Jennifer Freeman, MD

Doctor of Medicine (M.D.) in 2008 from UT Health San Antonio, Surgeon at TRACC Dallas

Oct 27, 2018 4 min read

Seronegative RA: What are the Symptoms of Seronegative RA?

Seronegative rheumatoid arthritis is the diagnosis of rheumatoid arthritis without the presence of certain antibodies in the patient’s blood. It is one of two main types of rheumatoid arthritis diagnoses.

Seronegative RA
In most cases of rheumatoid arthritis, the patient tests positive for rheumatoid factor (RF) and/or anti-citrullinated peptides (CPP) antibodies. These indicate that the patient is seropositive and that they possess the antibodies that cause an attack on joints and lead to inflammation. These patients tend to have a more severe disease course with more joint deformities, x-ray damage, disability and inflammation outside of the joints.

What is Seronegative Rheumatoid Arthritis?

When a patient tests negative for RF and anti-CCP antibodies, yet they still display strong symptoms consistent with rheumatoid arthritis, they are given a diagnosis of seronegative rheumatoid arthritis.

The term seronegative means they don’t possess the antibodies that seropositive patients do. In other words, seronegative patients may also simply possess extremely low levels of the antibodies – not enough for the test to detect.

Many seronegative rheumatoid arthritis patients go on to develop antibodies years after their initial diagnosis, which then changes their diagnosis to seropositive rheumatoid arthritis. This is one of the many reasons that a patient can still be diagnosed with rheumatoid arthritis even if they are seronegative.

Symptoms of Seronegative Rheumatoid Arthritis

Seronegative rheumatoid arthritis patients must possess a distinct set of symptoms in order to be diagnosed. This is because the lack of antibodies in the blood makes it more difficult to reach a rheumatoid arthritis diagnosis.

Some of the most important symptoms in diagnosing seronegative rheumatoid arthritis include:

  • Joint pain, stiffness specifically in the hands but also in knees, elbows, hips, feet and ankles
  • Joint swelling and redness
  • Joint tenderness
  • Symmetrical symptoms and in multiple joints
  • Ongoing inflammation
  • Morning stiffness lasting longer than 30 minutes
  • Fatigue
  • Eye redness

Though this is not an exhaustive list, the majority of these will support a rheumatoid arthritis diagnosis. If we compare these symptoms to seropositive rheumatoid arthritis symptoms, there are many similarities. However, many patients see these symptoms evolve and change over time.

It is thought that seropositive patients experience a more severe disease course than seronegative patients. But studies have also shown that in some patient cases, the progression is comparable and sometimes is there is little difference. This is where it becomes complicated in trying to classify rheumatoid arthritis into sub-types and to reach a solid diagnosis.

There are some symptoms that are thought to be rheumatoid arthritis in seronegative patients, but later turn out to be other conditions. These cases mainly involve differences in the types of joints and areas affected as well as the levels of inflammation.

How is Seronegative Rheumatoid Arthritis Diagnosed?

Once the blood tests rule out the presence of RF and anti-CPPs in the patient, it becomes more difficult to achieve a rheumatoid arthritis diagnosis. However, it does happen. Just as having the presence of antibodies doesn’t necessarily solidify a seropositive rheumatoid arthritis diagnosis, the absence of antibodies doesn’t necessarily rule out a rheumatoid arthritis diagnosis.

If a patient exhibits strong symptoms of rheumatoid arthritis (i.e. joint pain, inflammation, and symmetrical symptoms), x-rays can be performed to further examine the symptoms. If the x-ray results indicate bone and cartilage erosion and damage, then a rheumatoid arthritis diagnosis can be made.

Testing for levels of inflammation in a patient’s joints also helps to support a rheumatoid arthritis diagnosis in seronegative patients. Here are some important criteria doctors follow when diagnosing seronegative rheumatoid arthritis:

  • Negative antibody (RF, anti-CPP) blood test results
  • Symmetrical symptoms
  • Polyarthritic symptoms, meaning multiple joints are affected
  • Condition is inflammatory

Other Conditions Associated with Seronegative Patients

A seronegative result along with what are thought to be rheumatoid arthritis symptoms could potentially indicate other conditions altogether. Often times when inflammation is present or consistent it means that the seronegative patient may have osteoarthritis instead of rheumatoid arthritis. This is a common confusion.

Spondyloarthritis conditions are sometimes associated with seronegative rheumatoid arthritis because they are inflammatory. These are conditions like ankylosing spondylitis, reactive arthritis, as well as psoriatic arthritis.

Seronegative Rheumatoid Arthritis Prognosis

Determining a prognosis or outcome for any rheumatoid arthritis patient is difficult. Seronegative patients are no different. The disease itself may start out with mild symptoms and involve into more severe symptoms that make treatment more difficult.

Seronegative patients are often regarded as having a milder set of symptoms compared to seropositive patients. Generally, seronegative patients don’t develop rheumatoid nodules, which are commonly displayed in seropositive patients. This is never a certainty, however, and each patient’s individual symptoms and disease progression will differ.

Seronegative Rheumatoid Arthritis Treatment

Treatments for seronegative rheumatoid arthritis patients are approached the same way as seropositive patients. The goal of treatment is to mitigate pain and prevent the disease’s progression. Focusing on reducing pressure and deterioration of joints is very important in delaying the disease. Treatment should be started as early as possible to prevent the disease from worsening.

Medication & Herbal Remedies

It’s possible to treat symptoms of seronegative rheumatoid arthritis with medication. Ibuprofen and other nonsteroidal anti-inflammatory (NSAIDs) medications are recommended to decrease inflammation, especially during flare-ups.

Seronegative patients may also take methotrexate and other disease modifying antirheumatic drugs (DMARDs), like sulfasalazine, when anti-inflammatory drugs are not sufficient. In addition, intra-articular (in the joint) steroidal injections are also used to lower inflammation in that specific joint. Many patients find a significant reduction in pain and swelling with the use of effective home herbal remedies. In some cases, the symptoms are completely put into remission especially when taken in conjunction  with a customized auto-immune diet.

Common herbal recommendations include fish oil, evening primrose, turmeric, and boswellia. Each has the potential to interact with your current medications, and should be discussed with your doctor when creating your treatment plan.


Physical therapy is a positive way of supporting joint mobility and joint health. Physiotherapists and occupational therapists work with patients to help improve mobility and range of motion as well as reduce pain. These specialists can help implement new ways of performing daily activities to alleviate strain on joints.

Home Care

Maintaining an exercise routine is crucial for anyone with rheumatoid arthritis. Exercise helps improve mobility and build muscle strength. Reducing stress levels through meditation and relaxation exercises are also strongly suggested as a regular practice for all patients.


Reconstructive surgery and joint replacement surgery is necessary in some cases. Like with any surgery, there is always a risk. A decision to pursue surgery should be made with your team of physicians. Sometimes surgery can improve quality of life and reduce pain.