What Is Seronegative Rheumatoid Arthritis?

Reviewed on 2/18/2022

Rheumatoid arthritis (RA) is an autoimmune disease that attacks the body's joints and other parts of the body. Seronegative rheumatoid arthritis is a type of rheumatoid arthritis in which certain antibodies are not present in the blood (most cases of RA are seropositive — when antibodies are present in the blood).
Rheumatoid arthritis (RA) is an autoimmune disease that attacks the body's joints and other parts of the body. Seronegative rheumatoid arthritis is a type of rheumatoid arthritis in which certain antibodies are not present in the blood (most cases of RA are seropositive -- when antibodies are present in the blood).

Rheumatoid arthritis (RA) is an autoimmune disease, in which the body’s immune system mistakenly attacks its own tissues. In rheumatoid arthritis, the joints are primarily affected though it can affect other parts of the body. 

Seronegative rheumatoid arthritis is a type of rheumatoid arthritis in which certain antibodies are not present in the blood. Most cases of RA are seropositive, in which antibodies are present in the blood. 

Two blood tests used to diagnose rheumatoid arthritis include the rheumatoid factor (RF) assay and anti-cyclic citrullinated peptides (anti-CCP). When a patient has symptoms consistent with RA but tests negative for RF and anti-CCP antibodies, they are diagnosed with seronegative rheumatoid arthritis. These patients may have these antibodies in their blood, but at extremely low levels that are undetectable by the blood tests. Seronegative patients may develop antibodies later in the course of their illness. 

What Are the Signs and Symptoms of Seronegative Rheumatoid Arthritis?

Patients who have seronegative rheumatoid arthritis patients must experience a specific set of symptoms and signs in order to be diagnosed because the lack of antibodies in the blood makes it more difficult to reach a rheumatoid arthritis diagnosis.

Specific symptoms and signs used to diagnose seronegative rheumatoid arthritis include the following:

  • Joint pain and stiffness 
  • Specifically in the hands, but also in the knees, elbows, hips, feet, and ankles
  • Joint swelling and redness
  • Joint tenderness
  • Symptoms occur on both sides of the body (symmetrical) and in multiple joints
  • Chronic inflammation
  • Stiffness in the morning that lasts more than 30 minutes
  • Fatigue
  • Eye redness

Patients with seronegative rheumatoid arthritis may have other symptoms as well, but the above symptoms must be present in order for a diagnosis of seronegative rheumatoid arthritis to be made. 

What Causes Seronegative Rheumatoid Arthritis?

It is unknown what causes rheumatoid arthritis but it is thought that susceptibility factors and initiating factors may affect a person's risk of developing the condition: 

Susceptibility factors increase a person’s susceptibility to developing rheumatoid arthritis when exposed to risk factors that initiate the inflammatory process. Susceptibility factors include:

  • Age: middle-aged or older
  • Female sex: twice as likely as men to develop RA
  • Genetics: people with a relative who has RA have an increased risk of developing the condition

Initiating factors (triggers) increase the chances a susceptible person will develop the disease, such as:

QUESTION

The term arthritis refers to stiffness in the joints. See Answer

How Do Doctors Diagnose Seronegative Rheumatoid Arthritis?

Rheumatoid arthritis is diagnosed with a combination of clinical, laboratory, and imaging information. Patients with seronegative arthritis must present with a particular set of symptoms as outlined above, along with testing negative for RF and anti-CCP antibodies. 

The following laboratory studies are used to diagnose rheumatoid arthritis:

  • Rheumatoid factor (RF) assay 
  • This test will be negative in seronegative RA
  • Anti-cyclic citrullinated peptide (anti-CCP) and anti−mutated citrullinated vimentin assays 
  • This test will be negative in seronegative RA
  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP) level 
  • Complete blood count 
  • Antinuclear antibody assay (ANA)
  • HLA tissue typing
  • Lyme disease, to rule out Lyme as a cause for the symptoms
  • Uric acid, to rule out gout

Imaging studies used to diagnose rheumatoid arthritis include the following:

  • X-rays (first choice): Hands, wrists, knees, feet, elbows, shoulders, hips, cervical spine, and other joints as indicated 
  • When patients test negative for RF and anti-CCP antibodies, X-rays may show bone and cartilage erosion and damage, which can aid in a seronegative RA diagnosis
  • Magnetic resonance imaging (MRI): Primarily the cervical spine
  • Ultrasound of joints: Joints, as well as tendon sheaths, changes and degree of vascularization of the synovial membrane, and even erosions

Joint aspiration and analysis of synovial fluid may be indicated in some cases. 

What Is the Treatment for Seronegative Rheumatoid Arthritis?

Treatment for seronegative rheumatoid arthritis is the same as for seropositive rheumatoid arthritis. 

The following medications are used to treat rheumatoid arthritis:

Other medicines used to treat rheumatoid arthritis include the following:

The following are surgical treatments for rheumatoid arthritis:

  • Synovectomy 
  • Tenosynovectomy 
  • Tendon realignment 
  • Reconstructive surgery or arthroplasty 
  • Arthrodesis 

Other therapies for rheumatoid arthritis include the following:

  • Physical therapy and exercise 
  • Occupational therapy 
  • Heat and cold therapies 
  • Joint-protection education 
  • Orthotics and splints 
  • Adaptive equipment 
  • Energy-conservation education 

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Reviewed on 2/18/2022
References
Baker, Joshua F. "Patient education: Rheumatoid arthritis symptoms and diagnosis (Beyond the Basics)." UpToDate.com. Dec. 23, 2020. <https://www.uptodate.com/contents/rheumatoid-arthritis-symptoms-and-diagnosis-beyond-the-basics?search=rheumatoid%20arthritis&source=search_result&selectedTitle=5~150&usage_type=default&display_rank=5>.

Freeman, Jennifer. "Seronegative RA: What are the Symptoms of Seronegative RA?" RheumatoidArthritis.org. Oct. 27, 2018. <https://www.rheumatoidarthritis.org/ra/types/seronegative/>.

Smith, H. "Rheumatoid Arthritis (RA)." Medscape.com. Jan. 31, 2022.<https://emedicine.medscape.com/article/331715-overview>.

Venables, P.J.W. "Patient education: Rheumatoid arthritis treatment (Beyond the Basics)." UpToDate.com. Feb. 20, 2020. <https://www.uptodate.com/contents/rheumatoid-arthritis-treatment-beyond-the-basics?search=rheumatoid%20arthritis&topicRef=512&source=see_link>.

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