Rheumatoid arthritis who is at risk

What triggers an arthritis flare? Rheumatoid arthritis. Autoimmunity: From bench to bedside [Internet]. Arthritis-Related statistics. Updated July 18, Holoshitz, J. Curr Opin Rheumatol. Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study. Annal Rheumatic Dis. Overweight and obesity reduce the likelihood of achieving sustained remission in early rheumatoid arthritis: Results from the Canadian early arthritis cohort study.

Arthritis Care Res. Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies. Annals Rheum Dis. Your Privacy Rights. To change or withdraw your consent choices for VerywellHealth. At any time, you can update your settings through the "EU Privacy" link at the bottom of any page.

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Genes That May Play a Role Certain variants in other genes may also contribute, including: STAT4, a gene that plays an important role in the regulation and activation of the immune response TRAF1 and C5, two genes associated with chronic inflammation PTPN22, a gene associated with both the development and progression of rheumatoid arthritis. What is the difference between rheumatoid arthritis and osteoarthritis? How Rheumatoid Arthritis Is Diagnosed. Was this page helpful?

Thanks for your feedback! Sign Up. What are your concerns? Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. However, it's not yet known what triggers this. Your immune system normally makes antibodies that attack bacteria and viruses, helping to fight infection. If you have rheumatoid arthritis, your immune system mistakenly sends antibodies to the lining of your joints, where they attack the tissue surrounding the joint.

Those with RA were more likely to have testosterone levels outside the normal range. Some participants with RA then received serum testosterone therapy, and the activity of their RA reduced. During and after menopause, some females with RA experience a decline in physical ability, according to results of a different study.

This finding also suggests that hormones play a role in the progression of RA. Meanwhile, research in animals and humans suggests that receiving estrogen replacement therapy after menopause may increase the risk of developing RA. RA can develop at any age, but the risk increases as people get older. It is most likely to arise when a person is in their 60s , according to the CDC.

Scientists have found links between smoking and an increased risk of developing RA, even among people with low-level, lifelong exposure to smoke. Also, heavy smokers may have more severe RA symptoms, the research suggests.

It can also make some prescription RA medications less effective. Some researchers believe that stress may play a role in RA. For example, the way the body reacts to stress may worsen symptoms. People with rheumatic conditions often report that their symptoms first appeared shortly after traumatic or stressful experiences, and many people find that stress causes RA symptoms to flare up.

Here, find some tips on managing stress. Also, researchers associate obesity with several health issues, such as metabolic syndrome, that can exacerbate RA symptoms. For example, inflammation is a common feature of both obesity and metabolic syndrome. Here, learn about 10 effective weight loss strategies. Results of a study from Taiwan suggest that socioeconomic status may affect the risk of developing RA.

The authors found that people had a higher chance of developing it if they lived in an area where a low monthly income was common. This could be due to factors such as occupation, housing conditions, stress, and diet, but access to healthcare may also play a role, as the researchers note. In recent years, knowledge of the inflammatory mechanisms at work in obesity has steadily increased. White adipose tissue WAT is now postulated to act as an endocrine organ capable of releasing cytokines such as C-reactive protein, leptin, tumor necrosis factor, and interleukin 6 , which may predispose individuals to autoimmune inflammatory diseases by exacerbating inflammation Thus, many studies have focused on assessing the association between obesity and the risk of developing inflammatory diseases such as RA.

Although data on the relationship between obesity and the risk of is conflicting, obesity is an important and increasingly common comorbidity, even on first presentation of RA Increasing evidence that the period of pre-clinical inflammation and autoimmunity can be prolonged suggests that it is of pressing interest to more fully take into account obesity and other environmental risk factors that are potentially modifiable and which may therefore help lower the risk of developing RA in susceptible patients.

The results of several meta-analyses, mostly consisting of retrospective studies, support the contention that BMI is directly related to the risk of developing not only RA, especially in female populations, but also of seronegative RA in particular — However, by focusing on studies conducted when patients are in a pre-clinical period or on those with UA, the influence of obesity in the onset of RA remains controversial and only partially understood.

