If You Have Rheumatoid Arthritis But Your Rheumatoid Factor Is Negative, What Does It Mean? (2023)

Rheumatoid arthritis (RA) is a chronic inflammatory condition that causes painful swelling of the joints. If it isn’t treated, over time the disease can permanently damage your joints and cause many other health issues. That’s why it’s important to diagnose and begin taking care of RA as soon as possible. Early intervention can prevent long-term disability and other life-altering complications.

If your doctor suspects you have RA, to begin the diagnostic process, they will take your personal and family medical history, perform a physical exam, and order a number of lab tests. One of those tests will be for an autoantibody called rheumatoid factor (RF).

Many people with RA will test positive for rheumatoid factor in their blood. When you test positive for rheumatoid factor — and/or another autoantibody called anti-cyclic citrullinated protein (anti-CCP) — you are considered to have “seropositive rheumatoid arthritis.”

Some people with RA will have negative rheumatoid factor and negative anti-CCP. These patients are considered to have “seronegative rheumatoid arthritis.” For these patients, confirming an RA diagnosis will depend on other criteria. What’s more, once you are diagnosed, it may mean a different disease course — as well as some complicated feelings about your condition.

Here’s what you need to know about rheumatoid arthritis with negative rheumatoid factor.

(Video) Rheumatoid Factor (RF); Rheumatoid Arthritis

The Connection Between Rheumatoid Factor and Rheumatoid Arthritis

Autoantibodies are proteins produced by your immune system. Rheumatoid factor is a kind of autoantibody.

When your rheumatoid factor levels are high, you may have an autoimmune disease, such as RA or Sjögren’s syndrome — or you may have another condition entirely. Among many other illnesses, elevated RF levels are associated with hepatitis C, leukemia, and endocarditis. Sometimes, even healthy older people have higher levels of rheumatoid factor.

Testing for rheumatoid factor can help diagnose RA, although it is just one part of a larger picture; there are many other criteria involved.

“Laboratory testing is confirmatory,” explainsJonathan Kay, MD, professor of medicine and population & quantitative health sciences and the Timothy S. and Elaine L. Peterson Chair in Rheumatology at the University of Massachusetts Medical School in Worcester. “It adds to the diagnosis, but by itself does not make the diagnosis of rheumatoid arthritis.”

When you are tested for rheumatoid factor, you will also be tested for anti-CCP (sometimes also called ACPA). Like the RF test, it does not confirm rheumatoid arthritis by itself, but helps to build a case for diagnosis.

What Does It Mean If My Rheumatoid Factor Is Negative?

While the percentage of people with seronegative RA has been estimated to be around 30 percent, a February 2020 study in theAnnals of Rheumatic Diseasessuggests that the trend has changed over the years, with more RA patients having the seronegative kind.

(Video) A Rheumatologist Explains: What to do with a +RF and neg CCP

Researchers found that between 40 and 60 percent of people diagnosed with rheumatoid arthritis test positive for rheumatoid factor. The rest of RA patients have negative rheumatoid factor. Along similar lines, about half of people who meet the criteria for RA test positive for anti-CCP. That means between about half of rheumatoid arthritis patients test negative for anti-CCP.

Though there are exceptions, people who have symptoms characteristic of rheumatoid arthritis and who test positive for anti-CCP will almost certainly be diagnosed with the disease. Unlike positive rheumatoid factor — which is present in a number of different conditions — anti-CCP is very specific to rheumatoid arthritis.

If you test positive for rheumatoid factor or anti-CCP and are diagnosed with rheumatoid arthritis, this is referred to as seropositive RA. If you have negative rheumatoid factor and negative anti-CCP and are diagnosed with rheumatoid arthritis, it is called seronegative RA.

Occasionally, seronegative RA patients may develop antibodies and become seropositive at a later date — but this does not occur in most cases.

What Is the Normal Range for Rheumatoid Factor?

Though there is some variation depending on the lab, a normal level of rheumatoid factor is typically considered to be less than 15 or 20 IU/mL.

A number above that is considered to be abnormal, and means you are positive for rheumatoid factor. Generally speaking, the higher the rheumatoid factor, the more severe your disease may be.

(Video) Rheumatoid factor positive test result: does that mean I have rheumatoid arthritis? Hatem Eleishi

Can You Still Have RA and Be Negative for Rheumatoid Factor?

