Rheumatoid arthritis (RA) is an autoimmune condition and type of inflammatory arthritis. It causes pain, swelling, and stiffness in the joints. There are several different types, including seronegative and seropositive RA.

Most people with RA have seropositive RA. This means that they have a substance known as anti-cyclic citrullinated peptide (anti-CCP) antibodies in their blood. They also have another antibody known as rheumatoid factor. A doctor can confirm a diagnosis of seropositive RA by testing for these antibodies.

People who have RA symptoms without these antibodies may receive a diagnosis of seronegative RA.

Some people with seronegative RA test positive for antibodies at a later date. If this occurs, the doctor will change their diagnosis to seropositive RA. Seronegative RA is less common than seropositive RA.

In this article, learn about the symptoms of seronegative RA and how it differs from seropositive RA.

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The symptoms of seronegative RA are similar to those of seropositive RA.

They include:

  • tenderness, swelling, and redness in the joints
  • stiffness, especially in the hands, knees, ankles, hips, and elbows
  • stiffness in the morning that lasts for longer than 30 minutes
  • persistent inflammation
  • symptoms that affect joints on both sides of the body
  • fatigue

In the early stages of the condition, these symptoms tend to affect the hands and feet. In time, however, they can start to affect other joints. The symptoms can also change over time.

It is unclear if having seronegative or seropositive RA affects the progression and outlook of RA symptoms.

An older study from 2013 found that people with seronegative RA were more likely to have partial remission than those with seropositive RA. Overall, progression and a poor prognosis were more likely in those with seropositive RA.

In 2018, some researchers found that people with seronegative RA tended to have higher levels of active disease at the time of diagnosis. However, imaging tests showed they had similar damage to people with seropositive RA.

Learn more about how the symptoms of RA affect women.

An autoimmune condition develops when the immune system mistakenly attacks healthy tissue in the body. In RA, it attacks the synovium or joint lining. This results in damage to cartilage, leading to joint pain and inflammation. In the long term, it can damage the cartilage, and the bone can start to wear away.

It is not clear exactly why this happens. However, some people with RA have anti-CCP antibodies and rheumatoid factor in their blood. These antibodies may play a role in inflammation. People with RA and antibodies will have a diagnosis of seropositive RA.

People with seronegative RA have the same symptoms and inflammation. However, they do not have these antibodies.

Experts are still investigating why this happens and what it means.

Risk factors

Some people appear to be more likely to develop a form of RA. The risk factors are similar for seropositive and seronegative RA and include:

  • genetic factors and family history
  • previous infection with certain bacteria and viruses
  • smoking or exposure to secondhand smoke
  • exposure to air pollution and certain chemicals and minerals
  • sex, as 70% of those with RA are women
  • age, as it mostly develops between the ages of 40 and 60 years
  • obesity

Some evidence suggests that a triggering event affecting the lungs or mouth, such as periodontal disease, may play a role in the development of RA.

Although the overall risk factors are the same for both types of RA, the authors of a 2018 study note that specific genetic features may lead to different types of RA.

Research also suggests that people with seronegative RA may be more likely to have high blood pressure.

Learn more about 10 risk factors for RA.

Diagnosing seronegative RA can be challenging.

A doctor will:

  • ask about symptoms
  • carry out a physical examination
  • run some tests, including blood tests

Blood tests for anti-CCPs and rheumatoid factor

Around 60–80% of people with RA have certain markers in their blood known as anti-CCPs.

They will also have another antibody, known as rheumatoid factor. However, rheumatoid factor can be present with other diseases, not only RA. Doctors usually test for both anti-CCPs and rheumatoid factor.

People with symptoms of RA and these antibodies will receive a diagnosis of seropositive RA.

For people with seronegative RA, a blood test will not show any sign of anti-CCPs or rheumatoid factor. This can make diagnosis more difficult.

If a person’s symptoms suggest the presence of RA, the doctor may diagnose RA, even if the individual does not have rheumatoid factor in their blood.

Learn more about blood tests for RA.

Other tests

Other tests can help diagnose seronegative RA, including imaging tests. An X-ray, for example, may detect erosion and damage to the bone and cartilage.

Controversy

According to the Arthritis Foundation (AF), there is some controversy about diagnosing seronegative RA.

They note, for example, that some people receive a different diagnosis at a later date, such as psoriatic arthritis or spondyloarthritis. This suggests they did not have RA to start with.

The AF also cites research in which further testing showed that people with a diagnosis of seronegative RA did, in fact, have the antibodies. However, the authors added that scientists do not agree on this.

Treatment for seronegative RA is similar to treatment for seropositive RA.

It will focus on slowing the progress of the condition, preventing joint damage, and relieving the symptoms.

Lowering overall inflammation levels and disease activity can also reduce the risk of complications, such as cardiovascular disease, in the future.

