Rheumatoid arthritis (RA) is marked by inflammation of the joints, causing pain and other symptoms.
If rheumatoid arthritis is left untreated, inflammation from the condition can start to develop in other areas of the body, causing various and sometimes serious complications that can affect other organs — such as the heart, lungs, eyes, and nerves — and could cause significant long-term disability. (1)
If you're experiencing rheumatoid arthritis symptoms, it's important to get diagnosed as soon as possible so that you can receive prompt treatment. For many people, functional disability — trouble with everyday routines, such as dressing, eating, and walking, caused by joint damage — often occurs one to two years before actual diagnosis. These issues may be a signal that you have RA.
There is no single test that can definitively diagnose RA.
As with other illnesses, diagnosis of RA typically begins with your doctor getting your medical history and conducting a physical exam.
You doctor will begin by asking questions about the symptoms you're experiencing, including when and how they occur, and how they've changed over time (if they have). One specific symptom she will ask about is morning joint stiffness that lasts for at least 30 minutes — a common RA symptom.
Morning stiffness is typically severe enough to interfere with physical functions after waking up, according to UpToDate, a physician-authored site.
The other main symptom is swelling of the joints that lasts for at least six weeks, particularly if the swelling occurs on the same joints on both sides of the body. Swelling that occurs for less than six weeks could be a sign of multiple different things; an example is acute viral polyarthritis, an inflammation of the joints caused by a virus.
Your doctor will also ask about any other medical conditions you have — people with RA frequently have co-occurring conditions, such as cardiovascular disease — and about those of your immediate family members, too.
During your physical exam, your doctor will look for signs of tenderness, swelling, warmth, and pain in your joints, and check to see if you have any movement limitations.
She will also check for rheumatoid nodules, or noticeable bumps that often occur at the base of arthritic joints, such as the elbows. (2) These nodules affect up to 30 percent of patients, according to research published in the journal Autoimmunity Reviews. (3)
Following those initial diagnostic procedures, your doctor will order blood tests. (1)
Rheumatoid arthritis is typically defined as being either "seropositive" or "seronegative," referring to the presence of specific antibodies in the blood. Rheumatic nodules occur almost exclusively in people with seropositive RA. (3,4)
Previously, patients were considered seropositive if they had the antibody rheumatoid factor, or RF. These antibodies are found in 70 to 80 percent of people with RA, but they're also found in 5 to 10 percent of people without RA, according to UpToDate. (2)
What's more, RF is also found in people with numerous other conditions, including some infections and other inflammatory conditions — so its presence doesn't specifically indicate RA.
Today, a more sensitive test for seropositivity is available. This test looks for anti-citrullinated protein antibodies (ACPAs), a collection of autoantibodies — antibodies that target and react to a person's own proteins, mistaking them as foreign. To detect ACPAs, the test looks for evidence of the antibodies' immune system reactivity with compounds called cyclic citrullinated peptides (CCPs), which are fragments of natural human proteins undergoing a certain type of molecular change. (5)
About 60 to 80 percent of people with RA have these so-called anti-CCPs, and these antibodies can show up years before symptoms develop, according to the Arthritis Foundation.
Compared with RF, anti-CCP is a more specific marker of the disease and high levels of anti-CCP antibodies may indicate a greater RA severity. (4)
In recent years, researchers have identified a number of different ACPAs, detected through the anti-CCP tests. A study published in June 2018 in the journal Annals of the Rheumatic Diseases found that no single ACPA is responsible for RA joint damage and inflammation.
Rather, having a number of different ACPAs is associated with a number of markers of joint destruction and inflammation, according to the study. This suggests that the anti-CCP tests may be able to help clinicians determine who will develop greater joint damage. (6)
Though RF and anti-CCP antibody tests are highly informative and can help with diagnoses, they're not enough to diagnose RA alone. Up to half of patients don't have both RF and anti-CCP antibodies when initially tested, and 20 percent of people who are found to have RA never test positive for the antibodies. (4,7,8)
Blood tests are not only used to detect RF and anti-CCP antibodies. They're also used to reveal if you have:
Like the antibody tests, these tests alone cannot diagnose RA. The ESR rate, for instance, is not specific to RA inflammation and can also be influenced by infections and age. And C-reactive protein, which is also not specific to RA, can be influenced by obesity and infection. (4)
Some patients still have RA but do not test positive for either anti-CCPs or RF — they have seronegative RA.
This form of RA is often more difficult to diagnose, and also usually produces milder symptoms than seropositive RA.
To diagnose seronegative RA, your doctor may conduct more tests to rule out other possible causes of your symptoms, such as osteoarthritis — which is sometimes misdiagnosed. Though osteoarthritis may produce similar symptoms to RA, osteoarthritis is a degenerative joint disease that develops from "wear and tear" instead of inflammation related to autoimmune issues. (5)
Your doctor may test your blood for infections, including human parvovirus B19, hepatitis B, hepatitis C, and Lyme disease. These issues can produce RA-like symptoms. She may also analyze the fluid within your joints to detect abnormalities and high white blood cell counts.
Your doctor may also conduct a synovial biopsy, which involves removing a small piece of the tissue lining one of your joints.
But even with these tests, a correct diagnosis of seronegative RA isn't guaranteed. The results of your joint fluid tests, for example, may instead indicate that you have gout. And your doctor may diagnose you with psoriatic arthritis if you later develop a skin rash.
Other diseases that may resemble seronegative RA include psoriatic arthritis, reactive arthritis, and ankylosing spondylitis, a form of chronic inflammatory arthritis that primarily affects the spine.
Some people are highly at risk of RA but don't yet have the condition — instead, they may have preclinical RA.
People with preclinical RA have the biomarkers (RA or anti-CCP) of RA but don't have the hallmark joint inflammation associated with the disease. Research suggests that tests can detect these biomarkers and autoantibodies three to five years before RA joint systems arise.
But that's not to say people with preclinical RA are free of health issues. They may have mild aches and pains, joint swelling on a single side of the body, or some nondescript fatigue or malaise, as well as a higher risk of heart attack or heart failure. (9)
For those with preclinical RA, disease-modifying anti-rheumatic drugs, which are used to treat RA, can significantly reduce RA risk, according to a meta-analysis published in August 2018 in the Annals of the Rheumatic Diseases. (10)
In the near future, physicians may be able to diagnose RA with a noninvasive procedure using infrared light.
In a pilot study published June 20, 2019, in the Journal of Biomedical Optics, researchers found that the technique, which involves placing a person's hand in an infrared scanner, can accurately detect markers of RA inflammation, such as lowered levels of blood oxygen and increased levels of blood content. (11)
But experts argue that the technique is not ready for clinical use, as it cannot make a definitive diagnosis of RA and cannot distinguish between different types of RA. (11)