If you have negative rheumatoid factor and test negative for anti-CCP, but other signs strongly point to RA, a rheumatologist can still diagnose you with rheumatoid arthritis. In this situation, Dr. Kay explains, “the diagnosis is based primarily on the patient’s description of their symptoms, their functional limitations — such as ability or inability to perform duties of daily living — and their physical examination revealing evidence of joint swelling and tenderness in a distribution characteristic of rheumatoid arthritis.”

Imaging can help confirm a diagnosis, as well. If joint erosion typical of rheumatoid arthritis shows up on an X-ray or ultrasound, it bolsters the case for RA.

Your doctor will also want to rule out the possibility of other disorders that may resemble RA. These conditions include, but are not limited to:

  • Psoriatic arthritis
  • Viral infections, such as parvovirus B19 or hepatitis B or C
  • Gout
  • Pseudogout

If, after satisfying these criteria, you are diagnosed with seronegative RA, your rheumatologist may revisit the diagnosis later on to make sure another condition doesn’t better fit your symptoms. For example, if you eventually develop scaly patches of skin called psoriatic plaques, you may actually have psoriatic arthritis instead of RA.

“You want to make sure there wasn’t a mislabeling or misdiagnosis,” explains Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University Schools of Medicine and Public Health and chief of rheumatology at Boston Medical Center. “Medicine isn’t black and white,” she adds. “Sometimes there’s some gray and we don’t necessarily always have a definitive answer.”

Understanding Rheumatoid Arthritis with Negative Rheumatoid Factor

Though there are many exceptions, it’s historically thought that seropositive RA patients are at risk for more severe disease with more complications than seronegative RA patients.

(Video) Diagnosis & Treatment Delay in Seronegative Rheumatoid Arthritis

“Traditionally it is said that seropositive rheumatoid arthritis has a more aggressive course with more joint destruction, formation of rheumatoid nodules, and perhaps more systemic involvement,” says Dr. Kay. “Traditionally, seronegative rheumatoid arthritis has had a less aggressive course.”

However, that does NOT mean that seronegative rheumatoid arthritis requires less serious treatment or attention. In fact, recent research has suggested that seronegative patients should be treated as aggressively as those who are seropositive.

Treatment for Rheumatoid Arthritis with Negative Rheumatoid Factor

Whether you have seropositive RA or seronegative RA, your rheumatologist will consider your individual situation when they develop your treatment plan. Your therapies will depend on your level of disease activity, your assessment of how you’re doing, and your physician’s assessment of how you’re doing, says Dr Neogi. “It is those types of assessments that guide therapy and when therapy needs to be escalated or changed,” she explains.

As for treatments themselves, there are very few differences in treatment options for seronegative RA patients — with some exceptions: rituximab (Rituxan). A biologic drug given via infusion, rituximab is prescribed to reduce symptoms when patients haven’t responded to other RA medications. “Analysis of clinical trials of rituximab have suggested that rituximab is less effective in patients who are seronegative,” says Dr. Kay. Similarly, the biologic medication abatacept (Orencia) might be more effective on seropositive RA patients than on those who are seronegative.

Most importantly, whatever your situation, it’s key to get an accurate diagnosis and start treatment in the first place. And the sooner you get started, the better off you’ll be, explains Dr. Kay. “With early initiation of effective therapy,” he says, “disease activity is often suppressed, regardless of the presence or absence or rheumatoid factor.”

Be a More Proactive Patient with ArthritisPower

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(Video) How is Rheumatoid Arthritis Diagnosed? | Johns Hopkins Rheumatology

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FAQs

Can I have rheumatoid arthritis with a negative RA factor? ›

Researchers found that between 40 and 60 percent of people diagnosed with rheumatoid arthritis test positive for rheumatoid factor. The rest of RA patients have negative rheumatoid factor.

What happens if RA factor is negative? ›

A low number (negative result) most often means you do not have rheumatoid arthritis or Sjögren syndrome.

Can you have rheumatoid arthritis with normal blood work? ›

Rheumatoid arthritis can be difficult to diagnose in its early stages because the early signs and symptoms mimic those of many other diseases. There is no one blood test or physical finding to confirm the diagnosis.

What can be misdiagnosed as rheumatoid arthritis? ›

People with inflammatory bowel disease (IBD) — including ulcerative colitis and Crohn's disease — may develop peripheral arthritis that affects the knuckles and can be mistaken for RA. IBD-related arthritis can also cause symptoms in the elbows, wrists, knees, and ankles.

What is the gold standard for diagnosing rheumatoid arthritis? ›

Radiographic imaging: the 'gold standard' for assessment of disease progression in rheumatoid arthritis.

