Rheumatoid Arthritis (Stahl, 2010) – Is rheumatoid arthritis genetic?

Old person hands, rheumatoid arthritis

Nebula Genomics DNA report for rheumatoid arthritis

Is rheumatoid arthritis genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

Sample report on rheumatoid arthritis from Nebula Genomics
Sample report on genetic variants from Nebula Genomics
To learn more about how Nebula Genomics reports genetic variants in the table above, check out the Nebula Research Library Tutorial.

Introduction (Part 1 of Is rheumatoid arthritis genetic?)

Rheumatoid arthritis is a long-term, persistent rheumatic disease and the most common inflammatory disease of the joints. The disease is often abbreviated RA. The condition is classified as an autoimmune disease, meaning that the body’s immune system attacks healthy cells by mistake, leading to symptomatic inflammation. In this case, antibodies attack the healthy lining of joints.

The onset of the disease is often gradual, but can also be sudden, with pain in the joints of the little fingers or toes. Other joints may also be affected, especially hand, knee, shoulder, foot, hip joints. Typically, the carpal bones, the metacarpophalangeal joints of the fingers, and the proximal interphalangeal joints (PIP) are preferentially affected. The finger end and toe end joints (distal interphalangeal joints, DIP) are not affected, unlike psoriatic arthritis. Such pain is caused when the lining of the joint becomes inflamed and the joint tissue is damaged.

A hand demonstrating signs of rheumatoid arthritis
A hand showing signs of rheumatoid arthritis. Wikipedia. CC-Attribution-Share Alike 3.0 Unported.

The affected joints swell, are overheated, and may appear red as a result. Patients also often experience joint deformity. Symmetrical synovitis of the truncal joints is typical. These symptoms are usually most pronounced in the morning causing what most patients describe as morning stiffness. As the disease progresses, more and more joints are affected.

The disease usually progresses in episodes which typically last between a few weeks and months. Between the individual relapses, the symptoms subside on their own. 

Is rheumatoid arthritis genetic?

Those who have a parent, sibling or offspring with the condition have a prevalence rate of 2 to 3%. On the other hand, the rates of the condition if one identical twin has the condition are as high as 15 to 20%. There are several genetic markers and over 100 regions in the genome known to be associated with the development of rheumatoid arthritis. Research continues to identify genetic components. 

HLA-DR4: Also called the major histocompatibility complex, MHC, this gene is most strongly associated with an increased risk of developing RA. Patients with this genetic variant also tend to have more severe symptoms.

STAT: This gene regulates and activates the immune system.

TRAF1 and C5: These genes play a major role in causing chronic inflammation.

PTPN22: This gene helps regulate signal transduction that controls the activity of immune system cells called T cells. It influences the progression and expression of a number of diseases, including rheumatoid arthritis. 

Epidemiology (Part 3 of Is rheumatoid arthritis genetic?)

Rheumatoid arthritis (RA) affects nearly 1% of adults worldwide. As of 2019, incidence of new cases ranged from 5 to 50 per 100 000 adults in developed countries, with risk increasing with age. That’s equivalent to about 1.5 million people in the United States. 

Rheumatoid arthritis affects women three times as much as men. Although individuals of any age can develop it, the average age of the condition is around 66 in the United States. Geographically, it is most prevalent in North America and Northern Europe. 

Causes (Part 4 of Is rheumatoid arthritis genetic?)

Rheumatoid arthritis occurs when the body’s immune system attacks the lining of joints, leading to inflammation. It is not certain what triggers this autoimmune reaction, but a genetic component most likely plays a role. There are also a number of environmental risk factors associated with the disease. For those predisposed to rheumatoid arthritis via genetics, the disease may be more easily triggered if exposed to external contributing factors such as bacteria, viruses, emotional stress, etc. 

Mayo Clinic lists some additional risk factors that may make individuals more susceptible to the disease:

  • Your sex. Women are more likely than men to develop the condition
  • Age. Rheumatoid arthritis can occur at any age, but it most commonly begins in middle age
  • Family history. If a member of your family has rheumatoid arthritis, you may have an increased risk of the disease
  • Smoking. Cigarette smoking increases your risk, especially if you have a genetic predisposition towards the condition. Smoking may also be associated with greater disease severity
  • Environmental exposures. Some exposures such as asbestos or silica may increase the risk. 
  • Obesity. People — especially women age 55 and younger — who are overweight or obese may be at a slightly higher risk 

Symptoms (Part 5 of Is rheumatoid arthritis genetic?)

In the early stages, people with rheumatoid arthritis may not see redness or swelling in the joints, but they may experience tenderness and pain. The effects of the condition normally begin in the smaller joints (those that attach the fingers to the hand for example) before expanding to the larger joints (knees, ankles, and shoulders). Rheumatoid arthritis usually occurs on both sides of the body. 

An x-ray of a knee
Rheumatoid arthritis of the knee. Flickr. MyArthritis.

Symptoms accompanying later stages of the disease include: 

  • Joint pain and swelling, tenderness, or stiffness that lasts for six weeks or longer.
  • Morning stiffness that lasts for 30 minutes or longer.
  • More than one joint is affected.
  • Small joints (wrists, certain joints in the hands and feet) are typically affected first.
  • The same joints on both sides of the body are affected.
  • Many people with RA get very tired (fatigue) and some may have a low-grade fever. RA symptoms may come and go. Having a lot of inflammation and other symptoms is called a flare. A flare can last for days or months. 

