Blood Tests for Rheumatoid Arthritis: What Is Their Role?

test tube flowerProbably the RAW article most often referenced is Blood Tests for Rheumatoid Arthritis, part 2 from over four years ago. People need answers to questions like:

My blood tests show I’m in remission, so why do I still have symptoms?

My doctor said I tested negative for RA, but could I still have it?

What is the role of blood tests in Rheumatoid Arthritis / Rheumatoid Disease?

First, there are TWO main reasons a Rheumatoid Arthritis test is important:

1) To help diagnose RA

2) To help measure RA disease activity

However, if you’ve read much of RAW, you know the test does not yet exist which can reliably do both things for every person with Rheumatoid Disease (PRD). The 2009 posts (part 2 above and Is there a blood test for Rheumatoid Arthritis? Part 1) are a primer for understanding four common tests used for PRD and their limitations. Here’s a summary:

4 common blood tests used in Rheumatoid Arthritis

1) Rheumatoid factor: the first antibody discovered to be commonly present with Rheumatoid Disease (RD), about 70% of the time. Rf is also present in many healthy people who do not develop RD. The percentage of people who show positivity for Rf increases with established disease. There are variations in the antibody that can be tested.

2) Anti-CCP or ACPA: a more recently recognized antibody commonly present with RD, and more specific to RD (so that there are fewer “false positives”). Between 70 and 90 percent of PRD are positive for ACPA.

3) Erythrocyte sedimentation rate or ESR: a test that measures the millimeters of red blood cells that fall in a test tube in one hour. ESR can be increased in pregnancy and in other conditions, including cancer, and often correlates with inflammation. The ESR is often normal in PRD.[1,2]

4) C-reactive protein or CRP: CRP is considered an acute-phase reactant because it can rise dramatically during inflammatory activity. CRP is considered a significant factor in heart disease. Several physical conditions or activities can impact CRP including smoking, diet, and obesity. The CRP is often normal in PRD.[1-4]

With the exception of a cure, a reliable RD test is the proverbial Holy Grail

With a reliable test we could rapidly diagnose RD or even what’s called pre-Rheumatoid Arthritis. We could treat with appropriate aggressiveness, and perhaps predict which treatment would work better on particular patients. In the long run, such tests would help us distinguish various subtypes of RD.[5-7]

A recent article by Ted Pincus[8] further clarifies the roles of two kinds of tests in PRD:

1) Blood tests

2) Patient reported outcome measures (PROM)

Pincus et al. compare Rheumatoid Arthritis treatment to hypertension, diabetes, and high cholesterol, which are also incurable, but are treated to target. However, they emphasize the big difference between RD and these other disease states:

RA differs substantially from hypertension, diabetes, or hyperlipidemia in that there is no single, gold standard biomarker (or any other measure) for diagnosis, management, or prognosis in all individual patients. Biomarkers are of unquestioned importance in RA to understand pathogenesis and develop new therapies: Biological agents would not be available without them. However, biomarkers are limited in clinical application to diagnosis, management, and prognosis of RA… Forty percent of new patients have normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), and > 30% test negative for rheumatoid factor or anti-citrullinated protein antibodies (ACPA).”

The difference is that we don’t have THE BLOOD TEST to emulate the treat to target model in RD. Look for more on biomarkers in the next post in this series.

BUT WE DO HAVE SOMETHING…

Pincus and colleagues have spent decades demonstrating that patient reported outcome measures (such as the HAQ and MDHAQ), in which the patient self reports disease status or physical function, are the most significant markers for “future quality of life and premature mortality in RA (are) not laboratory tests, radiographs, indices, or remission criteria.”

“If remission criteria were met by the majority of patients, support for expensive biological therapies in RA might be likely. However, because most people with RA are not in remission, other documentation of the value of treatment is needed. Patient global estimate and physical function are far more informative than laboratory tests, joint counts, radiographs, indices, or remission criteria to recognize improved RA outcomes. Routine collection of these quantitative data on patient questionnaires in the infrastructure of clinical care to document control to achieve more favorable values, rather than simple notation of gestalt impressions by the physician, would appear to be an intellectual and ethical responsibility to our patients with RA.” (Emphasis added).

