What Is Seropositive Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is a lifelong autoimmune disease that primarily affects the joints. The most common type of RA is seropositive RA, where someone with RA has detectable anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) antibodies in their blood that can identify the disease.

High levels of one or both are associated with inflammation and increased disease severity. People with seronegative RA will not have detectable anti-CCP or RF levels.

Having seropositive RA doesn’t mean you should lose all hope. Many of the current treatment options can allow for people with RA—regardless of the type of RA they have—to slow down disease progression and enjoy a good quality of life. 

Bloodwork
Westend61/Getty Images.

RF and Anti-CCP Proteins

A significant number of people with RA are seropositive. The development of RA, its severity, and whether it is seropositive are dependent on rheumatoid factor and anti-CCP proteins. The percentage of people with RA who will test positive for rheumatoid factor is 70–90%.

RF is a protein antibody the immune system produces that go on to attack healthy tissues in the body, mainly the joints. High levels of RF tend to be associated with conditions like RA, but it is possible for RF to be detectable in healthy people and for people with RA to have normal levels of RF.

Anti-CCP is more sensitive and can show up many years before you even develop symptoms of RA. Much like RF proteins, they target healthy joints causing inflammation throughout the body. A comparative study reported in 2014 found anti-CCP antibodies in RA affected 87.2% of people with the condition.

Specific causes of RA are unknown although researchers speculate that RA is related to a combination of genetic and environmental factors. The heritability of seropositive RA is around 40 to 65%.

Seropositive RA Symptoms

RA has a specific set of symptoms associated with it, and these will come and go throughout your life. You will have periods where disease activity and symptoms are high­—called flare-ups—and periods of remission where you experience only a few or no symptoms.

Specific symptoms of RA may include:

  • Pain and swelling of joints, especially of the hands and feet
  • Several affected joints
  • Symmetrical joint pain—meaning the same joints on both sides of the body are affected
  • Stiffness in the morning that lasts 30 or more minutes
  • Deterioration of cartilage and bone shown on X-rays
  • Development of rheumatoid nodules—firm lumps under the skin near joints

Other symptoms of RA that are also seen in other autoimmune diseases and similar conditions include:

  • Fever
  • Chronic fatigue
  • Depression
  • Anemia
  • Muscle pain

The research shows people with seropositive RA tend to have more severe symptoms than those who are seronegative—although this doesn’t apply to everyone. Disease presentation and even treatment outcomes may not as positive as they would be for seronegative RA.

People with seropositive RA are more likely to develop complications of the disease, including rheumatoid vasculitis (inflammation of blood vessels), and rheumatoid lung disease. They also have a higher risk for comorbid conditions of RA, like cardiovascular disease and depression.

Seropositive vs. Seronegative

The number of people affected by RA in the United States is around 1.3 million people, according to the American College of Rheumatology. That number hasn’t really changed, but what has changed is the reduced number of people with seropositive RA.

A 2019 analysis out of the Mayo Clinic published in the journal Annals of the Rheumatic Diseases reports that from 1985 to 1994, only 12 out of every 100,000 people with RA were seronegative. And from 2005 to 2014, that number went up to 20 out of every 100,000 people.

People with seronegative RA will test negative for RF and anti-CCP proteins. They are diagnosed based on other criteria for RA like swollen joints and radiological joint changes.

A study published in 2016 by the journal Rheumatology finds that 38% percent of people diagnosed with RA are seronegative. Sometimes, people with seronegative RA will go on to be seropositive especially those with extremely low levels of RF or anti-CCP.

Many experts believe people with seropositive RA have more severe disease symptoms. However, a study published in 2015 by the journal BMC Musculoskeletal Disorders suggests the difference between seropositive and seronegative RA has more to do with affected joints than the severity of symptoms.

Here, researchers found seronegative RA could affect the wrists, ankles, and large joints while seropositive RA didn't cause the same destruction of these joints. Seropositive RA can still cause joint damage and disability, but seronegative RA seems to affect specific joints more often.

The researchers concluded that these findings highlight the importance of treating seronegative RA as aggressively as seropositive. They added that further study was needed to better understand the long-term outcomes of both types of RA.

A 2018 comparative study reported by PLoS One confirms the idea seronegative RA can cause more severe disease. Additionally, both seronegative and seropositive types may have similar radiographic damage.

The researchers also noted that people with seronegative RA have better responses to treatment than do people with seropositive RA, which might give some insight as to why they may have more severe disease.

Treatment

No matter what type of RA you have, your treatment options will be the same. Treatment will focus on managing pain and inflammation and preventing damage to joints. For both types of RA treatment includes a combination of medications, lifestyle changes, complementary therapies, and surgery.

Medication

Your doctor may prescribe one or more of the following medications to help manage your symptoms:

Lifestyle Changes

Lifestyle habits like diet and exercise can help you manage seropositive RA. Eating an anti-inflammatory diet can help you to reduce the number of RA flare-ups you have. A healthy diet can also reduce your risk for other diseases, especially those considered comorbidities of RA.

Exercise can help you to keep your joints mobile and build strength in your muscles. Ask your doctor about how you can safely incorporate exercise into your RA treatment plan.

It is also a good idea to not smoke with RA. Smoking is linked to more severe disease in RA and it can reduce the effectiveness of some of the treatments you take to manage RA. It is especially important for people with seropositive RA because they don’t respond as well to treatment—regardless of whether they smoke or not.

Complementary Therapies

Your doctor may suggest physical and occupational therapy to teach you exercises to help you keep your joints mobile and flexible. Your therapist may also suggest ways of doing daily tasks that don’t put as much pressure on your joints.

An occupational therapist can suggest assistive devices so that you are not stressing painful joints. This includes things like a cane, button hooks to help you with getting dressed, or a reacher to help you grab objects without having to reach.

Surgery

When medications fail to prevent or slow down damage to bones and joints, your doctor may suggest surgery. Surgery may help restore the ability to use a joint, reduce pain, and improve function.

A Word From Verywell

There is no cure for seropositive rheumatoid arthritis, but effective management of the disease means you can still enjoy a good quality of life. You should contact your doctor as soon as you start to experience symptoms of RA. Early diagnosis and treatment could potentially mean less joint disease and reduced disease progression.

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