Rheumatoid arthritis (RA) is a difficult disease for healthcare providers to diagnose, especially in its early stages, because the signs and symptoms are similar to those of many other conditions. So far, healthcare providers don’t have a single test that definitively diagnoses RA, so they rely a physical exam, family medical history, several blood tests, and imaging such as X-rays.

Rheumatoid arthritis differs from osteoarthritis (“wear-and-tear” arthritis) in that it is an autoimmune disorder. That means the immune system mistakenly attacks its own cells and tissues, primarily, in RA, the cells and tissues of the joints.

Most autoimmune diseases are hard to diagnose, but getting it right is important because it helps determine the appropriate course of treatment.

Physical Exam

One of the first tools of diagnosis is a physical exam. The aim of the evaluation is, in part, to determine the characteristics of the joint pain and swelling to better distinguish it from other causes of joint pain, like osteoarthritis.

Many of the questions your healthcare provider will ask are aimed at determining whether RA or osteoarthritis is more likely to be causing your symptoms.

In addition to evaluating your physical symptoms, the healthcare provider will review your family history. Rheumatoid arthritis can often run in families, doubling your risk of the disease if a second-degree relative (like a grandmother or uncle) has it and tripling your risk if an immediate family member (i.e., parent, sibling) is affected.

Labs and Tests

Lab tests are used for two primary purposes in diagnosing rheumatoid arthritis:

  • To classify your serostatusTo measure or monitor the level of inflammation in your body

Serostatus

Serostatus (loosely translated as “blood status”) refers to the key identifiers of the disease in your blood. If these compounds are detected in a blood test, you’re classified as seropositive. If they are not found, you’re deemed seronegative.

Seropositive results can be further classified as:

  • Low positiveModerate positiveHigh/strong positive

Two tests are used to establish your serostatus:

  • Rheumatoid Factor (RF): RF is a type of autoantibody found in approximately 70% of people living with the disease. Autoantibodies are proteins produced by the immune system that attack healthy cells or cell products as if they were germs. While high levels of RF are strongly suggestive of RA, they also can occur with other autoimmune diseases (such as lupus) or non-autoimmune disorders such as cancer and chronic infections.
  • Anti-Cyclic Citrullinated Peptide (anti-CCP): Anti-CCP is another autoantibody found in the majority of people with rheumatoid arthritis. Unlike RF, a positive anti-CCP test result occurs almost exclusively in people with RA. A positive result might even identify people who are at risk for getting the disease, such as those with a family history of it.

Because neither test is 100% indicative of RA, they’re used as part of the diagnostic process rather than as sole indicators.

Where both serostatus tests fall short is in their sensitivity, which is generally below 80%. What this means is that, while valuable in the diagnostic process, the tests are prone to ambiguity or falsely negative results.

Inflammatory Markers

Inflammation is a defining characteristic of rheumatoid arthritis, and certain markers in your blood reveal information about inflammation to your healthcare provider. Tests that look at key markers not only help confirm the initial diagnosis of RA but are used periodically to see how well you’re responding to treatment.

Two common tests of inflammatory markers are:

  • Erythrocyte sedimentation rate (ESR or sed rate) is a test that measures how long it takes red blood cells to settle to the bottom of a long, upright tube, known as a Westergren tube. When there’s inflammation, the red blood cells stick together and sink faster. It is a non-specific measurement of inflammation but can provide key insights that are valuable to a diagnosis.
  • C-reactive protein (CRP) is a type of protein the liver produces in response to inflammation. While also non-specific, it is a more direct measure of your inflammatory response.

ESR and CRP can also be used to diagnose arthritis remission, a state of low disease activity in which inflammation is more or less in check.

Your healthcare provider may order other tests to gauge your disease progression, as well.

Imaging Tests

The role of imaging tests in rheumatoid arthritis is to identify the signs of joint damage, including bone and cartilage erosion and the narrowing of the joint spaces. They can also help track the progression of the disease and establish when surgery is needed.

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Each test can provide different and specific insights:

  • X-rays: Especially useful in identifying bone erosion and joint damage, X-rays are considered the primary imaging tool for arthritis. However, they’re not as helpful in the very early stages of the disease, before changes in cartilage and synovial tissues are significant.
  • Magnetic resonance imaging (MRI): MRI scans are able to look beyond the bone, spot changes in soft tissues, and even positively identify joint inflammation in the early stages of the disease.
  • Ultrasounds: These scans are also better than X-rays at spotting early joint erosion, and they can reveal specific areas of joint inflammation. This is a valuable feature, given that inflammation can sometimes linger even when the ESR and CRP point to remission. In such cases, treatment is continued until you’re truly in remission.