PROMs are more reliable than blood tests, but…

A recently published study in Denmark found that patient global estimate (a PROM) was significantly related to outcomes, while CRP had no relationship.[3] But this is not new information: Wolfe concluded four years ago: “Myth 1. Normal values of ESR and CRP are meaningful in RA.”[2] Yet, most of the time, PROMs are not used in treatment for RD, which is a shame. But the biomarkers are clues to better treatments and a cure, so we’ll talk more about those next.

NOTE: Although I’ve told Ted Pincus his work makes him a hero to patients, and his co-author Yusuf Yazici is an RPF advisor, I have one reservation with the quoted article. The introduction states that “remission is now a realistic target in RA,” however this statement needs qualification. A low percentage of patients in the field achieve remission [9,10], so remission is now a realistic target theoretically or perhaps academically, but it should not be made as an unqualified statement.

Recommended reading

The posts that started the discussion: WHAT ARE THESE TESTS WORTH?

FOOTNOTES

1 Sokka T, Pincus T. Erythrocyte sedimentation rate, C-Reactive protein, or rheumatoid factor are normal at presentation in 35%–45% of patients with rheumatoid arthritis seen between 1980 and 2004: Analyses from Finland and the United States. 2009 May  [cited 2013 Oct 16];36(7):1387-1390.  Available from: http://jrheum.org/content/36/7/1387.abstract

2 Wolfe F. The many myths of erythrocyte sedimentation rate and C-reactive protein. J Rheumatol [Internet]. 2009 Aug [cited 2013 Oct 16];36(8):1568-1569. Available from: http://jrheum.org/content/36/8/1568.full

3 Linde L, Sørensen J, Østergaard M, Hetland ML. Gain in quality-adjusted life-years in patients with rheumatoid arthritis during 1 year of biological therapy: A prospective study in clinical practice. J Rheumatol [Internet]. 2013 Jul 1 [cited Oct 16];40(9):1479-1486. Available from: http://www.jrheum.org/content/40/9/1479.full

4 Teitel AD. C-reactive protein. Medline Plus – National Institutes of Health [Internet]. 2013 Mar 22 [cited 2013 Oct 16]. Available from: http://www.nlm.nih.gov/medlineplus/ency/article/003356.htm

5 Chen DY, Chen YM, Chen HH, Hsieh CW, Lin CC, Lan JL. Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-a therapy. Arthritis Res Ther [Internet]. 2011 [cited 2031 Oct 16];13(4):126. Available from: http://arthritis-research.com/content/13/4/R126

6 West R. Fundamental studies of rheumatoid arthritis genetics & genomics. Rheumatoid Arthritis Warrior [Internet]. 2011 Jul 11 [cited 2013 Oct 16]. Available from: http://www.rawarrior.com/fundamental-studies-of-rheumatoid-arthritis-genetics-genomics/

7 Young K. Evidenced-based medicine or easy-bake oven: Tension between evidence and reality. Rheumatoid Arthritis Warrior [Internet]. 2011 Aug 5 [cited 2013 Oct 16]. Available from: http://www.rawarrior.com/evidenced-based-medicine-or-easy-bake-oven-tension-between-evidence-reality/

8 Pincus T, Castrejón I, Yazici Y. Documenting the Value of Care for Rheumatoid Arthritis, Analogous to Hypertension, Diabetes, and Hyperlipidemia: Is Control of Individual Patient Self-Report Measures of Global Estimate and Physical Function More Valuable Than Laboratory Tests, Radiographs, Indices, or Remission Criteria? J Rheumatol [Internet]. 2013 Sep [cited 2013 Oct 16];40(9):1469-1474. Available from: http://www.jrheum.org/content/40/9/1469.full?