Rheumatoid arthritis is a chronic condition. Signs and symptoms appear periodically as a series of flares and remissions. The symptoms can lead to loss of function if severe enough. It may also affect non-joint parts of the body such as skin, eyes, heart, lungs, blood vessels, and bone. 

You should check with your doctor if you notice new signs and symptoms. 

It also increases your risk of developing other conditions such as osteoporosis, rheumatoid nodules (firm bumps of tissue), dry eyes and mouth (including Sjögren’s syndrome), infections, abnormal body composition, carpal tunnel syndrome, heart problems, lung disease, and lymphoma

Diagnosis (Part 6 of Is rheumatoid arthritis genetic?)

Rheumatoid arthritis can be difficult to diagnose in the early stages before the symptoms are more pronounced. There is no substitute for professional medical advice. During a physical examination, if you suspect you have rheumatoid arthritis, your doctor will most likely check your joints for swelling, redness and warmth. They may also check reflexes and muscle strength.

If your doctor suspects the presence of the condition, they will most likely refer you to a specialist called a rheumatologist. 

Blood tests

A person with rheumatoid arthritis will often have specific substances in their blood that are elevated compared to someone without the condition. For example, elevated erythrocyte sedimentation rate (ESR, or sed rate) signals too much inflammation in the joints. Elevated C-reactive protein (CRP) may indicate a non-specific inflammatory process. Other common blood tests look for rheumatoid factor (a blood protein) and anti-cyclic citrullinated peptide (anti-CCP) antibodies (pieces of protein). 

Imaging tests

These tests such as X-rays and MRIs are used to track the progression of the disease over time. Doctors will order these tests periodically to determine how much damage has occurred in the affected joints. 

An x-ray of rheumatoid arthritis in a shoulder
X-ray of rheumatoid arthritis of the shoulder. Wikipedia. CC-Attribution 3.0 Unported

Treatment (Part 7 of Is rheumatoid arthritis genetic?)

While there is no cure for rheumatoid arthritis, the symptoms can usually be managed through medication and therapy. If these approaches do not work, it may be possible to repair the joints through surgery.

Medications

NSAIDs: Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain and reduce inflammation. Some common non-prescription NSAIDs for RA include ibuprofen (Advil, Motrin IB) and naproxen sodium (Aleve). Your doctor may prescribe a stronger prescription NSAID. Side effects may consist of stomach irritation, heart problems and kidney damage.

Steroids: Corticosteroid medications reduce inflammation and pain and slow joint damage. Side effects may include thinning of bones, weight gain and diabetes. Steroids are generally not intended to act as a long term solution. Instead, they are often prescribed to relieve immediate symptoms and then substituted with a different treatment. 

Disease-modifying antirheumatic drugs (DMARDs): These drugs can slow the progression of rheumatoid arthritis and save the joints and other tissues from permanent damage. Side effects vary but may include liver damage, bone marrow suppression and severe lung infections.

Biologic agents: Also known as biologic response modifiers, this newer class of DMARDs. These drugs can target parts of the immune system that trigger inflammation that causes joint and tissue damage. These types of drugs also increase the risk of infections and blood clots in the lungs. Biologic DMARDs are usually most effective when paired with a nonbiologic DMARD, such as methotrexate.

Therapy

Physical or occupational therapy can help treat rheumatoid arthritis patients by giving them more flexibility of their affected joints through targeted exercise. Arthritis care may also include changes to daily routines or assistive devices that would reduce the reliance on those joints. For example, some companies make special gripping devices on everyday objects like knives for people with the condition. 

Surgery

Surgery may help restore your ability to use your joint. It can also reduce pain and improve function. It is usually only used as a final option when the effect of the condition cannot be successfully treated with medications.

Synovectomy: This surgery is performed to remove the inflamed lining of the joint (synovium). It is most common on larger joints such as the knees, elbows, wrists, fingers and hips.

Tendon repair: Inflammation and joint damage may cause tendons around your joint to loosen or rupture. This surgery is used to repair the tendons around your joint.

Joint fusion: Surgically fusing a joint can stabilize or realign a joint. It can also be used for pain relief when a joint replacement isn’t an option.

Total joint replacement: During joint replacement surgery, the surgeon removes the damaged parts of your joint and inserts a prosthesis made of metal and plastic.

More resources for patients and caregivers can be found on the American College of Rheumatology website. 

Osteoarthritis vs Rheumatoid Arthritis (Part 8 of Is rheumatoid arthritis genetic?)

Although these two conditions both affect the joints, they are very different types of arthritis. Rheumatoid arthritis is an autoimmune disorder that affects the whole body while osteoarthritis is a degenerative joint disorder that affects only joints if they’ve been damaged. 

Patients will often experience similar symptoms including stiff and painful joints, limited range of motion, tenderness and swelling at the affected joints, and increased feeling of symptoms in the morning. 

Differences between osteoarthritis and rheumatoid arthritis
Differences in joint structure. Wikipedia. CC-Attribution-Share Alike 3.0 Unported

Since rheumatoid arthritis is a broad autoimmune disorder, it also comes with symptoms that affect the whole body such as fever and muscle aches, as well as detrimental symptoms in the lungs, eyes, and heart. Patients with osteoarthritis lack these broad symptoms since the disorder is limited strictly to the joints. They tend to develop bone spurs, or excess bone growth at the edges of the affected joints.

Osteoarthritis is also less symmetrical than rheumatoid arthritis, sometimes affecting only one side of the body or affecting one side of the body more. Although there is no cure for either, treatments are available to manage the symptoms of both conditions. 

If you liked this article, you should check out our other posts in the Nebula Research Library!