What Is Seronegative Rheumatoid Arthritis (RA)?

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Seronegative rheumatoid arthritis is diagnosed in people who have the signs and symptoms of rheumatoid arthritis (RA) but do not test positive for anti-cyclic citrullinated peptide antibody (anti-CCP) or rheumatoid factor (RF)—two antibodies (immune system proteins) that are typically present in the blood of someone with RA.

Rheumatoid arthritis is an autoimmune disease that affects the joints. People with RA experience pain, swelling, and stiffness in their wrists, hands, feet, knees, spine, elbows, shoulders, and jaw. Over time, RA can cause permanent damage to the joints, leading to joint deformities and difficulty with mobility.

In more severe cases, RA can affect other parts of the body outside of the joints, such as the heart, lungs, skin, and eyes. While people with seronegative RA both experience similar signs and symptoms of RA, there are differences.

This article explains seronegative rheumatoid arthritis symptoms, causes, diagnosis, and treatment.

Woman with gray hair at home feeling pain in hands and wrists

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Types of Rheumatoid Arthritis  

The two types of rheumatoid arthritis are seropositive RA and seronegative RA, as follows:

  • Seropositive RA, known as RA, indicates that a person with RA has positive blood results for anti-CCP and rheumatoid factor along with all the signs and symptoms of the disease.
  • Seronegative RA is called seronegative because of the negative results of these antibody blood tests that are typically done when healthcare providers diagnose RA.

What Are Seronegative Autoimmune Diseases?

In autoimmune diseases, the immune system mistakenly attacks a person's own cells and tissues. Seronegative autoimmune diseases lack the presence of autoantibodies. Autoantibodies are specific immune system proteins directed against a target found on a person's cells.

Most people with autoimmune diseases have autoantibodies that can be detected through blood tests. These autoantibodies play a role in the development of autoimmune diseases and are used to help healthcare providers with the diagnosis.

With seronegative autoimmune diseases, symptoms are present along with other markers of the disease. However, there is a lack of autoantibodies, which may make diagnosis more challenging.

Seronegative RA Symptoms

People with seronegative RA may have more severe symptoms than those with seropositive RA.

Symptoms of seronegative RA include but are not limited to:

  • Joint stiffness that lasts longer than 30 minutes
  • Joint pain
  • Joint tenderness, swelling, and warmth
  • Joint swelling that interferes with daily activities such as buttoning a shirt or opening a jar
  • Fatigue
  • Loss of appetite
  • Low-grade fever

Over time, RA can affect other parts of the body, causing symptoms such as:

  • Anemia (a low number of healthy red blood cells)
  • Neck pain
  • Scarring and inflammation of the lungs
  • Inflammation of the blood vessels, lining of the lungs, and heart


The exact cause of RA is unknown however, a combination of several factors may influence the development of the disease. Factors include:

  • Genes: Research into the gene(s) responsible for RA is ongoing. However, there is some evidence that certain genes responsible for immune system function may be to blame. RA also runs in families. People with first-degree relatives (a parent, sibling, or child) with RA are 3 times more likely to develop the disease.
  • Environment: Exposure to certain viruses, bacteria, chemicals, or inhalants, may all play a role in the development of RA.
  • Hormones: People assigned female at birth are more likely to develop RA. Pregnant people may go into remission and experience reduced symptoms, suggesting that sex hormones could also play a role in the disease.


There is no single test for RA. Diagnosis of seronegative RA is based on symptoms, a physical examination, blood tests, and imaging studies such as X-ray or magnetic resonance imaging (MRI).

Since RA can have similar symptoms to other types of arthritis and joint conditions, a healthcare provider looks at the whole picture to reach a diagnosis.

Your healthcare provider will conduct a physical exam and look at your joints and how you walk and move. They will also ask about symptoms and how they affect your daily life.

Blood tests for RF and anti-CCP antibodies can help with diagnosis. In the case of seronegative RA, these will not be measurable. People with seronegative RA typically need more clinical symptoms to receive a diagnosis since they will not have positive antibodies to help confirm the diagnosis.

MRIs and X-rays can provide images of affected joints to help with diagnosis. These images measure the amount of damage to joints and monitor the progression of the disease.


Treatment for RA depends on the symptoms and will be different for everyone. Treatment goals include reducing joint pain and inflammation, maintaining joint function and mobility, and preventing joint deformity and destruction.