9 Prince FHM, Bykerk VP, Shadick NA, Lu B, Cui J, Frits M, Iannaccone CK, Weinblatt ME, Solomon DH. Sustained rheumatoid arthritis remission is uncommon in clinical practice. Arthritis Res Ther [Internet]. 2012 Mar 19 [cited 2013 Oct 16];14(2):R68. Available from: http://arthritis-research.com/content/pdf/ar3785.pdf

10 Young K. Sustained rheumatoid arthritis remission is rare. Rheumatoid Arthritis Warrior [Internet]. 2012 Mar 30 [cited Oct 16]. Available from: http://www.rawarrior.com/sustained-rheumatoid-arthritis-remission-is-rare/

Kelly Young

Kelly Young is an advocate providing ways for patients to be better informed and have a greater voice in their healthcare. She is the president of the Rheumatoid Patient Foundation. Kelly received national acknowledgement with the 2011 WebMD Health Hero award. Through her writing, speaking, and use of social media, she is building a more accurate awareness of Rheumatoid disease aka Rheumatoid Arthritis (RA) geared toward the public and medical community; creating ways to empower patients to advocate for improved diagnosis and treatment; and bringing recognition and visibility to the Rheumatoid patient journey. In 2009, Kelly created Rheumatoid Arthritis Warrior, a comprehensive website about RA of about 950 pages and writes periodically for other newsletters and websites. Kelly served on the Mayo Clinic Center for Social Media Advisory Board. There are over 42,000 connections of her highly interactive Facebook Fan page. She created the hashtag: #rheum. Kelly is the mother of five, a home-schooler, Bible teacher, NASA enthusiast, and NFL fan. You can also connect with Kelly by on Twitter or YouTube, or LinkedIn. She has lived over nine years with unrelenting Rheumatoid disease. See also http://www.rawarrior.com/kelly-young-press/

17 thoughts on “Blood Tests for Rheumatoid Arthritis: What Is Their Role?

  • October 17, 2013 at 11:05 am
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    I was diagnosed with Rheumatoid Arthritis three years ago. I have been on plaquenil for two and a half years. In the past year bloodwork from my Internist and Rheumy have shown a low white blood cell count of 3.5 Is this something I should be concerned about? Is this normal for most patients on plaquenil?

    Reply
  • October 17, 2013 at 12:26 pm
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    I find the blood test conundrum to be fascinating. The tests used for RD are notoriously unreliable, and the ACR’s own website says so. Yet, how many of us have been misdiagnosed or left untreated because of negative or “not positive enough” results on blood tests?

    I guess much of it stems from the fact that doctors are heavily trained in science and want to see undeniable black and white proof before diagnosing something. The drugs we take are not to be taken lightly, which probably adds to the reluctance to diagnose without positive proof. X-rays aren’t too reliable either, especially in the earlier stages before damage has occured. Ultrasound seems to be much more accurate but isn’t widely used. That leaves the patient’s description of what is happening. The good doctors listen carefully to that. Too bad there aren’t enough GOOD ones to go around!

    I have been recently diagnosed with PsA. One of the criteria used to diagnose it is NEGATIVE results on the standard blood tests! Even with a personal history of psoriasis,nail involvement, sausage digits, etc., it took a third rheumatologist to correctly diagnose the obvious.

    It’s too bad that there aren’t better blood tests. Maybe someday.

    Reply
  • October 17, 2013 at 1:34 pm
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    Kelly, thank you for this update on blood tests. Your work continues to change the practice of rheumatology and RD patient care. I am forever grateful to you and your colleagues.

    I agree with your information about blood tests and the importance of patient reporting. Unfortunately if patient voices are paired with inconclusive blood tests, what can happen yet again is the proverbial fight between the rheumatologist and patient. I don’t think your blog post provided a way around this. Frankly, I’m tired of seeing the same information from patients about negative blood tests and then not being believed by their rheumatologists no matter what the patient reports. Enough already.

