Seronegative Rheumatoid Arthritis

What is Seronegative Rheumatoid arthritis?

Rheumatoid Arthritis (RA) is an autoimmune disease in which the body's immune system mistakenly destroys its tissues. In RA, the tissues, joints and organs of the body are perceived as foreign invaders. This leads to a situation in which the immune system produces antibodies to attack these cells. RA primarily affects the joints and surrounding tissues of the joint (synovial tissues), though it can also affect other body parts.

A blood test that detects rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) is used to determine whether someone has rheumatoid arthritis (RA).  The antibodies RF and anti-CCP are created when the immune system is overactive and attacking the body's healthy tissues. There are two types of RA: Seronegative RA and Seropositive RA.  If the blood tests come back negative for RF and anti-CCP, but the patient is experiencing the signs and symptoms of RA, this is known as ‘seronegative RA’. Research has shown that about 20% of RA patients are seronegative.1

What are the symptoms of seronegative rheumatoid arthritis?

A diagnosis of seronegative RA occurs when the patient exhibits a particular set of signs and symptoms. Since antibodies are absent in the blood, it makes it difficult to diagnose rheumatoid arthritis. Some of the specific signs and symptoms used to diagnose seronegative rheumatoid arthritis are:

  • Joint pain and stiffness, specifically in the limbs, knees, elbows and hips
  • Joint swelling, tenderness and redness2
  • 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
  • Redness in the eye

How serious is seronegative rheumatoid arthritis?

Due to the body’s attack on the synovial tissues that cushion the bones, seronegative RA seriously harms the joints and bones. When the supporting cartilage and synovial tissue degrade, the bones lose the necessary cushioning and begin to rub against one another, thereby weakening them.2 Therefore, it is very important to detect this disorder at an early stage to have a chance of slowing its progression. This can be achieved by being aware of the signs and symptoms of RA.

Is seronegative arthritis the same as rheumatoid arthritis?

Seronegative RA shares most or all of its symptoms with seropositive RA but differs from the latter in that negative blood tests for anti-CCP and RF are found. A person who has seronegative RA could have such low levels of RF or anti-CCP in their body that a blood test does not detect their presence. The levels of anti-CCP and RF can increase as RA progresses, which would change the diagnosis from seronegative to seropositive RA.3

Is seronegative rheumatoid arthritis an autoimmune disease?

Yes, seronegative RA is an autoimmune disease characterised by synovial joint inflammation, which can cause irreversible cartilage damage, deformity, and functional disability.2      

How do you treat seronegative rheumatoid arthritis?

Seronegative RA cannot be cured, much like seropositive RA. The goal of the treatment for this condition is to reduce the pain and discomfort caused by the body's inflammatory processes. Treatment can also stop or significantly delay the progression of the disease. To slow the progression of RA, it is crucial to pay attention to your body and be aware of the warning signs and symptoms.  Seronegative RA can be treated by the following processes:


Nonsteroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen can be used to treat the symptoms of seronegative RA. These medications lessen swelling-related pain by reducing inflammation, as well as the oedema that causes stiffness and restricts movement.2  

Seronegative RA can impair joints and disease-modifying antirheumatic drugs (DMARDs), can be used to reduce this damage. A typical DMARD used to slow the course of seronegative RA is sulfasalazine. In severe cases in which DMARDs have failed, or an individual is intolerant to DMARDs, biological treatments like infliximab can be considered. Biological treatments work by preventing the immune system from attacking joints and bones.2 

Intra-Articular Injections

Intra-articular injections of corticosteroids, hyaluronic acid, botulinum toxin (Botox) and platelet-rich plasma (PRP) can effectively be used to relieve pain and improve physical function. These injections can also reduce inflammation in the affected joints.2

Herbal Remedies

The symptoms of seronegative RA can be reduced by several herbal remedies.4 The affected joints can be eased, and the range of motion improved with supplements that contain evening primrose, fish oil, frankincense, rose hips, turmeric, probiotics, or glucosamine. However, these ingredients could cause side effects or adverse reactions when mixed with other medications. Therefore, you must talk to your rheumatologist and pharmacist before adding any supplements to your diet.

