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Rheumatoid arthritis is an autoimmune, inflammatory disorder caused by a person’s immune system mistakenly attacking and destroying healthy cells within the body. 

When rheumatoid arthritis is present, the body is perceiving its own tissues, joints, and organs as foreign invaders. The immune system then produces antibodies to attack these healthy cells.  

This disorder specifically targets joints and the tissues surrounding the joints (synovial tissue), which causes the joints and cartilage to become inflamed, swollen, and stiff.

Testing for Rheumatoid Arthritis:

A person who has rheumatoid arthritis is either seronegative or seropositive. Seropositive is diagnosed when blood tests return positive results (among other tests), and seronegative is diagnosed when blood tests return negative results (among other present signs and symptoms).

To diagnose rheumatoid arthritis (RA), a blood test that identifies the presence of RF (rheumatoid factor) and anti-cyclic citrullinated peptides (anti-CCP) is performed. (RF and CPP are the antibodies produced by the immune system when it’s working in overdrive, attacking the body’s healthy tissues—which is what happens when RA is present.)

If this blood test comes back positive for RF and anti-CCP, this indicates seropositive rheumatoid arthritis. If these tests come back negative, but the patient is experiencing the signs and symptoms of rheumatoid arthritis, this is considered ‘seronegative rheumatoid arthritis’.  (An estimated 20% of RA patients are seronegative.)

Although, either test (RF or anti-CCP) can still come back as positive when RA is not present. This is when your rheumatologist may order X-rays and perform physical exams to assess your joints and identify the signs of RA.

What is the difference between rheumatoid arthritis and seronegative rheumatoid arthritis? 

The difference lies in the blood test results. When a person’s blood test results are positive for anti-CCP or RF, or both, this is a good indication of rheumatoid arthritis. When the results show negative for both anti-CCP and RF, but the person still exhibits multiple signs and symptoms of rheumatoid arthritis, this is a good indication of seronegative rheumatoid arthritis. 

“Seronegative” simply means the person does not have the same antibodies that a person who is “seropositive” has. A seronegative person may have such low levels of RF or anti-CCP in the body that a blood test does not detect the presence of either. 

As rheumatoid arthritis progresses further, levels of anti-CCP and RF can increase, which would change the diagnosis from seronegative rheumatoid arthritis to seropositive rheumatoid arthritis.  

Additionally, there are other common types of arthritis to be aware of. Osteoarthritis is known as the “wear-and-tear” arthritis, but impacts your body differently. There are distinct differences between osteoarthritis vs. rheumatoid arthritis. Then, there is also psoriatic arthritis, which is a chronic inflammatory disease that impacts the skin and joints. There are signs of psoriatic arthritis to look out for, like red, inflamed patches of skin.

How is seronegative rheumatoid arthritis diagnosed?

Seronegative rheumatoid arthritis is diagnosed through a series of tests, including blood tests, X-rays, and physical examinations. 

Blood tests aren’t always accurate, because every person is different, so the level of antibodies that each person possesses is likely to differ. The antibody count also depends on the severity of the disorder. In early RA, antibodies are produced at a much slower rate than in the more progressed stages of RA. Some tests won’t pick up on these low levels of antibodies and will return negative results.

To diagnose seronegative rheumatoid arthritis, a rheumatoid factor (RF) test and an anti-cyclic citrullinated peptides (anti-CCP) test are performed on the blood. If these tests show positive results, X-rays and physical examinations are also completed to accurately diagnose RA. (RA is difficult to diagnose because many of the signs and symptoms are similar to those of other diseases.) 

If these blood tests show negative results, X-rays and physical examinations are still performed, because seronegative RA could still be present. If X-ray results show inflamed or damaged joints, and a physical examination indicates numerous symptoms of RA, a person will be diagnosed with seronegative RA. 

These are some of the common signs and symptoms that your rheumatologist will look for when diagnosing seronegative RA: 

  • Joint pain
  • Joint stiffness (especially the joints in the hands, knees, elbows, ankles, hips, and feet)
  • Joint swelling
  • Joint redness
  • Joints that are warm to the touch
  • Persistent inflammation
  • Morning stiffness
  • Muscle fatigue
  • Eye redness 
  • Eye dryness

The main criteria your rheumatologist will follow when diagnosing seronegative rheumatoid arthritis include:

  • Negative blood test results for RF and anti-CCP
  • Symmetrical symptoms (a person experiences pain on both the left and right sides)
  • Polyarthritic symptoms (multiple joints are affected at once due to RA being a systemic disorder)
  • Condition is inflammatory

Risk Factors of Seronegative Rheumatoid Arthritis

There are numerous factors that may put you at a higher risk of developing seronegative rheumatoid arthritis:

  • Genetics and family history
  • Medical history (previous infections or viruses)
  • Smoking
  • Exposure to certain chemicals, minerals, and air pollutants
  • Sex (70% of people with RA are women)
  • Age (RA is commonly found in people between the ages of 40 and 60)

Seronegative RA and seropositive RA share most of the same risk factors. Although, studies have shown that obesity and smoking have a considerable impact on the development of seronegative RA. 

