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Identifying Seronegative Rheumatoid Arthritis Symptoms

Posted on September 12, 2022
Medically reviewed by
Diane M. Horowitz, M.D.
Article written by
Simi Burn, PharmD

There are two main types of rheumatoid arthritis (RA) — seronegative and seropositive — and they cause similar symptoms. Seronegative RA, however, is less common and more difficult to diagnose. Becoming familiar with the symptoms of seronegative RA can be useful if you’re seeking a diagnosis for symptoms like joint pain.

​​Members of myRAteam have shared their experiences with seronegative RA. One member said, “I have every documented symptom of RA, including high inflammation markers and skin nodules. Still, because the RA blood test was negative, my medical provider insists it is osteoarthritis and won’t refer me to a rheumatologist.”

Like seropositive RA, seronegative RA is a progressive condition — disease activity and symptoms get worse over time. Read on to learn more about seronegative RA and its symptoms.

What Is Seronegative Rheumatoid Arthritis?

The main difference between seronegative and seropositive RA is in how they’re diagnosed. Seropositive RA can be diagnosed by testing for the presence of antibodies called anti-cyclic citrullinated peptides (anti-CCPs) and rheumatoid factor (RF) in the blood.

Seronegative RA, on the other hand, does not produce these antibodies, so it can’t be diagnosed with the same blood tests. Instead, doctors will take your medical history, do a physical examination, perform X-rays to assess joint damage, and record your symptoms. Blood tests for erythrocyte sedimentation rate and C-reactive protein can show if you’re experiencing higher-than-normal levels of inflammation.

An early diagnosis of RA is essential. The sooner a person starts treatment, the better their chances of preserving joint function and quality of life will be. Because seronegative RA can’t be diagnosed as easily as seropositive RA, the presence and severity of symptoms are important parts of making a diagnosis.

Some people with seronegative RA will develop RF or anti-CCP antibodies months to years later in the disease course.

Seronegative Rheumatoid Arthritis Symptoms

The symptoms of seronegative RA are similar to those of seropositive RA, affecting mainly the joints but sometimes also the skin, eyes, and overall health. However, more research is needed to better compare symptoms of seronegative and seropositive RA. Study results are mixed regarding differences between the two types in terms of severity, response to treatment, and prognosis.

Joint Symptoms

Joint symptoms that help diagnose seronegative RA include:

  • Swelling, redness, or tenderness
  • Pain or stiffness, especially in the hands, wrists, elbows, hips, knees, ankles, and feet
  • Symmetrical symptoms (affecting the same joints on both sides of the body) involving multiple joints
  • Morning stiffness that lasts longer than half an hour

These joint symptoms may be present in either seronegative or seropositive RA. If left untreated, RA can cause joint damage or deformity over time.

Skin Symptoms

Seronegative RA can also produce symptoms on the skin, although some — such as sun sensitivity, fragile skin, and easy bruising — are caused by medications rather than the RA itself.

Skin symptoms of RA include nodules (firm lumps under the skin) and vasculitis (blood vessel inflammation), which may cause a rash. However, people with seronegative RA may be less likely to have nodules and vasculitis than those with seropositive RA.

“I had a bad rash on my forearm,” one myRAteam member shared. “Then it moved to my upper arm/shoulder. Now it’s back, starting today. It first started about three months ago. It itches so badly. I try not to scratch, but it’s hard.”

Eye Symptoms

Both seronegative and seropositive RA may cause symptoms that affect the eyes. It’s thought that swelling and inflammation caused by RA can damage eye tissue.

One research study of 196 people with RA found an association between eye problems and detectable levels of anti-CCP antibodies (a sign of seropositive RA). However, people with seronegative RA may also experience eye symptoms. More studies must be done to determine if eye symptoms, including severity, differ between people with seropositive and seronegative RA.

Eye symptoms include:

  • Pain
  • Redness
  • Vision changes such as blurriness
  • Light sensitivity

In addition, RA is associated with eye conditions like dry eye syndrome, keratoconjunctivitis from Sjögren’s syndrome (reduced tear production), peripheral ulcerative keratitis (an inflammatory condition of the cornea), scleritis and episcleritis (affecting the white of the eye), and uveitis (inflammation inside the eye). Tell a doctor immediately if you experience any eye symptoms so you can be treated as soon as possible.

One myRAteam member shared, “For about one month, I’ve been experiencing throbbing pain behind my eyes. The left eye is worse. The left eye pain moves from my eye to my temple to the top of my head. I have also been experiencing broken blood vessels in my left eye.”

General Symptoms

Although both seronegative and seropositive RA primarily affect the joints, inflammation from RA can also cause general symptoms. Some symptoms occur because of chemicals that the body produces in response to inflammation, and others are a result of pain from RA.

General seronegative RA symptoms include:

  • Fatigue
  • Malaise (a general feeling of uneasiness with no obvious cause)
  • Weakness
  • Weight loss
  • Depression

One myRAteam member shared, “I am worried that I have seronegative RA. ​​I have all of the symptoms except for the redness. I’m in pain and fatigued all of the time.”

Seronegative Rheumatoid Arthritis Treatment

Starting treatment for seronegative RA as soon as possible can help reverse joint damage and prevent disease progression. Some evidence indicates that people with seronegative RA may respond better to treatment than do people with seropositive RA.

Treatment for both seronegative and seropositive RA includes the following medications:

  • Nonsteroidal anti-inflammatory drugs like ibuprofen (Advil) and naproxen (Aleve)
  • Disease-modifying antirheumatic drugs, including methotrexate and biologics
  • Corticosteroids like prednisone


One myRAteam member shared, “After many years of damage, the blood tests show nothing. They call it seronegative RA. We just go by the damage seen on imaging, which is frustrating. We have to stay ahead of the damage with these new biologics.”

Other treatments for RA include surgery, lifestyle changes such as dietary regimens, and natural or complementary therapies.

Talk To Your Doctor About Your Symptoms

Tell your doctor as soon as you notice symptoms that might be a sign of RA. The Arthritis Foundation recommends seeing a doctor for joint symptoms that last at least three days or occur several times each month.

People with seronegative RA often take longer to get diagnosed and start treatment. Give your doctor a detailed account of all your symptoms so that you can be diagnosed and treated more quickly.

Connect With Others Who Understand

On myRAteam, you’ll have access to the social network for people living with RA and their loved ones. Here, more than 196,000 members come together to ask questions, give advice, and share their stories with others who understand life with RA.

Are you living with seronegative RA? What are your symptoms, and how do you manage them? Start the conversation in the comments below or by posting on your Activities page.

All updates must be accompanied by text or a picture.
Diane M. Horowitz, M.D. is an internal medicine and rheumatology specialist. Review provided by VeriMed Healthcare Network. Learn more about her here.
Simi Burn, PharmD is a seasoned pharmacist with experience in long-term care, geriatrics, community pharmacy, management, herbal medicine, and holistic health.. Learn more about her here.

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