Blood Tests for Rheumatoid Arthritis, part 2

Substantial numbers of RA’ers have “normal” test results

In my last post, I posed the question: Is There a Blood Test for Rheumatoid Arthritis? I told you that the answer is yes – and no. I went on to describe the “yes” by summarizing four principal blood tests used in diagnosing Rheumatoid Arthritis. Now it is time to elaborate upon the “no.”

I found this startling:

You may already know that there is not a blood test to definitively measure Rheumatoid Arthritis. No blood test can be used to precisely diagnose RA in all patients. But just as importantly, there is not a test which can reliably gauge the degree of RA within a patient.

But, wait, it gets more interesting:

The most thorough study of the usefulness of these tests was a large study conducted in both Finland and Tennessee. Almost 2,500 patients were studied over a period of 25 years. The CRP, sed rate (ESR), and Rheumatoid factor (Rf) were all monitored.

Look at some of the results. ESR was normal in 45% (Finland) and 47% (Tennessee) of patients. CRP was normal in 44% and 58%. And all Rheumatoid factor (Rf) tests were negative in 38% and 37% of patients.

Why does this matter?

Doctors commonly use these three tests to “monitor disease activity.” That means they are looking to these numbers to show whether the disease is active and whether a patient’s current treatment plan is adequate. Some doctors are more reliant upon them than others. I have met one rheumatologist who says that he relies upon them completely.

So read this carefully:

Many RA’ers experience plenty of active and damaging Rheumatoid Arthritis while one or all of these indicators are “normal.”

Here are a few cases in point:

~ “Sometimes also patients with rheumatoid arthritis have low CRP response in relation to the severity of the disease.” Axis-shield

~ “By the same token a normal sed rate is meaningless in a patient with known SLE if they are having symptoms of a flare." (Sounds like this rheumatologist considers the lab test pretty useless to measure flares in Lupus.) Nathan Wei, MD, FACP, FACR

~ “However, a low CRP level does not always mean that there is no inflammation present. Levels of CRP may not be increased in persons with rheumatoid arthritis and lupus. The reason for this is not known.” University of Southern California

~ “Many people with active RA have inactive values of ESR/CRP and many with inactive RA have active values.” Journal of Rheum.

~ “Both ESR and CRP were normal in 33% and 42% of patients” in the large study mentioned earlier. Journal of Rheum. abstract

What is the bottom line?

Only a small percentage of RA’ers actually had abnormal results to all three blood tests (ESR, CRP, and Rf) in the huge Finland / Tennessee study. “All 3 tests were abnormal in only 28% in Jyväskylä (Finland) and 23% in Nashville (Tennessee).” The authors of the study concluded: “Normal ESR, CRP, and RF are seen in a substantial proportion of patients with RA at this time.” Journal of Rheum. abstract

There is hope.

I had already spent many grueling hours researching for this series when I happened upon an article entitled The Many Myths of Erythrocyte Sedimentation Rate and C-Reactive Protein. I was thrilled to find a rheumatologist who holds the following viewpoint. “Learning when to ignore a test and when to rely on it lies at the heart of good medical care… It is, perhaps, time for more research about testing and measurement in clinical practice.” I recommend the article in the Journal of Rheumatology by Frederick Wolfe, M.D.

Is there a blood test for Rheumatoid Arthritis? Part 1

Yes and no. There are at least four. But, actually, there is none. Allow me to explain…

Do the tests pass the tests?

What are the tests?

1) Rheumatoid Factor

For the last few decades, Rheumatologists have relied heavily enough upon the Rheumatoid factor test that it is part of the American College of Rheumatology (ACR) guidelines for diagnosis. However, many Rheumatoid Arthritis patients do not have high enough levels of this antibody to be considered “Rf positive.”

Those RA’ers are referred to as “seronegative.” Sometimes, I think they are considered the stepchildren of the RA community. Too often, they are initially told by their doctors that they do not even have Rheumatoid Arthritis. Of course, that makes it impossible for them to receive that “early aggressive treatment” which the ACR is now urgently recommending.

The Rheumatoid factor is actually only one of the antibodies which can be found in people with Rheumatoid Arthritis. I think it got to be the one called “Rheumatoid factor / Rf” because it was the first one identified. It is an antibody to immunoglobulin. It was discovered in 1940 using sheep blood cells.

Another problem with the Rf test is the number of false positives. At least 2% of the general population test Rf positive.

2) Anti- Cyclic Citrullinated Peptide

The anti-cyclic citrullinated peptide is another antibody (immune protein). It is directed against certain amino acids (peptides) containing citrulline. It is often called the anti-CCP.

The anti-CCP has excellent prognostic value because it is strongly associated with more aggressive forms of Rheumatoid Arthritis. This is also a more specific test, which means that, if it is present in the blood, there is a 90-95% probability that there is RA. And CCP antibodies are often present in blood years before symptoms develop. It could be used to pursue early diagnosis for the all-important “early treatment.”

3) Sed Rate

The erythrocyte sedimentation rate is also called the sed rate or the ESR. The sed rate is a simple screening test. Blood is allowed to settle in a test tube for one hour. The reading or “rate” is the number of millimeters of red blood cells that fall to the bottom of the tube in one hour.

The sed rate is considered an inflammatory indicator. High rates often correlate with inflammation. An extremely high sed rate is often the first indicator of a cancer tumor, for example. However, a sed rate itself is not diagnostic, so it usually leads to more tests.

Sed rates can be unreliable unless the blood is handled properly at all times. There are also several conditions other than inflammation which can influence the test results. High sed rates are considered strong indicators, but normal ones are less conclusive.

4) C-Reactive Protein

The C-reactive protein is often referred to as the CRP. This is also a non-specific marker of inflammation. High results indicate acute inflammation. CRP’s are also being used as a measure for heart disease.

However, many physical conditions can either raise or lower the CRP. The patient’s diet or medication regimen can alter a CRP result. There is also a more sensitive version of the CRP test, called the “high sensitivity C reactive protein assay.” (We will have much more on the CRP in the next post!)

Are these tests adequate?

Next time, we will look a bit deeper. Exactly how accurate are these tests? How many RA’ers fail them?

A few footnotes:

Book: Rheumatoid Arthritis by St. Clair, Pisetsky, and Haynes;
University of Maryland Medical Center;
Abstract from ClinicalRheumatology;
American Family Physician