Diagnosing Rheumatoid Arthritis Can be Challenging-Here is What You Need to Know

Rheumatoid antibodies Imaging & disease activity are used and monitored to confirm diagnosis and ensure Rx is working

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor updated 7/2019

​There is no single test that confirms the diagnosis, and symptoms can vary from person to person and be similar to those of other joint conditions. Establishing the diagnosis early in the course of disease is important, however, because early diagnosis and treatment of RA helps to minimize joint damage.

If you or your doctor suspect that you have RA, you may wish to see a rheumatologist—a physician who specializes in the diagnosis and treatment of arthritis and other diseases of the joints, muscles and bones.

Tests for Rheumatoid Arthritis

If you are experiencing symptoms of RA, such as pain, swelling, and stiffness of joints, your doctor may use several different approaches to establish the diagnosis.1

Medical history: It will be helpful for your doctor to know what symptoms you have, how severe the symptoms are, when the symptoms began, and how the symptoms have changed over time. It’s also important for your doctor to know about any medications that you use and any other health conditions that you have. If you have information about your family’s medical history, that can be helpful as well.

Physical Examination: In addition to performing a general physical examination, your doctor will examine the affected joints.

Laboratory tests: Blood tests can identify changes that are characteristic of rheumatoid arthritis. Your doctor may assess some or all of the following:

  • Rheumatoid factor (RF): Many people with RA will test positive for an antibody called rheumatoid factor. RF is not a perfect marker of RA, however, because some people with RA test will test negative, and some people without RA will test positive.
  • Anti-citrullinated protein antibody (ACPA): This is another antibody that is often present in people with RA. ACPA may be detectable very early in the course of the disease (in some cases, even before symptoms develop).
  • Tests for inflammation: RA involves inflammation, and two commonly used tests for inflammation are the erythrocyte sedimentation rate (the “sed rate”) and a test for C-reactive protein (CRP).
  • Other tests: Other tests may also be performed, including a test for anemia. Anemia is common in people with RA.

Imaging: Tools such as X-rays, magnetic resonance imaging (MRI) or ultrasound may be used to assess the presence and extent of damage within joints. Early in the course of RA, however, there may be no apparent damage.

Making the Diagnosis

Based on all of the available information, you doctor will decide how likely it is that you have RA and what the optimal approach to treatment and follow-up is.

In 2010, the American College of Rheumatology and the European League Against Rheumatism developed new classification criteria for RA. These criteria are intended to improve the identification of people with early RA. The criteria consider many of the factors described above, including the extent of joint involvement, blood test results, and duration of symptoms.2

In some cases, the initial diagnosis may be uncertain. Additional visits and testing over time may allow for a more definite diagnosis.

Measuring Disease Activity

The more you and your doctor know about your RA, the better you can manage it. Your doctor will regularly monitor your disease activity, which is the term used to refer to ongoing inflammation, symptoms, and/or joint damage. This regular and systematic monitoring is critical to managing the condition.[1] Information about the level of disease activity allows doctors to monitor your response to treatment and to adjust your treatment as needed.

One commonly used measure of disease activity is the DAS28 (Disease Activity Score with 28 joint counts). The DAS28 involves a count of tender and swollen joints, your own assessment of your health, and lab tests to identify inflammation. The lab tests measure the erythrocyte sedimentation rate (ESR) or levels of C-reactive protein (CRP). Other composite measures of RA disease activity are also available.

A newer way to measure disease activity is with the Vectra DA test, which is an innovative blood test that allows doctors to test for several biological markers (or biomarkers) of RA simultaneously. The test must be ordered by a physician. Vectra DA measures the levels of 12 proteins in the blood—biomarkers that have been linked to RA disease activity—and then combines them into a single score (between 1 and 100) that classifies your current level of RA disease activity as “low”, “moderate”, or “high”. The test does not replace a doctor’s evaluation, but it does provide a precise, objective measure of the underlying biology of your RA. Testing with Vectra DA can provide snapshots of your disease activity at specific points in time, which can help you and your doctor to better manage your RA.

Understanding Biomarkers for Diagnosis & Prognosis of Rheumatoid Arthritis

The main biomarkers for RA are autoantibodies, which are indicative of an immune system imbalance. Which autoantibodies test positive can help a doctor diagnose RA and generate a prognosis. Here are the commonly-used biomarkers and what they can mean for RA prognosis and treatment.(3,4)

What are autoantibodies?