Genetics play a major role in the type of RA that a person develops. (Variations in human leukocyte antigen (HLA) genes are commonly seen in people who have seronegative and seropositive RA, as well as psoriatic arthritis. Variations in single nucleotide polymorphism (SNP) genes are also known to increase a person’s risk of developing seronegative RA.)

Treatment of Seronegative Rheumatoid Arthritis

Just like seropositive rheumatoid arthritis, seronegative rheumatoid arthritis cannot be reversed. 

Treatment of this disorder is focused on alleviating pain and discomfort associated with inflammation around the body. Treatment can also slow the progression of this disease, or stop the progression altogether. 

It’s important to listen to your body and be aware of the signs and symptoms of RA, because the earlier we can detect this disorder, the greater our chances are of slowing its progression. Seronegative RA causes serious damage to the joints and bones because the body attacks the synovial tissues that cushion the bones. When the synovial tissue and supporting cartilage deteriorate, the bones no longer have the padding they need, and they start to rub against each other, which deteriorates the bones over time.


The symptoms of seronegative rheumatoid arthritis can be treated with NSAIDs medications, like ibuprofen. NSAIDs are nonsteroidal anti-inflammatory drugs that reduce inflammation and alleviate pain associated with joint swelling. These medications can increase range of motion, as they reduce the swelling that causes stiffness and inhibits movement.

Other medications, specifically disease-modifying antirheumatic drugs (DMARDs), can be taken to slow joint damage caused by seronegative RA. Sulfasalazine is a common DMARD used to slow the progression of seronegative RA and psoriatic arthritis. 

Intra-articular Injections

Intra-articular injections of corticosteroids, hyaluronic acid, BOTOX®, and platelet-rich plasma (PRP) can be effective methods for reducing inflammation in the affected joints. These injections can also relieve pain and improve physical function. 

Herbal Remedies

There are a number of herbal remedies known to reduce the symptoms of seronegative rheumatoid arthritis and help patients to manage this disorder. Supplements that include evening primrose, fish oil, frankincense, rose hips, turmeric, probiotics, or glucosamine can help to ease affected joints and improve range of motion.

Be sure to talk to your rheumatologist before adding any supplements to your diet, though. These ingredients could cause side effects or adverse reactions when mixed with medications. 


Physical therapy can be an incredibly valuable treatment method for patients with seronegative RA. Because this disorder causes a decreased range of motion due to joint inflammation and cartilage deterioration, physical therapy can help to regain mobility by teaching patients new ways of moving their bodies to complete daily activities. 

Studies show that completing therapy “more than doubled the likelihood that patients with seronegative rheumatoid arthritis would respond to treatment with disease-modifying antirheumatic drugs (DMARDs)”.

Healthy Lifestyle Habits

No supplement, injection, or medication can benefit you quite like a healthy lifestyle can. Maintaining a healthy lifestyle can actually prevent this disorder from developing in the first place. 

Regular exercise is critical for keeping your joints in motion and building the necessary strength to support proper mobility. Exercise is also important for maintaining a healthy weight, which reduces your chances of developing or progressing this disorder. 

A nutrient-dense diet filled with whole grains, fruits, spices (specifically ginger and turmeric), and fatty acids can lessen or prevent inflammation and support a strong immune system.


If seronegative RA progresses to its later stages, there is an increased risk of damage to the joints and cartilage. In these cases, reconstructive surgeries or joint replacement surgeries may be necessary measures to restore physical function and reduce pain. 

Your rheumatologist will discuss your surgical treatment options with you if this method proves to be the best option for your condition. 

No matter which treatment method you and your rheumatologist decide is best for you, treating seronegative RA before it progresses and causes serious damage to the body is critical. The longer this disorder goes untreated or undetected, the more damage is done and the more intense the required treatment method may be. 

When you visit our UCF Rheumatology Services department, we take a compassionate approach toward treating your condition and helping you manage its symptoms. We aim to create a personalized treatment plan that addresses your concerns, mitigates any unpleasant symptoms, and suits your lifestyle. 

Our rheumatologist, Dr. Maria Farooq, is trained and certified in performing musculoskeletal ultrasounds and ultrasound-guided injections to help bring her patient’s relief with minimal discomfort using precision techniques.

She is a member of the American College of Rheumatology and American College of Physicians and enjoys helping patients by identifying and diagnosing the cause of their symptoms and finding appropriate treatments that enhance their quality of life and alleviate symptoms.

Schedule your appointment with a top rheumatologist in Lake Nona, Orlando today!