Rakihe et al. However, in another case-control study, that also evaluated the influence of obesity in patients with pre-arthritis vs. These results suggest that ACPA and obesity can act synergistically, constituting a risk factor for the development of RA, as well as Chaparro-Sanabria et al.

These results also suggest that women with both risk factors are likely to progress to clinical development of RA most rapidly of any population Thus, excess adipose tissue does not seem to promote the development of ACPA, although being overweight and obesity can foster systemic inflammation, which hastens the pathogenesis of RA.

Thus, Moreno-Fresneda et al. In conclusion, obesity is a potentially modifiable risk factor that may contribute to the onset of clinical arthritis due to exacerbation of the pro-inflammatory status in these patients , The lung parenchyma has been described as a possible site of onset of autoimmunity in RA, although the role of the pulmonary microbiome as a mediator of inflammation has only recently emerged , Of the different mucosal sites where RA could be initiated, the lung has been the most studied to date in RA.

Lung disease, both airway and parenchymal, and lung-generated autoimmunity, can be present before the initiation of joint symptoms, suggesting that immune reactions in the lung may be involved in the onset of RA-related autoimmunity , — Airborne pollutants such as textile dust, silica and cigarette smoke increase epithelial permeability with the accumulation of inflammatory mediators , While the particular immunologic pathways occurring in the lung prior to the onset of RA have yet to be entirely elucidated, data support the hypothesis that autoantibody development is initiated in the lung.

Willis et al. These findings suggest that the lungs not only participate in the citrullination of proteins, but also that they are either an early target for injury secondary to autoimmunity or that they play a role in its development Demoruelle et al.

Signs of inflammation, such as bronchiectasis, bronchial wall thickening and centrilobular opacities, were common in at-risk individuals and were similar to the airway abnormalities seen in patients with early RA.

Similarly, Joshua et al. These findings support an important pathogenic link between systemic autoimmunity and the lung, contributing to RA development. Scher et al. Additional data also suggest that mucosal lung mucosa included processes play a role in the transition from pre-RA to classified RA.

In a cohort of subjects with serum samples obtained pre- and post-RA diagnosis, Kelmenson et al. Although this finding does not directly involve the lung, it suggests that IgA-dominant mucosal processes likely help the transition to clinically apparent inflammatory arthritis. Furthermore, there is evidence suggesting that smoking may be related to the translocation of supraglottic bacterial species, such as Porphyromonas and Prevotella, to the lungs, thereby leading to increased peptidylarginine-deiminase PAD activity and airway inflammation This is in line with previous studies involving early RA subjects that reported dysbiotic states at other mucosal sites, such as the gut and gingiva, with decreased taxa diversity If autoimmunity in RA originates in the lung, additional pathways must be involved in the transition from mucosal inflammation to the ultimate joint inflammation.

Mechanisms that have been proposed include a epitope spreading to a joint specific antigen, shared antigenic target between the lungs and joints and immune complex deposition in the joints that drives finally to RA development More studies are needed to entirely understand the relationship between mucosal processes, as well as joint disease in RA, from the early triggering and dissemination of autoimmunity to the ultimate development of joint disease.

It is worth noting the great interest in recent years surrounding Porphyromonas gingivalis as a possible stimulus for the development of RA. This is because periodontitis PD , is a disease that is more frequent in subjects with RA than in healthy populations , and P.

It is the only bacterium known to express the PAD enzyme, which is responsible for the process of protein citrullination This can lead to the generation of self-antigens, thereby producing chronic inflammation, characterized by the presence of pro-inflammatory cytokines and TNF Indeed, Cheng et al.