Anti-Inflammatory Pain Medications

Common pain medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), like aspirin and Advil or Motrin (ibuprofen), are used as a first-line treatment to help reduce pain and inflammation.

Corticosteroids (stronger anti-inflammatory medications) may also be used. Because steroids carry the risk of more side effects, they are typically used for short periods of time at low doses.

Disease-Modifying Antirheumatic Drugs (DMARDs)

Disease-modifying antirheumatic drugs (DMARDs) are used to slow or stop the progression of RA. Methotrexate, an immunosuppressive drug that calms the immune system, is the most common medication prescribed for RA. Plaquenil (hydroxychloroquine) can also be used to treat RA long-term.

Biologic DMARDs may also be used to treat RA. These may be prescribed alongside other DMARDs or on their own. Common biologics for RA include Enbrel (etanercept), Humira (adalimumab), and Rituxan (rituximab).

Physical and Occupational Therapy

Physical therapy, along with other gentle muscle-strengthening exercises such as Pilates, yoga, and swimming, have been shown to help with maintaining mobility and relieving pain.

Occupational therapy can help with everyday tasks that may become difficult. You may need braces or assistive devices.


Surgery to replace or repair joints is used as a last resort to restore mobility and reduce pain in people whose RA has progressed.


While there is no cure for RA, there are treatment options to slow progression and reduce pain. Many people who are diagnosed early with RA and begin treatment reach remission (an absence of disease activity) or experience a reduction in symptoms and disease activity.

Is Seronegative RA Serious?

Seronegative RA can present with more severe symptoms. However, most people with seronegative RA have similar outcomes to people with seropositive RA once treated.


Symptoms of RA vary not just from person to person, but also throughout your time with the disease. Seeking the help of a specialist can help you cope with changes.

A physical therapist can create an exercise program that works for your levels of pain and mobility. An occupational therapist can teach you ways to modify your daily activities. If you have trouble opening jars or buttoning your shirts, they can give you tools to manage these tasks on your own.

You may need the support of family, friends, and others with RA (through support groups) to help you cope with the emotional and physical effects of having a chronic condition. Also, consider seeing a counselor or mental health professional if you have difficulty coping.


People with seronegative RA have the same symptoms of RA, but do not test positive for typical RA antibodies. Symptoms of seronegative RA may be more severe and include joint pain and stiffness, fatigue, and loss of appetite.

The exact cause of RA is unknown but is thought to be due to a combination of genetics, environment, and hormones. RA is treated with anti-inflammatory pain medications and disease-modifying antirheumatic drugs (DMARDs).

A Word From Verywell

Though seronegative RA does not present with typical antibodies and may take longer to diagnose, know that your symptoms are real and deserve to be acknowledged. Finding a healthcare provider who listens to your concerns and answers your questions can help you live well with the disease.

11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Rheumatoid arthritis.

  2. Choi S, Lee KH. Clinical management of seronegative and seropositive rheumatoid arthritis: A comparative studyPLoS One. 2018;13(4):e0195550. doi:10.1371/journal.pone.0195550

  3. Lenti MV, Rossi CM, Melazzini F, et al. Seronegative autoimmune diseases: a challenging diagnosisAutoimmun Rev. 2022;21(9):103143. doi:10.1016/j.autrev.2022.103143

  4. Paalanen K, Puolakka K, Nikiphorou E, Hannonen P, Sokka T. Is seronegative rheumatoid arthritis true rheumatoid arthritis? A nationwide cohort study. 2021;60(5):2493-2494]. Rheumatology (Oxford). 2021;60(5):2391-2395. doi:10.1093/rheumatology/keaa623

  5. Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapiesBone Res. 2018;6:15. doi:10.1038/s41413-018-0016-9

  6. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Rheumatoid arthritis: diagnosis, treatment and steps to take.

  7. Reed E, Hedström AK, Hansson M, et al. Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activityArthritis Res Ther. 2020;22(1):170. doi:10.1186/s13075-020-02191-2

  8. Bullock J, Rizvi SAA, Saleh AM, et al. Rheumatoid arthritis: a brief overview of the treatmentMed Princ Pract. 2018;27(6):501-507. doi:10.1159/000493390

  9. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritisArthritis Rheumatol. 2021;73(7):1108-1123. doi:10.1002/art.41752

  10. Arthritis Foundation. Best exercises for rheumatoid arthritis.

  11. Ajeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017;9(10):249-262. doi:10.1177/1759720X17720366