Healthy Lifestyle Modifications

Maintaining a healthy lifestyle can prevent seronegative RA from occurring in the first instance. Physical activity helps maintain a healthy weight and decreases the risk of developing or the progression of the diseases as it keeps the joints in motion and builds the necessary strength to support proper mobility.5 A nutrient-dense diet can also assist by lessening or preventing inflammation and can result in a strong immune system.6


As there is a higher risk of joint and cartilage damage if seronegative RA develops to its later stages, joint replacement or reconstructive surgery may be required to restore physical function and relieve discomfort.7 If this course of action turns out to be the best choice for your situation, your rheumatologist will go over your surgical therapy options with you.

Other Important Factors about Seronegative Rheumatoid Arthritis you Need to Know

Several factors such as blood tests, patient medical history, physical examination and X-rays help in the diagnosis of seronegative RA. Therefore, no single blood test can accurately diagnose RA because some healthy people can test positive for anti-CCPs (false positive), while others who have RA might test negative (false negative). However, the presence of antibodies indicates RA together with damage to bones and cartilage on imaging tests, as well as swelling and joint pain.

Seronegative RA is more difficult to diagnose and takes longer for doctors to rule out other forms of arthritis such as psoriatic arthritis, gout, and spondyloarthritis, that aren't linked to high levels of anti-CCP.  According to some experts, seronegative RA remains an imprecise diagnosis, and in many cases, a diagnosis of seronegative RA is to be changed to seropositive. However, it is very rare to have a patient who is seronegative become seropositive.

Risk Factors for Seronegative Rheumatoid Arthritis

There are numerous factors that can predispose people to have rheumatoid arthritis. These factors are:

  • Age: Although RA can affect people at any age, it is typically seen in patients between the ages of 40 and 60. However, there are some instances of juvenile rheumatoid arthritis; therefore, clinicians need to be aware of this condition if a minor begins to exhibit symptoms of RA. 
  • Sex: Both men and women are vulnerable to RA, although women are much more likely to get the condition. Studies also show that approximately 70% of those affected by RA are women.9 This could be due to the presence of certain hormones in women that make them more susceptible to getting arthritis.7;9 
  • Environmental factors: Exposure to certain chemicals, viruses, bacteria, minerals, and air pollutants in combination with genetic factors can put people at high risk of developing seronegative RA.
  • Genetics and family history: Specific genes contribute to the emergence of RA. According to research, genetic markers such as a human leukocyte antigen (HLA), specifically HLA-DRB,1 increase a person's risk of developing rheumatoid arthritis. Also, there may be a greater risk of RA in people with a family history of the disease.8


Seronegative rheumatoid arthritis can be life-threatening. You must schedule an appointment with a doctor who can diagnose your signs and symptoms and confirm rheumatoid arthritis with a series of clinical tests. Early detection of RA and treatment can prevent or limit long-term damage to the joints and other parts of the body.


  1. Understanding Rheumatoid Arthritis Lab Test Results | HSS. Hospital for Special Surgery [Internet]. [cited 2022 Sep 26]. Available from:
  2. Seronegative RA: What are the Symptoms of Seronegative RA? - [Internet]. [cited 2022 Sep 26]. Available from:
  3. Linauskas A, Overvad K, Johansen MB, Stengaard-Pedersen K, Thurah A de. Positive predictive value of first-time rheumatoid arthritis diagnoses and their serological subtypes in the Danish National Patient Registry. CLEP [Internet]. 2018 [cited 2022 Sep 26]; 10:1709–20. Available from:
  4. Supplement and Herb Guide for Arthritis Symptoms | Arthritis Foundation [Internet]. [cited 2022 Sep 26]. Available from:
  5. Expert Tips on How to Have Lead an Active Lifestyle. UCF Health [Internet]. [cited 2022 Sep 26]. Available from:
  6. Vaccaro M. Nourishing Heart Healthy Snacks. UCF Health [Internet]. 2021 [cited 2022 Sep 26]. Available from:
  7. Seronegative Rheumatoid Arthritis. UCF Health [Internet]. [cited 2022 Sep 26]. Available from:
  8. Understanding Seronegative RA | Arthritis Foundation [Internet]. [cited 2022 Sep 26]. Available from:
  9. Let’s Dig Into Everything about RA - [Internet]. [cited 2022 Sep 26]. Available from:
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Habeebullah Oladipo

Bachelor of Science - B.Sc. Microbiology, University of Ilorin, Ilorin, Nigeria

Habeebullah is a Microbiologist and an early career researcher with keen interest in Infectious diseases,
Antimicrobial Resistance and global health.
He is currently undertaking his "Bachelor of Pharmacy" in University of Ilorin, Ilorin, Nigeria.

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