Classification Criteria

In 2010, the American College of Rheumatology (ACR) updated its longstanding classification criteria for rheumatoid arthritis. The revisions were motivated, in part, by advances in diagnostic technologies. While the classifications are intended to be used for clinical research purposes, they help healthcare providers be more certain about your diagnosis.

While healthcare providers are the only ones who use these criteria, looking at them can help you understand why an RA diagnosis often can’t be made quickly or easily.

The 2010 ACR/EULAR Classification Criteria looks at four different clinical measures and rates each one on a scale of 0 to 5. A cumulative score of 6 to 10 can provide a high degree of confidence that you do, in fact, have rheumatoid arthritis.

Progression

The strongest indicator of progressive joint damage in rheumatoid arthritis is considered to be seropositivity. That said, seronegativity doesn’t preclude progressive joint damage.

Factors that point to a poor prognosis with progressive joint damage include:

People who test positive for both rheumatoid factor and anti-CCP are more likely to have a rapid progression of joint damage than people who are positive for one or the other.

  • X-ray evidence or clinical evidence of joint damage
  • Increased number of joints involved with active synovitis, tenderness, swelling, or joint effusions
  • Elevated ESR or CRP
  • Positive for anti-CCP
  • High level of medication use, including corticosteroids, used to treat inflammation in the affected joints
  • An inadequate response to medications
  • Decreased joint function as determined by the Health Assessment Questionnaire
  • Declining quality of life

Remission

Diagnosing disease remission is not as straightforward as diagnosing the disease in the first place. It requires not only diagnostic tests but a subjective assessment of what you feel about your condition. Accurately diagnosing remission is important because it determines whether certain treatments can be stopped or if going off of them is likely to cause a relapse.

To this end, the ACR has established what is called the DAS28. DAS is an acronym for disease activity score, while 28 refers to the number of joints that are examined in the assessment.

The DAS involves four scores:

  • The number of tender joints your healthcare provider finds (out of 28)The number of swollen joints your healthcare provider finds (out of 28)Your ESR and CRP results (normal versus abnormal)Your rating of how you feel and your overall health, ranging from “very good” to “very bad”

These results are put through a complex mathematical formula to calculate your overall score.

Other Diagnoses

Just as certain tests can help differentiate between rheumatoid arthritis and osteoarthritis, other tests may be ordered to find out whether your symptoms could be caused by another condition. This is especially likely if your RA test results are either inconclusive or negative.

Conditions with similar symptoms include other autoimmune disorders as well as connective tissue, neurological, and chronic inflammatory diseases such as:

  • Fibromyalgia
  • Lyme disease
  • Myelodysplastic syndromes
  • Paraneoplastic syndromes
  • Polymyalgia rheumatica
  • Psoriatic arthritis
  • Sarcoidosis
  • Sjögren’s syndrome
  • Systemic lupus erythematosus (lupus)

Frequently Asked Questions

  • What blood tests are used to diagnose rheumatoid arthritis?
  • Blood tests used to diagnose RA measure either serostatus or inflammation. Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) are used to establish serostatus. Erythrocyte sedimentation rate (ESR or sed rate) and C-reactive protein (CRP) are used to measure inflammation.
  • What is considered positive for rheumatoid factor?
  • The normal range for the RF test is 20 IU/ml or less. Test results above 20 IU/ml are considered positive for rheumatoid factor. However, about 20% of people with RA test negative for RF and about 5% of people who test positive for RF do not have RA.
  • What does a positive anti-CCP test mean?
  • A positive anti-CCP test typically indicates rheumatoid arthritis. An anti-CCP test is considered positive if it is above 20 units. A negative anti-CCP test does not rule out RA, however, as about 20% of RA patients are seronegative for anti-CCP.

Blood tests used to diagnose RA measure either serostatus or inflammation. Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) are used to establish serostatus. Erythrocyte sedimentation rate (ESR or sed rate) and C-reactive protein (CRP) are used to measure inflammation. 

The normal range for the RF test is 20 IU/ml or less. Test results above 20 IU/ml are considered positive for rheumatoid factor. However, about 20% of people with RA test negative for RF and about 5% of people who test positive for RF do not have RA. 

A positive anti-CCP test typically indicates rheumatoid arthritis. An anti-CCP test is considered positive if it is above 20 units. A negative anti-CCP test does not rule out RA, however, as about 20% of RA patients are seronegative for anti-CCP.

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By Carol Eustice

Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.

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