Let's Talk About Rheumatoid Arthritis Causes
From genes to gender, a multitude of factors come together to increase your odds of getting this disease. Knowing which ones you can control will help you stay one step ahead of it.
Among the many frustrating things about rheumatoid arthritis is the fact that who gets it, and why, is still a big unknown. Sure, scientists can point to certain risk factors, but they’ve yet to ID a single cause, quite likely because there isn’t one. Instead, a combination of things—including genetic predisposition, environmental elements, and behavioral factors—come together to create a perfect storm that leads to a cascade of immune reactions impacting the joints. Environmental factors also influence the severity of the disease and intensity of flares. Understanding the variables that influence RA can help you find ways to better control it.
Our Pro Panel
We went to some of the nation’s top RA experts to bring you the most scientific and up-to-date information possible.
Nilanjana Bose, M.D.
Rheumatology Center of Houston
Elizabeth Schulman, M.D.
Rheumatologist and Assistant Professor of Medicine
Weill Cornell Medical College
New York, NY
Dee Dee Wu, M.D.
Rheumatologist and Assistant Attending Physician
Hospital for Special Surgery
New York, NY
Who gets it, and why, is still a bit of a question mark. It's a mistake to think of RA only as an older person's disease. While RA affects about 1% of the population, and while it's mostly women between the ages of 40 and 60, it can strike anyone at any age.
Likely caused by a combination of genetic and environmental factors, juvenile rheumatoid arthritis (now more commonly called juvenile idiopathic arthritis) is an autoimmune disease in which the body’s immune system attacks its own healthy cells. It differs from adult RA in that children often outgrow the disease.
There is no sure way to prevent rheumatoid arthritis. But you can reduce your risk by giving up cigarettes (or better yet, not smoking them in the first place), maintaining a healthy weight, and promoting general wellness through diet, exercise, and stress management.
The source of RA flares, episodes of increased disease activity, isn’t always evident. If you’re having a flare, take a look at what else is going on your life: Overexertion, poor sleep, stress, or an infection are all possible triggers.
What Is Rheumatoid Arthritis Again?
Rheumatoid arthritis (RA) is the second most-common type of arthritis. It affects about 1.3 million people in the United States, 70% of whom are women, according to the Arthritis Foundation. RA primarily attacks your joints but it can also affect other areas of your body. The disease typically develops between ages 40 and 60, although it may also occur in children via a condition called juvenile idiopathic arthritis.
So What Exactly Causes RA, Then?
In RA, your immune system mistakenly attacks your body’s own healthy cells from the inside out, inflaming the lining of the membranes that surround your joints (the synovium). While the synovium of healthy joints is thin and delicate, in joints with RA, the synovium becomes swollen and the synovial cavity, or space between your joints, fills with inflammatory fluid. The result: Pain, swelling, and joint stiffness. In severe cases, RA can even compromise the joint cartilage, leading to the degradation and destruction of cartilage and bone over time.
It’s still a mystery why the immune system turns on the body’s own cells, but researchers have a few ideas. Let’s take a closer look at things that contribute to the development of RA.
Is Rheumatoid Arthritis Genetic?
As if you needed another reason to begrudge the fam: Studies confirm that genetics increase your risk of developing the disease. The inheritance pattern is not totally clear but having a close relative with RA ups your odds of getting it, too. One study found that if your parent, sibling, or child has RA, your likelihood of the disease increases threefold.
Studies of twins offer further evidence. If one identical twin has RA, the other has a 15% chance of developing it as well. For nonidentical twins, the chance is 4%. Given less than 1% of the overall population has RA, the genetic connection is pretty clear.
Which genes, though, is less obvious. Human leukocyte antigen (HLA) genes are believed to play a role, especially HLA-DRB1. These genes help the immune system tell the difference between the body’s own proteins and those from foreign invaders like viruses and bacteria. Research suggests several versions of the HLA-DRB1 gene are associated with RA risk, and more than 80% of RA patients have at least one of them. Other genes linked to RA include PTPN22, STAT4, CTLA4, TRAF1, and C5.
Scientists guesstimate that heritability accounts for about 20 to 50% of your odds of getting RA. (Then again, even if you have no family history of the disease, that doesn’t mean you’re in the clear, either.) As for the other 50 to 80%, researchers have turned their attention to environmental and behavioral factors.
Does Smoking Cause RA?
One thing scientists are pretty sure of: Tobacco smoking is linked with RA. A large study in Arthritis Care & Research shows that women who smoke are 47% more likely than nonsmokers to develop RA. The exact cause and effect is not well understood, but it’s possible that toxic chemicals in the smoke (like nicotine and carbon monoxide) may promote the development of harmful antibodies.
The risk for RA increases in people who have smoked 20 years or longer and have a genetic predisposition to the disease, and smokers are more likely to have severe symptoms and greater joint damage. They may also be less likely to experience remission.
The good news? Quitting can help lower your risk—and the sooner the better. One study found that people who kicked the habit 30 years ago were 37% less likely to develop RA compared with those who quit in the last five years.
Being Overweight Is a Risk Factor
More and more research suggests that carrying too many pounds (a BMI of 25 or more) may increase the risk of RA in those who are genetically susceptible, particularly women. One large comparative study found that obesity accounted for 52% of the reported increase in RA in women from 1985 to 2007. In another study, women who’d been obese for 10 years or longer had a 37% increased risk for RA.
Being obese may also lower your chance of achieving sustained remission by 47%, according to research (and by 25% in people who are overweight). The reason? Fat cells constantly release proteins called cytokines that cause inflammation, which may aggravate your swollen joints. Plus, these inflammatory cytokines are often already circulating in your body if you have RA; adding more to the mix only makes matters more painful.