Treating the symptoms

Some options for relieving the symptoms of seronegative and seropositive RA include nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids.

NSAIDs can treat pain and swelling during flare-ups. However, they do not affect the course of the condition.

Steroids can help manage inflammation during flare-ups or when severe symptoms affect a specific joint. However, steroids can have adverse effects, so they are not suitable for regular use.

Learn more about steroids for RA.

Slowing the progress

Options for slowing the progress of the condition include biologic drugs and targeted therapy, known as disease-modifying antirheumatic drugs (DMARDs).

DMARDs can help slow the progress of RA by changing how the immune system works. Methotrexate (Rheumatrex) is one example of a DMARD. Targeted therapy, such as tofacitinib (Xeljanz), targets specific cells within the immune system.

If one drug does not help, a doctor may offer an alternative.

DMARDs do not offer pain relief. However, they can help reduce symptoms and preserve joints by blocking the inflammation that can slowly destroy the joint tissue in people with RA.

DMARDs can take time to make a difference. The doctor may prescribe NSAIDs or corticosteroids, meanwhile, to help with pain and inflammation.

Learn more about DMARDs and biologics for RA.

Surgery

Surgery can be an option for people with severe joint damage. Joint replacement surgery can help improve function and mobility and boost a person’s quality of life.

Learn if supplements can help lower inflammation.

AF suggests that certain foods may help manage the symptoms of RA. However, people should consult their doctor before adopting any special diets.

Foods to choose

Some people choose to follow an anti-inflammatory diet, which emphasizes plant-based foods.

Choices include:

  • fresh fruits and vegetables
  • nuts and seeds
  • lean meat
  • low fat dairy or dairy alternatives
  • whole grains

Omega-3 fatty acids appear to have anti-inflammatory properties and may ease pain and stiffness in tender joints. These come from fish oil. Therefore, eating cold-water fish such as herring, salmon, and tuna may help.

The Mediterranean diet may also help people with RA eat a healthful, well-balanced diet that includes the right amount of omega-3 fatty acids, fruits, vegetables, and whole grains.

Get a meal plan and 26 recipes for the anti-inflammatory diet here.

Foods to avoid

Omega-6 fatty acids are present in corn, safflower, soybean, and sunflower oils. Too much omega-6 can increase the risk of joint inflammation and obesity.

Other foods that may worsen inflammation include:

  • hamburgers, chicken, and meats grilled or fried at a high temperature
  • processed and fatty meats
  • processed foods and foods that are high in saturated fats
  • foods containing added sugar and salt

Smoking and alcohol

Smoking tobacco and drinking a lot of alcohol can also worsen the symptoms of RA.

People who smoke should see their doctor about quitting as soon as possible. Smoking can trigger RA and contribute to disease severity and progression.

Learn more about how alcohol can affect RA here.

Some natural remedies may help manage RA:

  • Stretching and gentle exercise: A doctor will advise on a plan. Water exercise and tai chi are helpful options.
  • Relaxation and mindfulness: Yoga, tai chi, and massage might help.
  • Heat and cold: Applying heat or ice packs covered with a towel may help relieve swelling and pain.
  • Rest: Getting a good night’s sleep can help. However, people should remain as active as possible during the day.
  • Supplements: Fish oil, turmeric, and probiotics may help. However, a person should ask their doctor before using any supplements. Some supplements, such as thunder god vine, may have serious side effects.
  • Acupuncture: People should ensure they find a qualified practitioner for acupuncture.

However, there is not yet enough evidence to support many natural remedies for RA. People should ask their doctor before starting a new treatment or making significant changes.

Learn more about natural remedies for RA.

Here are some questions people often ask about seronegative RA.

How is seronegative RA different from RA?

People with seronegative RA have the usual symptoms of RA. However, blood tests do not detect the antibodies known as anti-CCP and rheumatoid factor.

Is seronegative RA serious?

Whether seronegative or seropositive, RA is a serious disease that can lead to pain and inflammation in joints and throughout the body. Anyone with signs of RA should seek medical advice.

Is seronegative RA an autoimmune disease?

RA is an autoimmune disease. People with seronegative RA do not have high levels of the antibodies currently tested for in RA blood tests. However, as with seropositive RA, it responds to treatment that affects the immune system, suggesting it is an autoimmune disease.

People with seronegative RA have all the symptoms of RA. However, blood tests will show that they do not have anti-CCP antibodies or rheumatoid factor in their blood. Experts are still investigating why this happens.

The outlook for seronegative RA appears to be similar to that of seropositive RA. Sometimes, future blood tests show that rheumatoid factor has developed in a person’s blood over time.

A doctor will advise on the best treatment. However, lifestyle measures such as a healthful diet and regular activity can help manage symptoms.

Learn about the 10 best apps to support people with RA.

Read this article in Spanish.