Progress in epidemiology of rheumatoid arthritis

Progress in epidemiology of rheumatoid arthritis

Rheumatoid arthritis (RA) is a multi-joint chronic inflammatory disease of unknown cause. The American College of Rheumatology (ACR) issued a new set of diagnostic criteria for RA in 1987. The new version has increased diagnostic sensitivity but similar approximation. A review of the prevalence, morbidity and risk factors of RA in epidemiology is presented.

prognosis of rheumatoid arthritis


The prevalence of RA increases with age, and most population studies show that the elderly (65 years or older or over 70 years old) The highest prevalence rate. Among the elderly population, RA with the lower education level had the highest prevalence, and women were slightly higher than men. The large population census in Europe over the past 20 years shows that the prevalence of adult RA is 0.2% (Belgrade) ~ 0.8% (Finland), and the prevalence reported in southern Europe (Italy, Greece, Yugoslavia) is generally low (0.2%). ~0.4%). Compared with the recent prevalence rate, the prevalence of RA in Rochester, Minnesota (1985) was relatively high, and 1.07% in adults. The prevalence of RA varies from place to place around the world. The prevalence of African blacks in urban areas is relatively high. However, the prevalence of RA is generally low in Aboriginal and some rural African blacks. In China and Indonesia, the prevalence of RA in both urban and rural populations is low. Conversely, RA is very common in some well-educated natives in the United States, such as the Qipei in Minnesota, the Pima in Arizona, and the Inupiat in Alaska, while the prevalence of RA is relatively low in other native populations. . The low prevalence among African blacks may be related to poor expression and low survival rates of patients, small sample sizes in the study, inaccurate estimates of prevalence, and large confidence intervals.

Occurrence rate

The incidence of RA is determined by longitudinal investigation, so the incidence of morbidity is usually less than the prevalence study. In addition, even in a large population, the number of new cases is relatively small, so the estimation of the incidence rate is often inaccurate. Studies in Sadebury, Massachusetts, Norwich, Finland, and Finland have shown that the annual incidence of RA among women is higher than that of men, usually 0.2‰ to 0.4‰. The incidence rate is higher in Rochester, Minnesota, USA, and is about 0.75 in adults.

Most studies have reported a decreasing incidence of RA. Regular surveys from the Mayo Clinic, the British General Practitioners, ongoing community surveys in Japan, and long-term surveys of Pima Indians dating back to the past 25 years have shown that the incidence of RA has dropped by 20% to 50%. The proportion of patients with severe disability has also declined, and the age of onset has increased. There are several reasons for this change in the pathogenesis of RA: 1 long-term changes in the potential infectious virulence factors; 2 the use of oral contraceptives and other drugs can protect the population from disease; 3 living standards and health environment The improvement can also affect the occurrence and severity of RA to some extent; 4 genetic drift can increase the expression of protective genes of certain RA; 5 exposure to RA virulence factors with higher incidence The birth of the same generation is gradually disappearing.

Risk factors

★Genetic factors

Family studies of RA patients show that first-degree relatives are at greater risk than illness Relatives are 2 to 4 times higher. Studies on twins have shown that when one of the twins has RA, the other side of the twins has 12% to 15% of the likelihood of RA, while the other of the fraternal twins has only 3% to 4%. The possibility. Its heritability is 60% (hereditary means the proportion of genetic factors in the total incidence of disease).

In the American white, diseased black Africans and the high prevalence of the Chippewa Indians, the haplotype HLA of the major histocompatibility complex (MHC) of RA and II DR4 related. Although DR4 is considered to be the most closely related phenotype of RA, only about 2/3 of patients are DR4 positive, while the DR4 positive rate in the unaffected control group is about 30%. In RA patients who are negative for the DR4 molecule and express the DR1 haplotype, it appears to also have the DR-β allele, which also contains this important nucleotide sequence.

Of the 41 seropositive RA patients, 35 (85%) carried one or more DR-β genes (DR4 positive or DR1 positive, respectively). This common epitope explains most, but not all, of the genetic basis of HLA as a susceptibility to RA. The common epitope is similar to the role of codominant genes, so double genes can further enhance the risk of RA. Carrying two different alleles, including a common epitope, is likely to be more dangerous than carrying two identical alleles, or it is possible that one of these DR-β alleles is experiencing susceptibility . Twins with a common epitope are homozygous and have a higher consistency in RA. The DR4 subtype is not only the basis for RA susceptibility, but also greatly increases the risk of severe RA. Among patients with RA, those with the DR4 subtype were more likely to have X-ray erosion, rheumatoid factor-positive, and rheumatoid nodules than those without.

Although the common epitope is closely related to RA, many people in the population carrying the gene are not ill, indicating that there are other susceptibility genes, one of which is likely Located in the HLA gene region. A genome scan of a large number of RA high-incidence families revealed that there is a constant chain-susceptibility gene on the short arm of chromosome 6, even after removal of the DR-β chain gene, so it is speculated that the site of this linkage gene is very May be in the HLA-III gene region. There is recent evidence that the site of the susceptibility gene is outside the HLA gene region. In the linkage and correlation studies, the latter detected candidate gene sequences. Among the confirmed candidate genes, the gene encoded by tumor necrosis factor (TNF) receptor II has a polymorphism. It is likely that other genes also determine the clinical manifestations of RA, such as Felty syndrome (RA with splenomegaly, leukopenia).

