Nature vs Nurture - The causes of rheumatoid arthritis and why some people are more at risk

Chances are, you probably know at least one person living with chronic arthritis. And while this fact may seem unremarkable at first glance, the steady increase in arthritis cases across the globe is truly a source of growing concern. Arthritis has become such a systemic problem around the world — so widespread, in fact, that it is currently estimated that 1 in 3 adults between the ages of 18-64 has or will have arthritis in their lifetime.¹

As one of the common types of chronic arthritis, rheumatoid arthritis (commonly referred to as RA) is actually an autoimmune disease. Unlike osteoarthritis that is caused by thinning of the cartilage between the joints, RA is caused by immune cells attacking and damaging healthy cells within the body. People living with RA experience significant inflammation and pain, primarily in the tissues surrounding their joints.²

While we search for ways to better treat this disease, researchers are also working hard to identify what causes the development of RA in the first place. Like other diseases, rheumatoid arthritis can be caused by a variety of different individual factors. From lifestyle choices to predetermined genetic dispositions, there is a wide range of possible risk factors that can increase the likelihood of someone experiencing RA.

So as it currently stands, it seems that we do not fully understand why certain people are at a higher risk for developing this disease. In the age-old argument for nature vs nurture, it seems like developing arthritis might be a combination deal.

What is rheumatoid arthritis?

While RA may present itself with similar symptoms of other types of joint-based arthritis, it is an autoimmune disease. Like all other autoimmune conditions, the immune system of a person with RA becomes hyperactive, attacking healthy and functional cells within the body. Unlike osteoarthritis that is caused by the breakdown of cartilage tissue inside of joints, RA is caused by the immune system attacking and damaging the tissues that surround the joints.¹

Left untreated, RA will result in chronic inflammation, pain, joint instability, and a loss of range of motion.

Because rheumatoid arthritis is a systemic disease (meaning that it impacts the entire body), the joints are not the only areas affected. Capable of attacking and damaging other cells, the most common non-joint related symptoms of RA include:³

• Cognitive impairments such as brain fog and lack of focus

• Increased risk for experiencing depression and other mental illnesses

• Dry eyes, eye infections, and increased risk for glaucoma

• Limited production of saliva

• Difficulty breathing, lung tissue scarring, and the development of nodules in the lungs

• Anaemia, hardened/restricted arteries, and the increased risk of heart attack

• Digestive issues including stomach ulcers and constipation

• Skin rashes

• Damage and weakening of the bones, osteoporosis

Additional Statistics about RA:

• In 2007, it was estimated that over 1.5 million people worldwide were suffering from rheumatoid arthritis. This number has only increased over the past decade.¹

• Women are 2-3 times more likely to be diagnosed with RA than men.¹

• The earliest identified cases of rheumatoid arthritis to date are 3500-5000-year-old skeletons found in Alabama.⁴ The skeletons have deformities that are consistent with the chronic symptoms of rheumatoid arthritis, indicating that this disease has plagued humanity for longer than we initially believed.

• Rheumatoid arthritis is one of the more common autoimmune conditions in the world. Impacting up to 860 out of 100,000 people, the number of RA cases is higher than other autoimmune conditions such as psoriasis, type I diabetes, Crohn’s disease, multiple sclerosis, and lupus.⁵

Risk factors for developing RA

Despite its prevalence and long-term presence in human history, modern researchers still have not been able to conclusively prove what causes rheumatoid arthritis. With multiple different factors playing a role in developing the disease, researchers are working hard to distinguish why some people are more likely to develop RA than others.

Some of the most commonly considered risk factors for rheumatoid arthritis include:⁶

Genetic predisposition

Our genetics play a major role in who we are as individuals. A gene, which is a unit of heredity passed along from our parents, is a specific and distinct grouping of small nucleotide proteins. Found in our chromosomes, genes are made from our DNA. While most genes are the same in all people (over 99%), differences in a small number of our genes result in our individuality.⁷ These differences are the reason why people have individual physical appearances — but they can also be a reason why some people are at a higher risk of developing certain diseases.

