Lupus

Sex and Gender-based Analysis of this topic

Definition
Systemic lupus erythematosus (SLE or lupus) is a chronic and severe autoimmune disorder in which the body produces antibodies that attack healthy tissues leading to inflammation and damage to various body tissues. Lupus can affect the skin, joints, and internal organs including the kidneys. It is estimated that approximately 15,000 (1 in 2,000) Canadians are affected with SLE. [1].
 
The exact causes of lupus are not known, but research points to complex interactions between genetic and environmental factors [2-6]. It is thought that environmental exposures may trigger the onset of lupus in genetically predisposed individuals. Environmental exposures can also aggravate lupus symptoms in individuals with the disorder.   

Laboratory and/ or epidemiological studies have found associations between a range of environmental exposures and lupus. Environmental exposures studied include: mercury [7-9], occupational exposure to silica [10-11], organic solvents (such as trichloroethylene (TCE) [12], air pollution [13], phthalates [14], hair dyes [15], cosmetics [16-18], industrial pollution[19], and hazardous waste sites [20]. Exposure to UV-light, certain infections, smoking, excess stress, and some drugs are additional exogenous factors associated with lupus. The strength of the evidence which suggests links between such exposures and lupus varies across studies and outcomes can be conflicting [21]. In the case of phthalates, it remains unclear whether the link observed between phthalate exposure and the onset of lupus in mice holds true for humans. 
 
 
Sex Issues
Lupus is a condition that overwhelmingly affects women of childbearing age. In Canada, it is estimated that between the ages 15 and 45, eight to 10 times more women than men get lupus.[22-23], while the rates between men and women are similar for  those under 15 and over 45 [24]. The symptoms of the disease are the same in men and women. The reason for the skewed female/ male ratio is unknown, but hormones, especially estrogen in women, are considered to play a potential role [25, 26]. There is mixed evidence on the role of menarche, menopause, and the use of exogenous estrogens and the risk of developing lupus [27, 28]. 

Women and men experience contaminant exposures differently due to physiological, biological, hormonal and social differences [29]. Thus, environmental exposures may trigger different responses in genetically susceptible men and women.
 
 
Gender Issues
Gender can influence why, how, and when individuals experience contaminant exposures [30]. Women are the primary users of cosmetics, including lipsticks and hair dyes, both of which have been associated with lupus in some studies, although data is limited [31-33]. Women’s exposure to phthalates (endocrine disrupting compounds widely found in cosmetics and many other consumer products), for instance, is estimated to be high, especially in the 20-40 age group [34].  

High level occupational exposure to silica is more common in traditionally male dominated occupations such as mining, sandblasting, quarrying and farming. However, even low-level silica exposure, which is present in a wide range of occupations is associated with an increased risk for lupus and could be a significant environmental trigger among some women [35, 36]. In the workplace, women may experience contaminant exposures differently than men, owing to sex and gender differences [37]. Women’s roles as traditional caregivers, often responsible for washing, cleaning and laundering may expose women to contaminants in water and those brought into the home on the clothing and equipment of other family members. 
 
 
Diversity
There is considerable evidence of significant lupus variations among different ethnic groups [38-40]. In Canada and the US, lupus disproportionally affects individuals of African, Hispanic, and Chinese origin. Lupus also disproportionally affects Aboriginal peoples, with one study showing prevalence to be twice as high in North American First Nations compared to non-Natives [41]. In the US, lupus occurrence is three to four times higher among African-American women compared to Caucasian women [42, 43]. This suggests the importance of genetic predisposition to lupus, however, social factors are also critical, such as differences in socio-economic status and access to care and treatment [44]. For instance, lower socio-economic status is positively associated with greater disease activity, poorer physical functioning, and greater depressive symptoms [45]. Residents living near industrial emissions or environmental contamination have shown higher prevalence of lupus [46, 47].
 
 
Critique
Compared to the US, there is limited data on lupus in Canada [48]. Only a handful of Canadian studies are available, one of which demonstrates that current lupus estimates may underestimate lupus prevalence in Canada due to inconsistent data collection techniques used across different studies [49]. 

Given the lack of data, autoimmune diseases such as lupus which overwhelmingly affect women should be included as part of national surveys including the Canada Health Measures Survey and the National Longitudinal Survey of Children and Youth. Further, ongoing biomonitoring studies on exposure to a broad range of contaminants are crucial in regards to lupus. 

Unlike genetic factors, environmental exposures are modifiable and thus, preventable. As such, there is a strong need for additional research to identify and characterize the specific exposures that contribute to the incidence and aggravation of lupus [50].
 
 
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