Antibodies are produced by immune cells and normally recognize and bind to foreign substances. Some antibodies however are made that will specifically recognize modified self-proteins. These are known as autoantibodies. Autoantibodies are responsible for the inflammation in RA and some can be measured and are used to diagnose the disease. Which types are present, and their relative abundance, can also serve as prognostic factors.(3,4)

Rheumatoid factor (RF)

Rheumatoid factor (RF) is an autoantibody that attacks healthy tissue in the body. RA, it is found in 53-80% of RA patients and can be detected in the blood up to ten years prior to the onset of symptoms in RA patients. Not everybody who tests positive for RF however will develop RA.(4,5) Individuals with RA who have RF have a greater chance of developing joint erosion damage, and an even higher risk if present in conjunction with other RA biomarkers.(5,6)

Anti-citrullinated protein antibodies (ACPA)

During inflammation, some amino acids in proteins get converted into citrulline molecules and immune cells will produce antibodies that recognize and bind to proteins that have been citrullinated. These are called (ACPA). ACPA are present in about 50-78% of individuals with RA and can also be detected as early as ten years before symptoms develop. Like RF however, not all people who test positive for ACPA end up with RA later in their lives.(6,7,8) ACPA positivity is associated with higher inflammation, as well as higher disease activity, and very high levels have been shown to correlate with more severe disease.

Anti-CarP antibodies

Distinct from citrullinated proteins, some proteins undergo carbamylation and the body can develop antibodies which recognize and bind to carbamylated proteins. These are called anti-CarP antibodies, and are also useful biomarkers for the diagnosis and prognosis of RA. Anti-CarP is not as specific for RA as ACPA and occur less frequently; only 34-53% of RA patients have anti-CarP antibodies. in their blood. Anti-CarP are a useful marker for determining the status of RA in patients where the traditional biomarkers otherwise could not.(9-11) The presence of anti-CarP antibodies is associated with a more active disease. When anti-CarP antibodies are present along with ACPA, the chance of joint erosion increases even more. (12,13)

Next: Treatment & Management of RA

​References

  1. National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Disease. Handout on Health: Rheumatoid Arthritis.
  2. Aletaha D, Neogi T, Silman AJ et al. 2010 Rheumatoid Arthritis Classification Criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis & Rheumatism. 2010;62:2569-2581.
  3. Malmstrom V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nature reviews Immunology. 2017;17(1):60-75.
  4. Bugatti S, Manzo A, Montecucco C, Caporali R. The Clinical Value of Autoantibodies in Rheumatoid Arthritis. Frontiers in medicine. 2018;5:339.
  5. Tiwari V, Bergman MJ. Rheumatoid Factor. In: StatPearls. Treasure Island (FL): StatPearls Publishing LLC.; 2018
  6. Harrison MJ, Paget SA, Niewold TB. Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis. QJM: An International Journal of Medicine. 2007;100(4):193-201. 7. Alivernini S, Galeazzi M, Peleg H, et al. Is ACPA positivity the main driver for rheumatoid arthritis treatment? Pros and cons. Autoimmunity reviews. 2017;16(11):1096-1102.
  7. Sakkas LI, Daoussis D, Liossis SN, Bogdanos DP. The Infectious Basis of ACPA-Positive Rheumatoid Arthritis. Frontiers in microbiology. 2017;8:1853.
  8. Verheul MK, Böhringer S, van Delft MAM, et al. Triple Positivity for Anti–Citrullinated Protein Autoantibodies, Rheumatoid Factor, and Anti–Carbamylated Protein Antibodies Conferring High Specificity for Rheumatoid Arthritis. Arthritis & Rheumatology. 2018;70(11):1721-1731.
  9. Li L, Deng C, Chen S, et al. Meta-Analysis: Diagnostic Accuracy of Anti-Carbamylated Protein Antibody for Rheumatoid Arthritis. PloS one. 2016;11(7):e0159000.
  10. Regueiro C, Nuño L, Ortiz AM, et al. Value of Measuring Anti-Carbamylated Protein Antibodies for Classification on Early Arthritis Patients. Scientific Reports. 2017;7(1):12023.
  11. Shi J, Knevel R, Suwannalai P, et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(42):17372-17377.
  12. Truchetet ME, Dublanc S, Barnetche T, et al. Association of the Presence of Anti-Carbamylated Protein Antibodies in Early Arthritis With a Poorer Clinical and Radiologic Outcome: Data From the French ESPOIR Cohort. Arthritis & rheumatology (Hoboken, NJ). 2017;69(12):2292-2302.
  13. Humphreys JH, Verheul MK, Barton A, et al. Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis: results from the Norfolk Arthritis Register. Annals of the Rheumatic Diseases. 2016;75(6):1139.
    Markusse IM, de Vries-Bouwstra JK, Han KH, et al. Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis. Arthritis research & therapy. 2014;16(5):430.
Comments (1)
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Rising Above ra
Rising Above ra

Editor

I’ve done all these tests except I don’t recall getting the ACPA test done, although I wish the general physician helped catch it earlier (diagnosed after two years with random symptoms appearing and my doctor didn’t think anything was wrong). I felt the Vectra DA test has been such a blessing to this medical community. Some doctors use this as a guide to decide which medicine would work for their patient best, while other doctors don’t care much for it. It has helped gauge my disease progression relatively accurately though and showed which markers were the highest in driving the cartilage damage.