Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis and chronic polyarthritis as the main clinical manifestation. It occurs in all ethnic groups and has a worldwide average prevalence of 1%. The prevalence of rheumatoid arthritis in most Western countries is 0.5% to 1%. The lowest is in some Asian countries, such as Japan and China. The disease occurs mostly in young adults between the ages of 20 and 50, and there are significant gender differences, with the incidence in women being two to three times that of men, while the incidence in women increases with age, with the peak incidence being before the age of 45.
The etiology of rheumatoid arthritis has not yet been elucidated, and Spector et al. found that the consistent rate of rheumatoid arthritis in identical twins was 20%, which means that nearly 80% of rheumatoid arthritis is caused by environmental or other non-genetic personal factors.
A. Lifestyle habits and environment
1.Smoking and alcohol consumption
Smoking and alcohol consumption is a behavioral risk factor. a population-based case-control study by Voigt et al. found that women who smoked 20 boxes or more per year had an OR of 1.5 (1.0 to 2.0). Few studies have reported on the relationship between alcohol consumption and rheumatoid arthritis.
2. Dietary factors
A population-based case-control study conducted by Shapiro et al. that included 324 new cases and 1,245 controls. found that consumption of grilled or boiled fish was associated with a reduced risk of rheumatoid arthritis, but not with other types of fish. It may be that the abundance of n-3 fatty acids in fish helps prevent the development of rheumatoid arthritis.
3. Environmental climate
Chinese scholars also found that the occurrence of rheumatoid arthritis was associated with dampness and coldness in the living and working environment through case-control studies, with an OR of 3.87 and 28.26, respectively. it is believed that cold and dampness act as a systemic stimulant, acting on the immune system of people with certain genetic characteristics, causing them to change and thus contributing to the development of rheumatoid arthritis. In addition, cold and dampness, as adverse environmental factors, may trigger or exacerbate the action of certain pathogenic factors, thus causing rheumatoid arthritis to occur through autoimmune mechanisms. No such reports have been made abroad. Therefore, the relationship between cold and humidity and rheumatoid arthritis requires further study.
4.Socio-economic status
A prospective study by Bankhead et al. found no tendency for the incidence to increase with decreasing social class. The authors concluded that although some studies have suggested that poor socioeconomic status is associated with poor outcomes in rheumatoid arthritis, this may be related to differences in health behaviors or co-morbidities rather than a direct effect of socioeconomic status on the disease.
II. Infection factors
A study by Darwish et al. found that patients with rheumatoid arthritis had 2.2 times more history of tonsillitis than controls. Some scholars believe that certain childhood infections are associated with rheumatoid arthritis. It has been reported that infectious factors can directly cause rheumatoid arthritis without multiple pathways of autoimmune action, as infectious factors may be the primary determinants and the easiest to correct or clear. However, an epidemiological study conducted by Symmons et al. with a case-control approach found no difference in the history of infection in childhood between cases and controls.
1. Bacteria
Rheumatoid arthritis is associated with Mycobacterium infection, and IgG and IgA antibodies to Mycobacterium were initially found to be present in the sera of patients with rheumatoid arthritis, and the IgG and IgA antibodies against Mycobacterium Hsp60 were significantly higher than in normal subjects. The high expression of Hsp60 was also found in animal experiments.Liu et al. examined the proliferation of primary lymphocytes of four different staphylococcal endotoxins (SEs) in 31 patients with rheumatoid arthritis and found that the proliferative response to the four SEs was lower in patients with rheumatoid arthritis than in normal controls, which was considered to reflect only the general immune regulatory status of patients with rheumatoid arthritis and did not indicate a relationship between SEs and rheumatoid arthritis There is a relationship between the disease course. In certain inbred strains of mice, peptidoglycans with bacterial cell wall fragments, such as those of Streptococcus and other bacteria, induced disease similar to rheumatoid arthritis. This not only supports an important role for bacteria in rheumatoid arthritis, but also suggests that the current concepts of infection and autoimmune disease are broad and overlap with each other.
