Why Rheumatoid Arthritis Develops (2022)

Rheumatoid arthritis (RA) is caused by your immune system attacking parts of your own body as if they were dangerous germs. Among other tissues, the immune system targets membranes surrounding your joints, which are called the synovium. That leads to inflammation that can damage and even destroy the joints' bone and cartilage.

As in other autoimmune disorders, such as lupus and psoriasis, the underlying cause of rheumatoid arthritis is not well understood. What doctors do know is that certain factors—including smoking and obesity—can place you at higher risk of not only getting the disease, but having more severe symptoms.

Why Rheumatoid Arthritis Develops (1)

Common Causes

Rheumatoid arthritis, like all autoimmune diseases, is defined by an immune system that hasgone awry. Under normal circumstances, the body produces defensive proteins (called antibodies) that are "programmed" to target and attack a specific disease-causing agent (called an pathogen).

For reasons unknown, the body will sometimes produce autoantibodies ("auto" meaning "self") that mistake normal cells and tissues for pathogens. Depending on the disorder, the autoimmune assault may begeneralized (affecting multiple organs) or specific (preferentially targeting one or more organ systems).

With rheumatoid arthritis, the joints are specifically targeted, suggesting that a part of the immune system is "misprogramming" the antibodies in a very specific way. Variants in thehuman leukocyte antigen (HLA) system, the genetic site that controls the immune response, are believed to be at the center of this anomaly.

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

It is possible that a specific combination of gene variants and/or genetic mutations may be enough to trigger the disease. Even so, not all people with these gene variants develop rheumatoid arthritis, and not all people with rheumatoid arthritis have these gene variants.

(Video) Rheumatoid arthritis - causes, symptoms, diagnosis, treatment, pathology

That means it's likely other factors can trigger the autoimmune response, especially (but not only) a genetic predisposed to the disease. One theory is that certain bacteria or viruses may inadvertently "confuse" the immune system. Four infections suspected of triggering rheumatoid arthritis in some people are:

  • Epstein-Barr virus (EBV)
  • Escherichia coli (E. coli)
  • Hepatitis C virus (HCV)
  • Mycobacterium

Scientists believe that there may be cross-reactivity between these antigens and certain normal cells of the body. If so, antibodies produced in response to EBV, for example, may see EBV and a normal cell as the same thing. Even if the EBV infection eventually resolves, the body will remain on "high alert," ready to pounce on any cellit believes to be EBV.

Other factors may also cause the immune system to malfunction. Some of these factors may be modifiable, meaning we can change them, while others may not.

Non-Modifiable Risk Factors

Rheumatoid arthritis affects some groups of people more than others. The three non-modifiable factors commonly linked to the disease are:

  • Age
  • Gender
  • Family history of rheumatoid arthritis (genetics)


While rheumatoid arthritis can strike at any age, the onset of symptoms usually begins between the ages of 40 and 60. Moreover, the risk increases as you get older.

Overall, the odds of developing rheumatic arthritis will more than triple between the ages of 35 and 75, increasing from 29 new cases per 100,000 people per year to 99 new cases per 100,000 people per year, according to research from the Mayo Clinic.


Women are two to three times likely to get rheumatoid arthritis than men. While the explanation for this disparity is far from definitive, hormones are believed to play a role.

This is evidenced in part by research showing women often develop the disease after major shifts in their hormones. This sometimes happens immediately after pregnancy or with the onset of menopause. Estrogen, or specifically the depletion of estrogen, is believed to be the culprit.

Accordingly, estrogen replacement may offer a protective benefit to older women who may otherwise be vulnerable to the disease.

The same benefit may be extended to younger women who take a combination oral contraceptive (birth control pills). According to researchers at the Karolinska Institute in Stockholm, women who have used an estrogen-containing contraceptive for longer than seven years had a nearly 20% decreased risk of the most common type of rheumatoid arthritis compared to women who never took the pill.

(Video) Rheumatoid Arthritis Animation


If you have a parent or sibling with rheumatoid arthritis, your risk of developing the disease is three to five times greater than the general population. Having second-degree relatives with the disease more or less doubles your risk. These figures help illustrate the central role that genetics play in the development of the autoimmune disorder.