Minor variations in over a dozen genes have been analyzed by researchers looking to find a cause for rheumatoid arthritis. The most conclusive evidence of genetic involvement in the disease has been found in a variation in genes that code for immune system function like the HLA-DRB1 gene.⁸

The proteins created by this gene are used by the immune system to help identify body cells from harmful bacteria and viruses, so it is proposed that variations in this gene could be responsible for the development of many autoimmune disorders.⁸

Environmental factors

Where we live has more of an impact on our lives than just the scenery it provides. As many new research studies are showing the connection between air quality, pollution, and environmental chemicals, and the development of a wide variety of health conditions, rheumatoid arthritis is a popular disease to study.

In densely populated urban areas like major cities, air pollution is becoming an increasingly large threat to human health. Recent studies have shown that people living in areas near large air pollution emission sources like factories, chemical plants, and urban centres, are at a higher risk of developing RA.⁹ Additionally, excessive exposure to irritating pollutant particles has been noted to lead to increased inflammation throughout the body, which in turn leads to increased severity of RA symptoms in those already diagnosed with the disease.

Another common source of chemical irritants in the modern world is our increased use of pesticides and insecticides. Used in many of the large commercial crops grown around the world, these chemicals have been created to target and kill common pests that can damage the yield of a crop. Now mass-produced and sprayed onto our produce, research has shown that exposure to chemical insecticides can increase a person’s risk of developing rheumatoid arthritis and other autoimmune disorders.¹⁰ Unfortunately, these chemicals seem to have an increased impact on women, who are already at an increased risk of developing RA.¹⁰

Hormonal fluctuations

Women are at higher risk for developing RA — why is that?

As chemical messengers constantly flowing throughout our bodies, our hormones have a huge impact on our overall health and wellness. Estrogen, the female sex hormone that plays an important role in female reproductive health, seems to have a couple of extra important services it provides as well — one of which, is protection against rheumatoid arthritis.

Research has shown that the female hormones of estrogen and progesterone offer additional protection and support to the joints of the body.¹¹ Beginning to rise during puberty, estrogen levels are the highest in women who are of childbearing age (and when they are menstruating). With age, these hormone levels drop, starting the phases of menopause.

When a woman's estrogen levels are low, it has been shown that they are more likely to experience a more severe flare-up of symptoms of rheumatoid arthritis.¹² It is believed that these hormonal changes play a role in the increased prevalence of rheumatoid arthritis diagnosed in women over men.

Lifestyle habits

Finally, another common risk factor for rheumatoid arthritis is actually something more within our own individual control. Our lifestyle habits (including what we eat, drink, and how we spend our time) have a major impact on our overall health and the likelihood of developing a disease.

A commonly discussed lifestyle habit that increases the risk of developing RA is smoking tobacco products. Damaging our fragile lung tissues and leading to increased amounts of inflammation throughout the body, smoking has a profoundly negative effect on our health. In recent studies, it has been found that heavy smokers (those who have smoked daily for 20 years) exhibit a significantly higher risk of developing rheumatoid arthritis.¹³ Additionally, those who smoke are less likely to respond strongly to common rheumatoid arthritis treatments, making their disease more severe than non-smokers.¹³

Other factors like diet, exercise level, sleep schedule, stress levels, previous infections and injuries, and access to modern medical treatments also play a huge role in the development and management of rheumatoid arthritis.

Lower-income people have it worse

With all of these risk factors considered and combined, some individuals are naturally at a higher risk of developing rheumatoid arthritis than others. And while these are steps that can be taken by every person to reduce the future risk of experiencing RA, unfortunately, social factors such as socioeconomic status, income, and education often get in the way of many people getting the preventative care they need.

Poverty has a direct impact on a person’s RA symptoms by:

• Increasing the time it takes to get the medical care they need. People of lower incomes are less likely to go to the doctor regularly, resulting in delayed diagnosis and more severe symptoms from chronically untreated diseases.

• Impacting their ability to seek out medical attention at the start of symptoms. Especially in places like the United States where medical care is heavily reliant on insurance coverage, many people living under the poverty line are unable to afford the care they need to treat RA.

• Increasing the likelihood of missing symptoms. Without access to specialist services such as rheumatologists, occupational therapists, and physiotherapists, people living in poverty are more likely to be forced into living with severe RA symptoms.