★ Hormone and Fertility Factors

Many circumstantial evidence suggests that hormones can also affect the development and severity of RA: 1 RA is more common than men In women; 2 RA during pregnancy can often be spontaneously relieved, which is related to changes in hormone levels during this period; 3 male RA patients have lower levels of ketone in the blood. The relationship between hormone levels and RA has become a hot topic in research. According to the meta-analysis, clinic- and hospital-based case studies almost unanimously believe that oral contraceptives have a protective effect on RA, whereas population-based case studies have not found such effects. Oral contraceptives can also prevent further exacerbations of RA. Similar to the oral contraceptive study, and the study on the risk of RA after postmenopausal estrogen replacement therapy, but did not reach a consensus, and the endogenous estrogen levels in postmenopausal women with RA were compared with the control group. There is no continuous difference. Studies suggest that fertility is generally low in women with RA, but these findings can make women feel fearful of infertility that may be caused by early onset.

How does fertility produce RA risk? As mentioned earlier, RA often relieves during pregnancy, but after birth, especially in the first 3 months, the original RA may be aggravated again, and The risk of morbidity after delivery in women without previous RA is also greatly increased. Breastfeeding, especially after the first pregnancy, further increases this risk. So how do you explain these findings? The levels of cortisone and estrogen in the body and their anti-inflammatory effects will increase during pregnancy and decrease after delivery, which inevitably leads to the production of pro-inflammatory cytokines (such as TNF-α) in pregnancy. The period declines and declines after childbirth. Increased prolactin levels during breastfeeding have an inflammatory response effect, and unlike pregnancy, this effect is not controlled by increased levels of other hormones in the body, so prolactin also increases the risk of RA.

★Nutrition Factors

More and more studies have shown that nutritional factors can affect the incidence of RA. A large number of baked or grilled fish, especially oil-rich fish such as salmon and trout, can slow the progression of RA because it is rich in fatty acids δ3. Evidence for the role of antioxidant vitamins and trace element complexes, large cohort studies have shown that higher levels of selenium in serum can prevent RA progression, and there are hypotheses that increased selenium levels in serum can temporarily reduce RA incidence. .

Although tea contains several antioxidants, there is no conclusive evidence that coffee and tea consumption is associated with RA. A study showed that tea drinkers had a lower risk of RA than those who did not. The relationship between coffee and RA is more complicated, and the views in the study are inconsistent. One study showed that ingesting coffee increased the risk of RA, but in another study it was found that coffee containing caffeine was not associated with the risk of RA, but decaffeinated coffee (also in caffeine extraction) The trace process of the dissolution process) increases the risk of RA. Further comprehensive assessment of these nutrients is necessary.

★Other factors

Individuals with positive rheumatoid factor testing are at high risk for RA, and the risk is related to the titer of rheumatoid factor. There is ample evidence that smoking (especially large amounts of smoking) increases the risk of developing RA and increases the risk of RA progression. Smokers are more severe than non-smokers, and there is a gene that encodes an enzyme that detoxifies multiple chemicals. People who lack this gene in smokers are more likely to develop severe RA. Smoking also has a certain effect of inhibiting estrogen and reducing immunity, which will affect the occurrence of RA.

Although no infectious agents have been found to be associated with RA, environmental triggering is highly likely, and reports of post-infection arthritis similar to mild RA make infection a possible etiology. If it is caused by infection or environmental toxins, RA should have a certain degree of aggregation in time or space. A prospective RA incidence study in most parts of the UK showed no time-gathering, only a certain degree of spatial aggregation and time-independent, indicating that RA does not have a risk of suggesting infection or environmental toxin risk factors. Sex.


The prognosis for patients with RA is different. Patients obtained in population-based studies often have only mild RA and often relieve symptoms. Most of the subjects detected from the population screening study did not have RA approved by the clinician. In contrast, clinically based research often focuses on patients suffering from pain (biased samples). Most studies on the long-term prognosis of RA are clinically based.

RA patients had a higher mortality rate than patients of the same age or same sex control group. The survival period is generally shortened by 3 to 18 years, and the overall risk of mortality increases by 1.3 to 2 times after a 10-year span. For patients with early loss of function, severe RA, and concurrent comorbidities such as cardiovascular disease, mortality is significantly increased.

RA patients are more likely to die from infection and cardiovascular disease than the general population. Other common causes of death include kidney disease (especially in European patients with a higher proportion of secondary amyloidosis) and iatrogenic gastrointestinal complications. Overall, the risk of malignancy in RA patients does not appear to increase, although the incidence of leukocytosis and lymphoma is higher than expected, in part due to alkylating agent treatment. The incidence of colon cancer is reduced in patients with RA, which is due to the long-term use of non-steroidal drugs, which can prevent colon cancer. Many long-term RA patients have concurrent Sjogren’s syndrome, which increases the risk of lymphoma.

prognosis of rheumatoid arthritis

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