According to a 2016study published in The Lancet, between 40% and 60% of your risk of developing rheumatoid arthritis is genetic. While the exact genetic permutations have yet to be identified, people with autoimmune diseases are believed to have one or more mutations that alter the way their immune system recognizes and targets disease-causing agents.

One of the primary suspects is HLA-DR4, a gene variant linked to other autoimmune diseases, such as lupus, polymyalgia rheumatica, and autoimmune hepatitis. Research from the University of Michigan has further concluded that people with a specific genetic marker called the HLA shared epitope have a five-fold greater chance of developing rheumatoid arthritis than people without the marker.

Lifestyle Risk Factors

Lifestyle risk factors are those that are modifiable. Changing these factors may not only reduce the severity of your illness, but they may also even reduce your risk of getting the disease in the first place.


Smoking has a cause-and-effect relationship with rheumatoid arthritis. Not only do cigarettes increase your risk of getting the disease, they can accelerate the progression of your symptoms, sometimes severely.

A comprehensive review of clinical studies conducted by researchers at the Kobe University Graduate School of Medicine concluded that being a heavy smoker (defined as smoking a pack of cigarettes a day for more than 20 years) nearly doubles your risk of rheumatoid arthritis. The risk is greatly amplified if you also have the HLA shared epitope marker.

Moreover, smokers who test positive for rheumatoid factor (RF) are three times more likely to get rheumatoid arthritis than their non-smoking counterparts, whether they're current or past smokers. As its own independent risk factor, smoking is known to promote cell death, increase inflammation, and stimulate the production of free radicals that further damage already inflamed joint tissue.

If you take medications to treat the disease, smoking can interfere with their activity and make them less effective. This includes such foundational medications as methotrexate and newer TNF-blockers like Enbrel (etanercept) and Humira (adalimumab).

How to Successfully Complete a Smoking Cessation Program

(Video) Rheumatoid Arthritis | autoimmune disorder | Pathophysiology, risk factors ,treatment.


Rheumatoid arthritis is characterized by chronic inflammation that gradually degrades and destroys bone and joint tissue. Anything that adds to this inflammation will only make things worse.

Obesity is one condition that can trigger systemic inflammation, caused by the accumulation of adipose (fat) cells and the hyperproduction of inflammatory proteins known as cytokines. The more adipose cells you have in your body, the higher the concentration of certain cytokines. Moreover, increased body weight adds stress to the affected joints, particularly of the knees, hips, and feet, resulting in greater loss of mobility and pain.

Obesity can rob you of your ability to achieve remission, which is a state of low disease activity in which inflammation is more or less under control. According to research from the Weill Cornell Medical College, people with a body mass index (BMI) of over 30—the clinical definition of obesity—are 47% less like to achieve remission compared to people with a BMI under 25.

Physical and Emotional Stress

While rheumatoid arthritis symptoms can often flare up for no apparent reason, certain things may trigger a sudden worsening of symptoms.

Physical overexertion is one of these things. While the mechanism for this is poorly understood, it's believed that the sudden and excessive release of stress hormones, such as cortisol and adrenaline, may cause changes that indirectly intensify the autoimmune response. While this doesn't in any way undermine the enormous benefits of exercise in treating rheumatoid, it does suggest that physical activity needs to be appropriate, particularly insofar as the joints are concerned.

The body's response to physical stress may be mirrored by its response to emotional stress. While scientists have yet to find a clear association between stress and rheumatoid arthritis symptoms, people living with the disease often report that flare-ups come right after moments of extreme anxiety, depression, or fatigue.

Other common triggers include infections, including the cold or flu, which are associated with immune activation; and eating certain foods that trigger anallergic response in some people, causing the immune system to react abnormally.

All of these factors place varying degrees of stress on the body which the immune system responds to, sometimes adversely.

(Video) Why haven’t we cured arthritis? - Kaitlyn Sadtler and Heather J. Faust

Frequently Asked Questions

  • What are the symptoms of RA?

    Initial symptoms may not be obvious, but they can include an ache or slight pain, joint inflammation, warmth and redness around joints, fatigue, and low-grade fever. As the disease progresses, the joints deteriorate and there will be a decreased range of motion and eventually deformity in the affected joints.