    One suggestion is this: a “standard of care” for diagnosis of RA needs to be updated by the American College of Rheumatology and the European League Against Rheumatism. There was some recognition in the 2010 ACR guidelines of the importance of advanced imaging in rheumatology care. Since 2010, many peer-reviewed journal articles have been published that lend further evidence to the importance of advanced imaging in rheumatology care. Here are two examples:

    The EULAR (2013) guidelines on advanced imaging http://ard.bmj.com/content/early/2013/03/20/annrheumdis-2012-203158.full.pdf+html

    Cates (2013) systematic review of the literature on ultrasonography in rheumatology , http://arthritis-research.com/content/15/1/R4

    THE USE OF ULTRASOUND AND MRI NEEDS TO BE INCLUDED IN THE STANDARD OF CARE IN RHEUMATOLOGY because there is no definitive blood test for diagnosis of RA and clinical exam of joints is not as valid as advanced imaging. You cannot argue with an objective imaging scan that shows 1) erosions of the surface of bone in the joints, 2) active inflammation in joints, and 3) excess blood flow to the joints (hyperemia). Having objective evidence takes the focus off of patient reporting and might lessen arguments with rheumatologists.

    So, my vote would be that the ACR guidelines for the “standard of care” for diagnosis and monitoring of disease activity in rheumatoid arthritis include the following four components:
    • clinical exam of joints by the rheumatologist
    • blood work (RF, anti-CCP, ESR, CRP)
    • advanced imaging (MRI or power Doppler ultrasound). X-rays are obsolete
    • patient reports using standardized questionnaires like RAPID3

    Given how fast medicine changes, it is time for an update to the 2010 Rheumatoid Arthritis Classification Criteria An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative ACR and EULAR.

    Reply
  • October 17, 2013 at 2:24 pm
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    I had the CCp test positive and now a yr leater its negitive. is this normal?

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  • October 17, 2013 at 8:46 pm
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    Hi Kelly. What does the “P” stand for in PRD?

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  • October 18, 2013 at 5:39 am
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    Ah, the blood tests. I visit the vampires pretty darn often, but it’s mostly used to check the health of organs in my body and their reactions to my cornucopia of drugs. We are checking sed as an indicator of this particular round of current meds (rituxan) but mostly my Rheumy relies on me. We talk about swelling and she does count joints, but the notes she takes are more from her first view of me and our discussions. Trust me, it’s obvious when a medication is in failure.

    I severely dislike the talk about remission as it’s such a small chance. When I was diagnosed it was held out to me as a goal, and an attainable one. Recently I looked my Rheumy in the eye and said, yanno, at this point unless some miracle comes along I’m pretty sure we can take remission off the table.

    The dream of remission held me back from accepting my diagnosis and my new life. Who I am now, versus who I was three years ago, are two different people. I think the acceptance and the comfort from wrapping my head around that, would have been easier without the hope of remission.

    I am grateful now for the life I lead, and I am able to be more present in my life knowing that is not an option. It may sound fatalistic, but it’s not.

    Be blessed,

    Jennifer

    Reply
  • October 18, 2013 at 6:41 am
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    I have a negative RA factor and anti-CCP. My sed rate and CRP have always been normal. I am so thankful that my rheumatologist has treated me aggressively based on symptom reports and synovitis alone. I have been through Planquenil only therapy, progessed to triple therapy, then tried Enbrel, Humira, & Orencia. I’m finally feeling the best I have in a few years with Actemra infusions combined with merhotrexate injections and Plaquenil. This therapy has allowed me to continue my full-time job and taking care of my family. I know I am very lucky.

    Reply
  • October 18, 2013 at 9:00 am
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    In regards to the Vectra DA testing you just updated everyone on, I spoke to my Rhuemy and at this time he does not recommend it. Insurance will not pay and the test is a substantial cost. He is also hesitant due the fact there are not enough case history’s. Reading the website it sounds like a wonderful test. Hopefully, it is not all sales pitch.