So as the number of people diagnosed with rheumatoid arthritis continues to rise year by year, identifying risk factors and promoting increased preventative care are essential steps that must be taken to reduce the future burden on our healthcare system. But how can we begin to tackle such a large problem?

The global fight against RA

As the treatment options for autoimmune diseases continue to become more refined and effective, there is hope on the horizon for those already living with rheumatoid arthritis. While historically people have relied heavily on pain medications like opioids to mask the pain of the disease, newer modern treatment options such as non-steroidal anti-inflammatories (NSAIDs), steroids, and disease-modifying antirheumatic drugs (DMARDs) are now the gold standard of treatment.¹⁴ Capable of actually tackling and reducing the symptoms of RA, these medications have been incredibly helpful and effective for people living with rheumatoid arthritis.

But as the projections for arthritis cases around the world continue to climb, preventative and self-care measures need to be added into the treatment plan in order to reduce the number of severe disease flare-ups presenting to local hospital emergency rooms.

As a way to increase public awareness and education about arthritis care and prevention, the CDC created a campaign called “Strive for Five.” Designed to be a helpful guide for those living with or at risk of developing arthritis, the five preventative treatment suggestions made by the CDC include:¹⁵

• Being active — Moving your body is a great way to stay healthy and reduce your risk of developing arthritis. Capable of reducing chronic pain and increasing the range of motion of your joints, low-impact exercises like walking, yoga, and tai chi can help to better manage and prevent the development of rheumatoid arthritis.

• Managing your weight — Carrying excess weight on our joints can quickly result in damage and injury. Reducing your risk of experiencing stress-related injuries in your joints by maintaining a healthy body weight is a great way to keep your joints healthy and strong as you age.

• Talking to your doctor — If you begin to experience any of the common symptoms of arthritis, it is best to talk to your doctor as soon as possible. Early diagnosis of rheumatoid arthritis leads to earlier access to treatments and better health outcomes for patients.

• Protecting your joints — Avoiding activities that put your joints at risk of injury is important in the prevention of arthritis. Injuries to the joints cause inflammation and damage, which in turn increases your risk of developing rheumatoid arthritis in the future.

• Learning new self-management skills — For those with RA or at risk of developing arthritis, taking an educational workshop about self-management skills is a great way to stay on top of your health. Able to shed some light on the disease and offer actionable steps to staying healthy, finding ways to get educated about arthritis is one of the best ways to reduce your risk of developing this disease.

With these guidelines and resources in place, public health organizations like the CDC hope to not only help those living with RA, but also those who are at risk of developing it in the future. More research is needed to be done to better identify common risk factors and better treatment options in order for us to truly get a hold over the future burden of rheumatoid arthritis.

We may not currently know if rheumatoid arthritis is a result of nature vs. nurture — but, in time, the world’s leading researchers are hopeful to crack the case once and for all.

Sources:

1. Arthritis by the numbers | The Arthritis Foundation

2. Rheumatoid arthritis | Center for Disease Control and Prevention

3. How does RA impact affect different areas of the body? | Medical News Today

4. Symmetrical erosive peripheral polyarthritis in the Late Archaic Period of Alabama (1988)

5. RA Statistics | Rheumatoid Arthritis.net

6. Rheumatoid arthritis | The Mayo Clinic

7. What is a gene? | Medline Plus

8. Rheumatoid arthritis | Medline Plus

9. Air pollution as a determinant of rheumatoid arthritis (2019)

10. INSECTICIDE USE AND RISK OF RHEUMATOID ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS IN THE WOMEN’S HEALTH INITIATIVE OBSERVATIONAL STUDY (2013)

11. How do hormones affect RA? | Healthline

12. Do female hormones affect the onset or severity of rheumatoid arthritis? | Wiley Online Library

13. Study highlights smoking-rheumatoid arthritis link | The European Commission Cordis

14. Rheumatoid Arthritis by the Numbers: Facts, Statistics, and You | Healthline

15. Infographics | Center for Disease Control and Prevention

The author, Claire Bonneau, is a medical writer and certified trauma operating room nurse.