  • What is the difference between rheumatoid arthritis and osteoarthritis?

    Rheumatoid arthritis and osteoarthritis have some overlapping symptoms, but they differ in that RA is caused by an abnormal immune system response and OA is caused by degeneration of joints over time. Osteoarthritis tends to start with a particular joint, while RA affects multiple joints, usually on both sides of the body.

How Rheumatoid Arthritis Is Diagnosed

(Video) Rheumatoid Arthritis - Signs & Symptoms | Johns Hopkins Medicine


How does rheumatoid arthritis develop? ›

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. This causes the thin layer of cells (synovium) covering your joints to become sore and inflamed, releasing chemicals that damage nearby: bones.

Why is rheumatoid arthritis a problem? ›

RA commonly affects joints in the hands, wrists, and knees. In a joint with RA, the lining of the joint becomes inflamed, causing damage to joint tissue. This tissue damage can cause long-lasting or chronic pain, unsteadiness (lack of balance), and deformity (misshapenness).

Why rheumatoid arthritis has no cure? ›

Ultimately, because of the avascular nature of cartilage, once damage has occurred, it cannot be repaired, thus making a cure essentially impossible. It appears that once the inflammatory rheumatoid synovial organ has formed in a specific joint, it is unlikely that this tissue can be brought back to 'normal'.

Why does rheumatoid arthritis occur in joints? ›

As the tissue that lines your joints (synovial membrane) becomes inflamed and thickened, fluid builds up and joints erode and degrade. Rheumatoid arthritis is a chronic inflammatory disorder that can affect more than just your joints.

How do you explain rheumatoid arthritis? ›

Describe your symptoms and how they may change, improve, or worsen. Help them understand how RA affects different parts of your body. Or that they may not see any outward signs of your disease. Let them know that you still may be dealing with pain, stiffness, and other issues that they may not see.

Can rheumatoid arthritis come on suddenly? ›

In a few people with RA -- about 5% to 10% -- the disease starts suddenly, and then they have no symptoms for many years, even decades. Symptoms that come and go. This happens to about 15% of people with rheumatoid arthritis. You may have periods of few or no problems that can last months between flare-ups.

Is rheumatoid arthritis a serious disease? ›

RA is a very serious autoimmune disease, in which your immune system mistakenly attacks your own body's tissues and causes severe joint pain, stiffness, severe fatigue, and sometimes deformity, usually in the hands, shoulders, knees, and/or feet.

Does rheumatoid arthritis go away? ›

Rheumatoid arthritis is a lifelong disease. When it's treated, it may go away for a little while, but it usually comes back. It's important to see your doctor as soon as symptoms begin. The earlier you start treatment, the better your outcome.

Can you live a normal life with rheumatoid arthritis? ›

80% of sufferers can lead a normal life with the aid of medication. In the past, rheumatoid arthritis meant being condemned to a wheelchair,” says arthritis expert Daniel Aletaha from the Department of Medicine III, (Division of Rheumatology).

Can vitamin D reverse rheumatoid arthritis? ›

With a vitamin D dose ≤50,000 IU, only serum vitamin D and TJC improved, and with a vitamin D dose> 50,000 IU, the VAS and DAS28 improved. Conclusions: Compared with placebo control interventions, vitamin D supplementation seemed to be an effective intervention for patients with rheumatoid arthritis.

Can you live with rheumatoid arthritis without medication? ›

You'll need to keep up with your usual medical care, but some natural remedies might help relieve pain and stiffness from rheumatoid arthritis (RA). Many of them are simple, like using heat and ice packs. Others, like acupuncture, need a trained pro.

How do you beat rheumatoid arthritis? ›

Slow, gentle, flowing exercises like Pilates, tai chi, and yoga help boost your balance and flexibility. They may even ease your pain. Research by the Arthritis Foundation shows that yoga poses, breathing, and relaxation lower joint tenderness and swelling for some people with RA.

Where does rheumatoid arthritis usually start? ›

The most commonly affected areas during the onset of RA are the small joints in your hands and feet. This is where you may first feel stiffness and an ache. It's also possible for RA inflammation to affect your knees and hips.