Mikuls et al. Together, these findings suggest that infection with P. Smoking is the most important environmental risk factor for RA development. Several theories have been put forward as to how smoking might predispose individuals to RA. Smoking leads to higher expression of the PAD2 enzyme, that increase the mechanisms of citrullination in the lung However, it remains unclear how tolerance against citrullinated proteins is broken and ACPAs are produced, since citrullination also occurs under physiological conditions.

The relationship between smoking and RA present several aspects that contribute to an increased risk of developing RA. Smoking has also been associated with the presence of RF even in the absence of RA This suggests that there may be biological interactions between RA-related autoimmunity and the development of RA. Second, because smoking is associated with increased PD and lung, this risk factor may drive inflammation and alterations in local immunity.

On the other hand in an FDR study of RA patients, joint inflammation, and tenderness was associated with smoking even in the absence of RA-related autoantibodies. This raises the possibility that smoking, in addition to its systemic effects, may also have direct joint effects that may be related to the future onset of IA Furthermore, several epidemiological studies have shown that smoking appears to be a greater risk factor for RA in men than in women , This observation could indicate that there are sex-related differences in the effects of smoking, or that women have other stronger risk factors for developing RA.

However, the question is where to place smoking in the context of RA onset. Really, it is unclear whether exposure to smoking triggers the initial autoimmunity or if it drives the propagation of autoimmunity.

Other studies, however, suggest that it is the duration of smoking, more than the intensity of it, that amplifies risk of RA 51 , , Furthermore, tobacco can interact with other risk factors. A prospective study involving 55 ACPA-positive individuals at risk for developing RA showed that smoking and being overweight increased the risk of development of arthritis after 13 months of follow-up.

So, these results show the importance of lifestyle factors in the development of RA. To conclude, smoking is an important risk factor associated with the onset of RA, mainly in ACPA-positive individuals. However, this topic needs to be considered in future clinical research aimed at disease prevention as a modifiable risk factor.

The dust contained silica, pulverized cement, glass fibers, asbestos, and other materials. In other cohort of Malaysian women, occupational exposure to textile dust was also found to be significantly associated with an increased risk of developing RA In addition, the exposure to inhaled particles from air pollution, have also been linked to an increased risk for RA.

However, it is difficult to assess the true exposure to air pollution and accounting for other factors such as specific components of pollution that may vary by locality , Several infectious agents have been implicated in the development of RA based on a higher frequency of positive viral serologies or their presence in the fluid synovium of RA patients.

In addition, previous studies show that RA exhibits seasonal tendencies, suggesting the influence of viral infections on the onset of RA. However, their role as an agent for disease remains controversial Pathogen-based infections such as the Epstein-Barr Virus EBV , Proteus, Mycoplasma, coronavirus, ambient parainfluenza, and metapneumovirus have been associated with an increased incidence of RA Few studies have investigated the potential link between respiratory viral infections and the development of RA , In a population-based case-control study, previous respiratory tract infections treated with antibiotics sinusitis, tonsillitis and pneumonia , showed no association with an increased risk of RA Another study, showed that viral infection symptoms confirmed by questionnaire were more frequent in patients who had experienced a new-onset RA during the previous year compared to healthy controls, although this was a small-sized study involving 59 RA patients and 69 controls In a national cohort study, it was observed that individuals hospitalized for a serious infection were at increased risk for a subsequent diagnosis of autoimmune diseases, including rheumatoid arthritis Individuals with multiple hospitalizations for infections and persons hospitalized for a serious infection shortly before an autoimmune diagnosis were at greatest risk, and no differences were found between being hospitalized for a viral infection and other types of infection.

This study suggests that all infections requiring hospitalization increase the risk of developing an autoimmune disease regardless of the type of infection, albeit in a time-dependent manner. However, rather than directly initiating autoimmunity, serious infections might accelerate a pre-existing autoimmune condition to progress to clinical disease.

Viral arthritis is distinct from autoimmune disease-associated polyarthritis, and a differential diagnosis should be performed. Viral arthritis are usually self-limiting, and treatment with immunosuppressants is not required in most cases.