Does rheumatoid arthritis always show up in blood tests? ›

No blood test can definitively prove or rule out a diagnosis of rheumatoid arthritis, but several tests can show indications of the condition. Some of the main blood tests used include: erythrocyte sedimentation rate (ESR) – which can help assess levels of inflammation in the body.

Is seronegative rheumatoid arthritis curable? ›

Doctors treat seronegative RA the same way they approach seropositive RA: Because there's no cure, the goal is to ease your symptoms and keep the condition from getting worse.

What is the normal range for rheumatoid arthritis? ›

Normal Results

Results are usually reported in one of two ways: Value, normal less than 15 IU/mL. Titer, normal less than 1:80 (1 to 80)

Can you have rheumatoid arthritis without inflammation? ›

In the early stages, people with RA may not see redness or swelling in the joints, but they may experience tenderness and pain.

How quickly does rheumatoid arthritis spread? ›

The symptoms of rheumatoid arthritis often develop gradually over several weeks, but some cases can progress quickly over a number of days. The symptoms vary from person to person. They may come and go, or change over time. You may experience flares when your condition deteriorates and your symptoms become worse.

How do I know if I have fibromyalgia or rheumatoid arthritis? ›

Rheumatoid arthritis causes visible damage to joints. Fibromyalgia does not. Rheumatoid arthritis also gets progressively worse, causing swelling and sometimes deformities. The pain from fibromyalgia is more widespread, while rheumatoid arthritis is concentrated initially to hands, wrists, knees and balls of the feet.

What triggers rheumatoid arthritis? ›

Rheumatoid arthritis is an autoimmune condition, which means it's caused by the immune system attacking healthy body tissue. However, it's not yet known what triggers this. Your immune system normally makes antibodies that attack bacteria and viruses, helping to fight infection.

Can you see rheumatoid arthritis on an MRI? ›

MRI can also detect signs of rheumatoid arthritis, but a doctor will also use a variety of other tests, such as blood tests. Doctors can distinguish between soft tissues and fluids using MRI. This means they can assess signs of rheumatoid arthritis, such as inflammation and the condition of the synovial membrane.

Where does rheumatoid arthritis usually start? ›

Early rheumatoid arthritis tends to affect your smaller joints first — particularly the joints that attach your fingers to your hands and your toes to your feet. As the disease progresses, symptoms often spread to the wrists, knees, ankles, elbows, hips and shoulders.

Do I have MS or rheumatoid arthritis? ›

The main difference between MS and RA is the area of the body affected by each. In RA, the joints are affected. In MS, there is damage to the central nervous system, which consists of the brain and spinal cord.

What is the most specific test for rheumatoid arthritis? ›

An anti-CCP antibody test — also called an ACCP test or CCP-test — looks for the presence of these antibodies to help confirm rheumatoid arthritis. An anti-CCP test can also help doctors determine the severity of a rheumatoid arthritis case.

What are the markers for rheumatoid arthritis? ›

The main clinically useful biologic markers in patients with RA include rheumatoid factors (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).

What are the inflammatory markers for rheumatoid arthritis? ›

The main clinically useful biologic markers for the diagnosis of rheumatoid arthritis (RA) are rheumatoid factors (RF) and antibodies to citrullinated peptides (ACPA) (see 'Rheumatoid factors' below and 'Anti-citrullinated peptide antibodies' below).

Which is worse osteoarthritis or rheumatoid arthritis? ›

The two conditions can cause similar symptoms, but they have different causes and treatments. OA usually affects fewer joints, and its symptoms are generally limited to the joints. The progression of RA is more difficult to predict, and it can cause more widespread symptoms.

What is the best prescription drug for arthritis? ›

Disease Modifying Anti-Rheumatic Drugs (DMARDs) act on the immune system to slow the progression and damage of rheumatoid arthritis. Methotrexate is the most commonly prescribed DMARD and the most effective. Plaquenil (hydroxychloroquine) is given for milder symptoms.

How does a rheumatologist diagnose rheumatoid arthritis? ›

Your rheumatologist will order blood tests and imaging tests. The blood tests look for inflammation and blood proteins (antibodies) that are signs of rheumatoid arthritis. These may include: Erythrocyte sedimentation rate (ESR) or “sed rate” confirms inflammation in your joints.

Is seronegative rheumatoid arthritis an autoimmune disease? ›

RA is an autoimmune disease. People with seronegative RA do not have high levels of the antibodies currently tested for in RA blood tests. However, as with seropositive RA, it responds to treatment that affects the immune system, suggesting it is an autoimmune disease.