What bacteria causes rheumatoid arthritis? ›

The researchers found that 75% of people with new-onset, untreated rheumatoid arthritis had the bacterium Prevotella copri in their intestinal microbiome.

Can stress cause rheumatoid arthritis? ›

Rheumatoid arthritis (RA) is a chronic inflammatory joint condition and an autoimmune disease that can be caused by stress, according to research. Stress triggers rheumatoid arthritis by setting off the immune system's inflammatory response in which cytokines are released.

How fast does rheumatoid arthritis progress? ›

Clinical History. The typical case of rheumatoid arthritis begins insidiously, with the slow development of signs and symptoms over weeks to months. Often the patient first notices stiffness in one or more joints, usually accompanied by pain on movement and by tenderness in the joint.

Can you reverse rheumatoid arthritis? ›

Like other forms of arthritis, RA can't be reversed. Even if you show evidence of low inflammation and your joints aren't swollen and tender, your doctor may want you to continue taking some medication to avoid a flare of the disease. With the right combination of treatments, RA can go into remission.

Why do I suddenly have arthritis? ›

The most common triggers of an OA flare are overdoing an activity or trauma to the joint. Other triggers can include bone spurs, stress, repetitive motions, cold weather, a change in barometric pressure, an infection or weight gain. Psoriatic arthritis (PsA) is an inflammatory disease that affects the skin and joints.

How long does rheumatoid arthritis last? ›

The length of time an RA flare lasts can vary widely, from a few hours to several days or weeks. If a flare does not improve after 7 days, it may be a good idea to contact a physician.

Is RA a death sentence? ›

Overview. Share on Pinterest A person cannot die from RA, but the associated inflammation can lead to life-threatening complications. RA is a chronic medical condition that involves increased levels of inflammation in tissues throughout the body. A person cannot die from RA.

Is rheumatoid arthritis a big deal? ›

Having rheumatoid arthritis can lead to several other conditions that may cause additional symptoms and can sometimes be life threatening. Possible complications include: carpal tunnel syndrome. inflammation of other areas of the body (such as the lungs, heart and eyes)

What celebrities have RA? ›

Famous Faces With RA
  • 1 / 14. Glenn Frey. ...
  • 2 / 14. Lucille Ball. ...
  • 3 / 14. Tatum O'Neal. ...
  • 4 / 14. Christiaan Barnard. ...
  • 5 / 14. Kathleen Turner. ...
  • 6 / 14. Camryn Manheim. ...
  • 7 / 14. Aida Turturro. ...
  • 8 / 14. Seamus Mullen.
Oct 7, 2021

Has anyone cured their rheumatoid arthritis? ›

There is no cure for rheumatoid arthritis (RA), but remission can feel like it. Today, early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) and biologics makes remission more achievable than ever before.

What age does RA usually start? ›

You can get rheumatoid arthritis (RA) at any age, but it's most likely to show up between ages 30 and 50. When it starts between ages 60 and 65, it's called elderly-onset RA or late-onset RA. Elderly-onset RA is different from RA that starts in earlier years. It also comes with a separate set of treatment challenges.

How can I lower my rheumatoid factor? ›

Regular exercise is a great way to strengthen muscles and increase joint range of motion. Research from 2014 found that exercise may also improve sleep quality and fatigue in people with RA. Choose exercises that don't stress your joints. Brisk walking, swimming, and water aerobics are usually good low-impact choices.

Does rheumatoid arthritis hurt everyday? ›

1, 2004 -- Pain, stiffness, and fatigue affect 70% of rheumatoid arthritis patients every day despite treatment with the newer, more advanced drugs against the disease, according to a new Arthritis Foundation survey.

Does rheumatoid arthritis get better with rest? ›

Balancing activity with rest.

It's important to try to stay physically active even during a flare, but rest is also especially important when RA is active and joints feel painful, swollen or stiff. Rest helps reduce inflammation and fatigue that can come with a flare.

What is end stage rheumatoid arthritis? ›

End-stage rheumatoid arthritis (RA) is an advanced stage of disease in which there is severe joint damage and destruction in the absence of ongoing inflammation.