In summary, infectious agents may play some role in the development of the disease in the context of genetic predisposition and not in isolation, but rather by interacting with other risk factors.

The presence of different auto-Abs in serum can be detected years before RA disease onset 3 , , Several longitudinal studies have linked the presence of ACPA to the onset of clinical arthritis 8 , — In fact, the value of ACPA levels in predicting arthritis development is unclear.

Two studies supported an association between ACPA levels and arthritis development 21 , while two others did not 93 , In addition, the number of epitopes recognized by ACPA was associated with the onset of arthritis in several studies involving ACPA-positive patients with arthralgia — Furthermore, a decrease in galactosylation and an increase in the core fucosylation of serum ACPA IgG1 prior to the RA onset has been reported, indicating that these autoantibodies adopted a more inflammatory phenotype On the other hand, it is worth noting that the effect of ACPA on the risk of developing RA can be potentiated by its association with other risk factors such as obesity The value of RF in the preclinical phase of RA has also been studied 8 , 21 , — Two studies, using the same cohort, demonstrated the additive presence of RF in association with arthritis development in ACPA-positive patients 13 , No ACPA-negative patients were included in the previously mentioned studies.

Other studies lost the single value of the RF-positive results after adjusting for the concomitant presence of ACPA 8 , , However, the results from one study suggested that high vs.

Anti-carbamylated protein anti-CarP antibodies also belong to the group of anti-post-translationally modified protein antibodies AMPA that have been described in RA. The relationship between the presence anti-CarP antibodies and the risk for RA development during the preclinical phase of RA remains controversial. In addition, the presence of these antibodies were associated with other non-SE alleles suggesting that additional mechanisms may be influencing the risk of developing RA Nonetheless, it is important to highlight the fact that the available evidence on this issue poses some limitations: the absence of an auto-Ab negative reference group, the lack of a standard definition of arthralgia in the inclusion criteria, and some studies involved the same cohort.

Several acute phase reactants, chemokines, cytokines, and other systemic markers have been studied in the preclinical stages of RA Some studies identified an association between CRP or ESR and arthritis development , , while others did not 19 , , , — The only study that showed an association between serum CRP at study entry and development of arthritis included patients with CSA and did not select on the presence of autoantibodies 21 , Studies showing no predictive value for CRP levels were mostly conducted in patients with autoantibody-positive arthralgia 19 , , , — This implies that CRP has a predictive value, particularly, in autoantibody-negative patients.

In conclusion, most results on serological markers of inflammation have not been validated in independent studies. Only CRP has been evaluated in different patient cohorts presenting seropositive arthralgia, although it was shown to be of limited value. There are many clinical, analytical, sociodemographic and environmental risk factors that have been associated with the risk of developing RA. The early identification and prevention of chronic diseases such as RA has aroused great interest in the scientific community due to their far-reaching implications.

In this review, it is observed that the risk factors associated with the onset of RA are very heterogeneous, some of them are modifiable. This highlights the importance of educating citizens about the importance of healthy lifestyle habits in order to prevent chronic diseases. One of the main hurdles is that the risk factors associated with RA are exacerbated by the interaction between them, which makes it quite difficult to determine the individual risk levels of each individual within a given period of time.

To this end, they may allow us to formulate more accurate predictive models than those described thus far. Understanding these mechanisms in depth will help us to improve our knowledge about the development of the disease and to define additional risk factors that could be included in predictive models.

Several studies have attempted to identify risk factors in patients presenting early UA and CSA, with a particular focus on clinical and serological criteria inherent to the individual. However, there are many potentially modifiable factors that can be taken into account during this early stage of the disease, not only in terms of identifying patients at an increased risk of developing RA, but also as to whether patient care should be initiated in order to prevent disease progression.

It should be kept in mind that these factors do not act alone, and that the combination of several factors results in a heightened risk of RA. Thus, it would be very useful to implement the knowledge gained about these factors into a more comprehensive management plan for the care of such patients.