2. Viruses
Patients with rheumatoid arthritis have higher than normal antibody positivity and titers for anti-EB virus capsid antigen (EBVCA), and certain polysaccharide components of EBVCA share structural similarities with the third polymorphic region of DR4. The antibody titers against EBV nuclear antigen (EBNA), EBVCA, and early antigen (EA) in the sera of patients with rheumatoid arthritis were significantly higher than those of normal subjects, and EBVBamHK240bp DNA fragments were amplified from cells shed from synovial membranes of patients with rheumatoid arthritis. These data support to some extent the evidence of EBV infection. detection by Mousavi et al. found cytomegalovirus (CMV) and EBV DNA measured in the synovium of 6% of patients with rheumatoid arthritis and concluded that these viruses are associated with disease development in a minority of patients with rheumatoid arthritis.
Third, individual factors
1.Obesity
Symmmons et al. found in a population-based case-control study that obesity (BMI ≥ 30) increased the risk of rheumatoid arthritis (OR 3.74, 1.14-12.2), while overweight people (BMI 25-29) did not have an increased risk. It is thought that this may be related to estrogen metabolism in obese individuals. Voigt et al. found a higher risk in those with high BMI than in those with low BMI, suggesting that it may be that endogenous estrogen is increased in obese individuals, especially in postmenopausal women. But other scholars’ cohort study did not find a significant correlation between obesity and rheumatoid arthritis development.
2, psychosocial factors
One study found that more rheumatoid arthritis patients lived in families with high conflict (OR5), low aggregation (OR2) and low expression (OR2.5) compared to controls. However, some scholars did not find that psychosocial factors such as early death of parents and mental burden were related to the development of rheumatoid arthritis, and concluded that the pain and movement disorders caused by rheumatoid arthritis caused patients to change their original personality traits, i.e., psychosocial factors were the result rather than the cause of rheumatoid arthritis. Conway et al. also did not find that patients with rheumatoid arthritis had excessive life events in the year before the onset of the disease.
3. History of trauma, surgery and blood transfusion
Arwish et al. found that a history of trauma was also a strong risk factor (OR4), and Chinese scholars have made similar findings, suggesting that trauma causes changes in the body’s immune function, resulting in increased susceptibility to certain pathogenic factors or exacerbating pre-existing immune dysfunction. Trauma may also have a direct pathogenic effect by producing degenerative antigens through joint damage, thereby promoting autoimmune reactions, or by introducing harmful factors directly into the joints through trauma and causing disease.
Fourth, female related factors
1, menarche, pregnancy, childbirth and lactation
The earlier the first pregnancy, the lower the risk of rheumatoid arthritis, and a bad pregnancy (i.e., less than 25 weeks of gestation) does not change the risk of rheumatoid arthritis. The protective effect of pregnancy was not associated with the use of oral contraceptives, HLA-DR4 positivity, or family history of rheumatoid arthritis. a population-based study by Spector et al. found a protective effect of pregnancy, oral contraceptives on rheumatoid arthritis. daSilva et al. suggested that pregnancy alleviates the course of rheumatoid arthritis and may be a predisposing factor to alter the development of rheumatoid arthritis later in life. These factors include increased estrogen, increased pregnancy-associated glycoproteins, decreased galactose-free IgG and stimulation of the immune system by paternal HLA antigens.
2. Oral contraceptives
There have been numerous studies of the relationship between oral contraceptive pills (OCP) and rheumatoid arthritis, but the results vary widely. Most case-control studies have shown a protective effect of OCP, and fewer cohort studies have shown results that support this conclusion. Hospital-based studies have shown a protective effect in former and current users compared to never users of OCP, and a protective effect in long-term users. However, population-based studies did not support this conclusion, so the authors concluded that there is no conclusive evidence for a protective effect of OCP in rheumatoid arthritis.