**2. Systemic lupus erythematosus (SLE)**

SLE is a multisystemic and complex autoimmune disease/condition characterized by loss of tolerance to self-antigens and production of high-titers serum autoantibodies with multifactorial etiology, which mainly affect women. The exact etiology of SLE is still unknown but there are various factors that might contribute to the onset of the disease and disease flare [8]. These include a number of environmental factors such as cigarette smoking, alcohol, chemicals and biochemicals, UV light, hormones, and infections caused by viruses, bacteria, and vaccine; all these contribute to induced lupus and disease flares [9]. These environmental factors trigger SLE by altering the epigenetic mechanism [10]. Epigenetic mechanisms which might trigger SLE include histone modification and DNA methylation, in which the cytosine base of DNA undergoes methylation and modification of histone tails including deacetylation, ubiquination, and tri-methylation [11]. In SLE, hypomethylation of DNA from CD4 + T cells takes place and as a result, T cells can function as autoreactive in response to self-class MHC II molecules [12].

UV light causes the main symptoms of SLE and triggers its onset [13]. This ability to induce this disease is dose related, meaning that more radiation causes greater severity in the disease [14]. If UV dose is low, normal apoptosis takes place in keratinocytes, while in high or moderate concentration, fragmentation of DNA, elevation in the expression of IL-1α, and necrosis of keratinocytes take place [14]. In conclusion, intermediate and high dose of UV light causes pro-inflammatory apoptosis and necrosis followed by the discharge of autoantigen and pro-inflammatory cytokines, which might trigger various inflammatory responses [14]. Smoking is also linked with increased risk of SLE and discoid lupus [15]. In addition to the relation between the risk of development of SLE and smoking, smoking is also associated with skin flares in patients with SLE [15]. Smoking also decreases the efficacy of antimalarials, but induces cutaneous lupus erythematosus [16]. No clear link has yet been established between the potential risk of SLE and alcohol consumption because the habit of smoking and alcohol often coexist, which interferes with the exact interpretation of the coexisting risk of development of SLE and alcohol habit [17]. One of the earlier studies has shown that neither past nor current alcohol consumption was associated with the development of SLE [18]. In an Internet-based study, it was found that current drinking habits are inversely associated with the development of SLE [19]. Certain medications are also known to induce lupus-like symptoms. Drug such as procainamide, which is an anti-arrhythmic drug, might induce lupus-like syndrome by acting as an inhibitor for DNA methyltransferase in human T cell lines [20]. Anti-TNF has been used in the treatment of inflammatory arthritis and is known to cause anti-TNF-induced lupus [21]. In addition, recent data suggest the role of estrogen and their metabolites in the pathogenesis of lupus [22–26].
