years and older, and men 50 years and older, marine omega-3 fatty acids (fish oil) 1000 mg a day, and vitamin D 2000 IU a day—the doses used in VITAL—lead to a 22% reduction in all autoimmune diseases with vitamin D, and a 15% reduction in the same with fish oil supplementation over 5.3 years of randomised follow-up. ...it may be that this supplement at least is more effective among people with an underlying genetic or environmental propensity for autoimmune disease and we hope to investigate this hypothesis. Many autoimmune diseases occur and have similar pathogenesis across the age spectrum, such as psoriasis and rheumatoid arthritis, while others, such as type I diabetes, systemic lupus erythematosus, and multiple sclerosis, have their peak onsets much younger than the VITAL age range, and, lastly, diseases such as polymyalgia rheumatica and giant cell arteritis, and myasthenia gravis are not seen in children and young adults.
When phase 2 trials of treatments for systemic lupus erythematosus (SLE) show positive results, I am delighted but try not to get my hopes up; there have been too many phase 3 trial failures. ...However, the recent Food and Drug Administration approval of voclosporin and belimumab for lupus nephritis and anifrolumab for nonrenal SLE have put wind in the sails of the SLE community. These are the first approvals of new medications for the treatment of SLE since the 2011 approval of belimumab for nonrenal SLE and the 1955 approval of hydroxychloroquine. Lupus is a paradigmatic autoimmune disease, and its . . .
Abstract Objective To perform a systematic review of the literature regarding the epidemiology of the association between systemic lupus erythematosus (SLE) and atherosclerotic cardiovascular disease ...(CVD), including the increased risk for CVD, as well as the risk factors responsible for development of CVD in patients with SLE. Methods We followed the PRISMA guidelines to systematically search the PubMed database from inception to June 2012. Studies were selected using predefined eligibility criteria, and 2 authors independently extracted data. The risk of bias was measured for each study using a domain-based assessment. Results We report on 28 studies that met criteria for inclusion in our analysis. We found strong epidemiologic evidence that SLE patients have an increased relative risk of CVD compared to controls. There is limited information regarding relative CVD mortality risks among SLE patients. Traditional CVD risk factors, including age, male sex, hyperlipidemia, smoking, hypertension, and CRP, are associated with CVD risk among SLE patients. Several SLE-specific factors, including disease activity and duration, and possibly specific manifestations and therapies, further increase risk. Several risk factors, such as disease activity and glucocorticoid use, are closely associated, making it difficult to disentangle their effects. Conclusions CVD risk among SLE patients compared to the general population is at least doubled. While older SLE patients appear to have the highest absolute risks of CVD, young women have alarmingly high relative risks, given the rarity of CVD in the comparison general population. Both traditional and SLE-specific risk factors are important, although there are discrepancies within the literature.
There is growing evidence that preceding the diagnosis or classification of systemic lupus erythematosus (SLE), patients undergo a preclinical phase of disease where markers of inflammation and ...autoimmunity are already present. Not surprisingly then, even though SLE management has improved over the years, many patients will already have irreversible disease-related organ damage by time they have been diagnosed with SLE. By gaining a greater understanding of the pathogenesis of preclinical SLE, we can potentially identify patients earlier in the disease course who are at-risk of transitioning to full-blown SLE and implement preventative strategies. In this review, we discuss the current state of knowledge of SLE preclinical pathogenesis and propose a screening and preventative strategy that involves the use of promising biomarkers of early disease, modification of lifestyle and environmental risk factors, and initiation of preventative therapies, as examined in other autoimmune diseases such as rheumatoid arthritis and type 1 diabetes.
AbstractObjectiveTo investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk.DesignVitamin D and omega 3 trial (VITAL), a nationwide, randomized, ...double blind, placebo controlled trial with a two-by-two factorial design.SettingNationwide in the United States.Participants25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment.InterventionsVitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence.Main outcome measuresThe primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others.Results25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease.ConclusionsVitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo).Study registrationClinicalTrials.gov NCT01351805 and NCT01169259
Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus that disproportionately affects nonwhites and those in lower socioeconomic groups. This review discusses recent ...data on the incidence, prevalence, and outcomes of patients with lupus nephritis with a focus on low-income US Medicaid patients. We also review recent guidelines on diagnosis, treatment, and screening for new onset and relapses of lupus nephritis. Finally, we discuss the management of lupus nephritis from a rheumatologist’s perspective, including vigilance for the common adverse events related to disease and treatment, and we review prevention and new treatment strategies.
Abstract Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between ...genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose–response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.
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