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, or rheumatoid factor, in their blood. A doctor can confirm a diagnosis of seropositive RA by testing for this substance.

When a person has RA without also having these antibodies, the condition is instead known as seronegative RA. People with seronegative RA may have other antibodies, or tests may show no sign of antibodies at all.

However, they may develop antibodies at a later stage in life. If this occurs, the doctor will change their diagnosis to seropositive RA. Seronegative RA is much less common than seropositive RA.

In this article, learn about the symptoms of and treatment options for seronegative RA.

a woman holding her knee because it is stiff from Seronegative RAShare on Pinterest
A person with seronegative RA may experience tenderness in the joints.

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.

Some experts suggest that the outlook for seronegative RA is better than it is for seropositive RA. This may indicate that seronegative RA is a milder form of RA.

For some people, however, the progression can be similar, and sometimes, a diagnosis will change to seropositive with time. It is also possible for a person with seronegative RA to receive a diagnosis for a different condition, such as osteoarthritis or psoriatic arthritis, later on in life.

A study found that people with seronegative RA were more likely to have a partial remission than those with seropositive RA, but overall, there was little difference in how the two types affected a person.

How do the symptoms of RA affect women? Find out here.

An autoimmune condition develops when the immune system mistakenly attacks healthy tissue in the body. In RA, it attacks the synovial fluid in the joints. 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.

Health professionals do not know exactly why this happens, but some people with RA have antibodies in their blood known as rheumatoid factor. This may play a role in the inflammation. However, not everybody with RA has this factor.

As mentioned above, people with seropositive RA will test positive for rheumatoid factor, but those with seronegative RA will not. Experts are still investigating why this happens and what it means.

There is also growing evidence to suggest that a triggering event that affects the lungs or mouth, such as periodontal disease, may play a role in the development of RA.

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 they 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

Although the overall risk factors are the same for both types of RA, the authors of a 2018 study note that obesity and smoking are more likely to be risk factors for seronegative RA, and that people seem to develop different types of RA depending on certain genetic features.

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

A doctor will ask a person about their symptoms, and they may also run some tests. However, a blood test for rheumatoid factor will be negative in a person with seronegative RA. 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.

In some cases, a doctor may recommend an X-ray, which may detect erosion and damage to the bone and cartilage.

Treatment for seronegative RA 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 lower the risk of experiencing cardiovascular disease in the future.

Treating the symptoms

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

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

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

Find out more about steroids for RA here.

Slowing the progress

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

DMARDs can help slow the progress of RA by changing how the immune system works. Methotrexate (Rheumatrex) is one example of a DMARD, but if one drug does not help, a doctor may offer an alternative. DMARDs do not offer pain relief, but 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 up to 2 months to make a difference. The doctor may prescribe NSAIDs or corticosteroids in the meantime to help with pain and inflammation.

If DMARDs do not help at all, a doctor may recommend targeted therapy, such as medications that work on the immune system in different ways. One example of this type of medication is tofacitinib (Xeljanz), which targets specific cells within the immune system.

Surgery

Many people with RA will never need surgery, but it can be an option for those who experience severe joint damage.

Undergoing joint replacement surgery can help improve function and mobility, which can boost a person’s quality of life.

Can supplements help lower inflammation? Find out here.

The Arthritis Foundation suggest that eating certain foods may help manage the symptoms of RA. However, people who have RA should consult their doctor before adopting any special diets.

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

Healthful 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.

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 tobacco and drinking a lot of alcohol can also make the symptoms of RA worse.

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.

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.

Apart from diet, some people suggest the following natural remedies for 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, but people should remain as active as possible during the day.
  • Supplements: Fish oil, turmeric, and probiotics may help, but 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 try to find a qualified practitioner.

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 any significant changes.

Get more detail on natural remedies for RA here.

People with seronegative RA have all the symptoms of RA, but blood tests will show that they do not have 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, but 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 here.

Q:

My blood test shows negative for rheumatoid factor, but I have the joint symptoms. Will my boss think I don’t have RA? Does it mean I don’t really have RA?

A:

Even if the rheumatoid factor test is negative, other autoantibodies may be present, especially cyclic citrullinated peptide antibody. However, even if both of these are absent, RA might still be the most appropriate diagnosis, so a negative antibody test does not rule out the condition. Incidentally, people should not need to mention their medical information to their boss.

Nancy Carteron, M.D., FACR Answers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.