Your Gender Makes a Difference
Bad news if you’re female: Women are three times more likely than men to develop RA, although that number drops to twice as likely if they are diagnosed after age 50. Curiously, after age 75, RA actually becomes more common in men. The reason could be hormonal: Studies have linked low testosterone levels in men with an increased risk of RA, supporting the theory that testosterone may have a protective effect.
In general, all hormones seem to have a protective effect against RA. During pregnancy, when estrogen increases, women with RA may see a reduction or complete remission of RA symptoms. But when hormone levels decrease after giving birth, symptoms typically return. And women who go through early menopause (when estrogen plummets) are more likely to develop RA than those who experience normal to late menopause.
Is Age a Rheumatoid Arthritis Risk Factor?
Despite what you probably picture with arthritis, RA can occur at any age. Children as young as two can develop juvenile idiopathic arthritis (also called juvenile rheumatoid arthritis). But statistically speaking, most people are first diagnosed with the disease between the ages of 40 and 60 (again, coinciding with women’s menopausal years, when sex hormones plummet).
Gut Bacteria Plays a Role
Don’t freak out, but you have up to three pounds of microbes, and as many as 1,000 species, living in your GI tract. While most of them are healthy bacteria that fight disease, some may actually trigger it. In fact, an out-of-whack gut microbiome has been linked with autoimmune diseases like RA and some researchers even suggest that changes in the bacteria that naturally hang out inside your gut (due to poor diet and antibiotic overuse, for example) may be to blame for rising rates of the disease.
Here’s how it works: Your gut plays a big role in regulating your immune system, so changes to it may lead to an abnormal immune response. (Though to be fair, an abnormal immune response could also lead to changes in the gut—it’s the proverbial chicken or egg question.) If gut bacteria do contribute to RA, it could explain why some patients improve with changes to their diet.
Mouth Bacteria Could Matter More Than You Think
Growing research points to oral bacteria as a trigger for RA. For years, scientists have observed a link between gum disease and rheumatoid arthritis. More recently, they’ve identified a specific species of bacteria found in patients with periodontal disease that contains an enzyme known to be a preliminary indicator of RA. Possibly, periodontal infection is an early warning sign of the disease in some people.
Do Infections Play a Role in Rheumatoid Arthritis?
A number of RA cases begin within a few weeks of a viral or bacterial infection. That’s because when your body senses danger from an infection, it “switches on” the immune response to fight off the invader. In some people, this immune response may fail to “switch off” as it should, leading to autoimmune diseases like RA.
Airborne Toxins Could Up Your Risk
Pollution, a.k.a. various toxins and harmful airborne substances, has been implicated in the development of RA. For instance, breathing in the dust from the mineral silica, found in construction materials like asphalt, brick, and concrete, has been shown to damage the lungs and may increase the risk of RA. In one retrospective study of over 2,000 Swedish construction workers, those exposed to silica dust were more than twice as likely to develop RA—and the higher the exposure, the greater the risk.
Some researchers speculate that RA actually starts in the lungs. High exposure to lung irritants like silica and cigarette smoke can lead to an increase in citrullinated proteins, which may trigger the inflammatory process that leads to RA.
In fact, lung problems are linked to RA, and may co-occur with the disease. Some patients experience symptoms like coughing or shortness of breath even before the joints act up.
Stress Can Make Symptoms Worse
If you’re stressed to the max, your body knows it. RA often develops or gets worse following periods of emotional upset, suggesting stress may be a trigger for flares as well as onsets. RA sufferers can vouch for the connection: In one study, 86 percent of patients blamed their joint symptoms on stress.
The relationship between persistent stress and chronic inflammation goes beyond rheumatoid arthritis. Some research suggests that autoimmune diseases may be more common among those diagnosed with stress disorders such as PTSD.
Good news/bad news: To the extent you can control stress in your life, you may be able to lower your risk of RA, as well as your odds of a flare. Of course, getting rid of the 21st century’s version of a common cold is easier said than done. Plentiful sleep, deep breathing exercises, and mindful meditation are all solid starting points.
No matter what caused your RA, if you have it, you have to learn to cope. We've got all the details on RA treatment to help you do just that - check it out here.
Genes and RA risk. Best Practice & Research Clinical Rheumatology. (2017). “Genetic and environmental risk factors for rheumatoid arthritis.” doi.org/10.1016/j.berh.2017.08.003
Environmental factors and RA. National Rheumatoid Arthritis Society. (n.d.) “What Is the Cause of Rheumatoid Arthritis? Non-Genetic Factors.” nras.org.uk/what-is-the-cause-of-rheumatoid-arthritis-non-genetic-factors
Tobacco smoking. Arthritis Care & Research. (2019). “Impact and timing of smoking cessation on reducing risk of rheumatoid arthritis among women in the nurses’ health studies.” doi.org/10.1002/acr.23837
Obesity and RA risk: Arthritis Care & Research. (2012). “Contribution of obesity to the rise in incidence of rheumatoid arthritis.” doi.org/10.1002/acr.21660
Gut microbiome mouse study: PLOS One. (2012). “Loss of sex and age driven differences in the gut microbiome characterize arthritis-susceptible mice but not arthritis-resistant mice.” doi.org/10.1371/journal.pone.0036095
Silica study: BMJ Open. (2017). “Risk of sarcoidosis and seropositive rheumatoid arthritis from occupational silica exposure in Swedish iron foundries: a retrospective cohort study.” dx.doi.org/10.1136/bmjopen-2017-016839