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

The condition affects everyone differently, and symptoms can change over time. But one possible difference is that people who are seropositive commonly get firm lumps on or near their affected joints called rheumatoid arthritis nodules. People who are seronegative generally don't get these nodules.

How do I know if I have fibromyalgia or rheumatoid arthritis? ›

Rheumatoid arthritis causes visible damage to joints. Fibromyalgia does not. Rheumatoid arthritis also gets progressively worse, causing swelling and sometimes deformities. The pain from fibromyalgia is more widespread, while rheumatoid arthritis is concentrated initially to hands, wrists, knees and balls of the feet.

How do u know if you have rheumatoid arthritis? ›

Signs and symptoms of rheumatoid arthritis may include: Tender, warm, swollen joints. Joint stiffness that is usually worse in the mornings and after inactivity. Fatigue, fever and loss of appetite.

How fast does rheumatoid arthritis progress? ›

The symptoms of rheumatoid arthritis often develop gradually over several weeks, but some cases can progress quickly over a number of days. The symptoms vary from person to person. They may come and go, or change over time. You may experience flares when your condition deteriorates and your symptoms become worse.

What are the 3 types of rheumatoid arthritis? ›

Types of Rheumatoid Arthritis – Seropositive or Seronegative RA
  • Rheumatoid Factor Positive (Seropositive) RA. ...
  • Rheumatoid Factor Negative (Seronegative) RA. ...
  • Overlapping Conditions.
11 Feb 2016

Is inflammatory arthritis the same as rheumatoid arthritis? ›

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis. It tends to involve more than one of the small joints of the hands and feet. In particular, the lining of the joint or tendons (the synovium) is inflamed, causing warmth, pain, and stiffness.

What are the inflammatory markers for rheumatoid arthritis? ›

The main clinically useful biologic markers for the diagnosis of rheumatoid arthritis (RA) are rheumatoid factors (RF) and antibodies to citrullinated peptides (ACPA) (see 'Rheumatoid factors' below and 'Anti-citrullinated peptide antibodies' below).

What is the rarest form of arthritis? ›

Palindromic rheumatism (PR) is a rare type of inflammatory arthritis. Between attacks of joint pain and swelling, the symptoms disappear, and the affected joints go back to normal with no lasting damage.

Is rheumatoid arthritis a disability? ›

Is Rheumatoid Arthritis a Disability? Simply being diagnosed with rheumatoid arthritis does not qualify you for disability. However, if your ability to work is greatly affected or impaired by your condition, then with the proper documentation, you may be entitled to SSA disability benefits.

What is the new treatment for rheumatoid arthritis? ›

The newest drugs for the treatment of rheumatoid arthritis are the Janus kinase (JAK) inhibitors, which are FDA approved under the brand names Rinvoq, Olumiant, and Xeljanz.

Do your muscles hurt with rheumatoid arthritis? ›

Muscle weakness is a commonly reported symptom of rheumatoid arthritis. People with RA note tenderness, stiffness, and pain in affected muscles. RA can cause a 25% to 70% reduction in muscular strength, typically caused by decreased skeletal muscle mass.

What symptoms does a rheumatologist look for? ›

One reason is a family history of rheumatic or autoimmune disease. You may also make an appointment if you have symptoms of a condition they treat.
...
Symptoms of rheumatic disease include:
  • Dermatitis.
  • Dry eyes.
  • Dry mouth.
  • Fatigue.
  • Hair loss (alopecia).
  • Inflammation in the lining of the lungs.
  • Itching.
  • Muscle weakness.
30 Jan 2022

What is Stage 1 rheumatoid arthritis? ›

Many people feel joint pain, stiffness, or swelling. During stage 1, there's inflammation inside the joint. The tissue in the joint swells up. There's no damage to the bones, but the joint lining, called the synovium, is inflamed.

What triggers rheumatoid arthritis? ›

Rheumatoid arthritis is an autoimmune condition, which means it's caused by the immune system attacking healthy body tissue. However, it's not yet known what triggers this. Your immune system normally makes antibodies that attack bacteria and viruses, helping to fight infection.

Which is worse osteoarthritis or rheumatoid arthritis? ›

The two conditions can cause similar symptoms, but they have different causes and treatments. OA usually affects fewer joints, and its symptoms are generally limited to the joints. The progression of RA is more difficult to predict, and it can cause more widespread symptoms.

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