What deficiency causes rheumatoid arthritis? ›

Reduced vitamin D intake has been linked to increased susceptibility to the development of rheumatoid arthritis (RA) and vitamin D deficiency has been found to be associated with disease activity in patients with RA.

Is sun good for rheumatoid arthritis? ›

Living in a sunnier climate may reduce the risk of developing rheumatoid arthritis, according to US researchers. Their study of more than 200,000 women, published in the journal Annals of the Rheumatic Diseases, suggested a link between sunlight and the risk of developing the disease.

Is omega-3 good for rheumatoid arthritis? ›

Omega-3 fatty acids seem to prevent or attenuate experimental arthritis. They may have a beneficial effect in the treatment of rheumatoid arthritis. Clinical studies have shown that omega-3 fatty acids may have a modulatory effect on disease activity, namely on the number of swollen and tender joints.

Can rheumatoid arthritis burn itself out? ›

Synovitis is the main pathology and can lead to a progressive destruction of the joints. It is often said that RA "burns out", implying that the inflammation decreases spontaneously in the long term, mostly severe course of RA and reaches a stage with a stable absence of joint inflammation, even without treatment.

What is the safest treatment for rheumatoid arthritis? ›

Methotrexate is widely regarded as one of the safest of all arthritis drugs, though it carries some potential downsides. Gastrointestinal symptoms such as nausea and vomiting are its most frequent side effects.

What are usually the first signs of rheumatoid arthritis? ›

The early warning signs of RA include:
  • Fatigue. Before experiencing any other symptoms, a person with RA may feel extremely tired and lack energy. ...
  • Slight fever. Inflammation associated with RA may cause people to feel unwell and feverish. ...
  • Weight loss. ...
  • Stiffness. ...
  • Joint tenderness. ...
  • Joint pain. ...
  • Joint swelling. ...
  • Joint redness.

What are the 4 stages of rheumatoid arthritis? ›

The four stages of rheumatoid arthritis are known as synovitis, pannus, fibrous ankylosis, and bony ankylosis.
  • Stage I: Synovitis. During stage I, you may start having mild symptoms, including joint pain and joint stiffness. ...
  • Stage II: Pannus. ...
  • Stage III: Fibrous Ankylosis. ...
  • Stage IV: Bony Ankylosis.
Oct 12, 2021

Can rheumatoid arthritis go away? ›

Rheumatoid arthritis is a lifelong disease. When it's treated, it may go away for a little while, but it usually comes back. It's important to see your doctor as soon as symptoms begin. The earlier you start treatment, the better your outcome.

What is the life expectancy of a person with rheumatoid arthritis? ›

The average duration of disease were 10.5 years in male patients and 17.7 years in female. The average life span of the patients with RA, revealing 65.8 years in male and 63.7 years in female, were much shorter than of general population. The causes of all deaths were investigated by ourselves and/or autopsy.


1. Korean researchers develop new peptide to treat rheumatoid arthritis
(Arirang News)
2. Rheumatoid Arthritis (RA) Signs & Symptoms (& Associated Complications)
(JJ Medicine)
3. Arthritis Of The Fingers - Everything You Need To Know - Dr. Nabil Ebraheim
(nabil ebraheim)
4. International Team Creates Heart Disease Risk Tool Tailored to Rheumatoid Arthritis Patients
(Mayo Clinic)
5. My Rheumatoid Arthritis (RA) Story
(Swavy Curly Courtney)
6. Understanding Rheumatoid Arthritis Symptoms, Causes and Treatment | Dr. Rahul Jain ( Hindi )
(Narayana Health)

You might also like

Latest Posts

Article information

Author: Annamae Dooley

Last Updated: 07/24/2022

Views: 5340

Rating: 4.4 / 5 (65 voted)

Reviews: 80% of readers found this page helpful

Author information

Name: Annamae Dooley

Birthday: 2001-07-26

Address: 9687 Tambra Meadow, Bradleyhaven, TN 53219

Phone: +9316045904039

Job: Future Coordinator

Hobby: Archery, Couponing, Poi, Kite flying, Knitting, Rappelling, Baseball

Introduction: My name is Annamae Dooley, I am a witty, quaint, lovely, clever, rich, sparkling, powerful person who loves writing and wants to share my knowledge and understanding with you.