    Reply
    • October 18, 2013 at 9:21 am
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      Lynn, we’ve discussed Vectra DA several times on the blog & I know we’ve covered this part, so let your doc know that the company who sells the test has a generous patient program that makes the cost of the test lower if your insurance doesn’t cover. I’m pretty sure the most anyone could ever pay is about 100$ if you have pretty high income. Also the test is now covered by Medicare, so many insurance does cover it since they follow the government’s lead.
      I don’t think it’s the one test to end all – which everyone keeps hoping for. But we have had a few people finally get adequate treatment when the Vectra DA test worked for them.

      Reply
  • October 18, 2013 at 9:45 am
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    I was diagnosed in July based on symptom report and my RF and anti-CCP were sky high. I was told I had textbook RA (whatever that means). I have been on MTX since then and have no more pain or swelling/stiffness. Thankful to be back to my old self 🙂 BUT, my blood work is WORSE now than before I was diagnosed. My doctor says this is normal, but how it that possible? If the labs are so bad, are my joints being damaged even with zero pain or swelling? HELP!

    Reply
  • October 18, 2013 at 2:28 pm
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    Kelly, thank you for the reply. My point to the Dr was exactly that. If we can identity more accurately, it would be to everyone’s best interest who has to deal with this disease. I obviously missed the prior postings. Thanks for all u do. As more patients push for the testing, this will help get this test more available and physicians on board with it.

    Reply
  • November 4, 2013 at 9:50 am
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    I am an RN so when I went in for symptoms of bilateral knee, hip, shoulder, elbow and jaw pain after a scare from the dentist due to him thinking I was much older than 25 from bone erosion and remodeling on my xrays I thought my sed rate would definitely show inflammation. I was stiff, sore and fatigued beyond belief. My sed rate came back at 5, my RA factor came back at 26, my lymes titer was negative, ANA negative, everything was WNL on my CBC and I am awaiting results still on my CCP. Even though I don’t have an official RA diagnosis yet…I know that is what I have. My paternal grandmother committed suicide from the pain of Raynauds and RA, my paternal aunt is seronegative, her son was diagnosed at the age of 9 with psoriatic RA, and my maternal aunt has DM and UCTD. I firmly believe genetics plays a strong role in autoimmune diseases. I haven’t been referred to a rheumatologist yet; however, since my appointment with a GP last week I now have a numbness/tingling/burning sensation from my elbows into my hands as well as intermittent stiffness in my left hand and foot. It is scary to know that I no longer have control over my body. My joints snd hands constantly feel like there is icy hot on them. I am nervous for what the future holds. I just got married in August and wonder about how/if I will ever be able to have children. For now, I am keeping my faith in God to make me stronger and praying for the best posdible outcome.

    Reply
  • Pingback: #491 – Fear and Blood Tests | A Rheumful of Tips

  • January 27, 2014 at 6:48 am
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    My current RF score is 1800 up 80% since August. I am on Actemra, Methotrxate and Prednisolone. Both my GP and rheumatologist believe I am much better. I am better from the terrible pain state I was in 12 months ago but why such a high RF measure? Neither my own research or the two clinicians in question can explain. It seems to me that 1) i could be living on borrowed time; 2) measuring RD is still an art and not a science or 3) there is something missing in the jigsaw. I had a total knee replacement last June and I wonder if the titanium joint has contributed. Perhaps others have had similar experiences?

    Reply
  • October 24, 2014 at 8:30 pm
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    I enjoyed reading this article because for the last three months I’ve been off Methotrexate after taking it was over 6 years. I discontinued it because it caused me to have Tinnitus, ringing in the ear due to nerve damage from medication, per my ENT. Plus, other side effects that I could no longer tolerate. Even though I my Sed Rate is high I haven’t experienced high levels of pain or much pain at all. I was so surprised! I do have some Prednisone for just in case. My rheumatologist told me for the first time ever that the physical exam determines the severity of the disease and based on the exam I have a mild case of RAD. II will begin taking Plalenqil, after seeing an Ophthalmologist. I was diagnosed with RAD in 2007 and I still don’t understand all there is to know about it, but thanks to RAW I’m slowly learning.

    Reply

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