Many times as rheumatologists, we are asked about lab testing in patients with rheumatic problems. This article will mix some of the political, operational and mechanical issues within this topic. Most important above the entire lab testing is the history and physical examination.
The labs tests are a guide that helps define our patients, but the history and physical are the main guides to proper management.
The Centers for Medicare & Medicaid Services (CMS) took away the consultation code for specialists in January 2010. Nevertheless, it is careful examination and clinical evaluation that saves more in costs.
Now, on to a discussion of the lab tests available and how they may help confirm a diagnosis. There are five main tests used in the rheumatology field to help make a diagnosis:
1. Westergren Sedimentation Test: This simple test for inflammation, if done correctly and fresh and NOT sent to a central lab like QUEST, Solstas, or LabCorp, can give us a lot of information about the status of the patients and their rheumatic complaints. It is not specific for a diagnosis; in fact, it was originally developed in the 1930s as a pregnancy test because it would rise during pregnancy and then fall after delivery. Even then, in the 1930s, they knew that any delay in performing the test would lessen numerical final result.
In my office, we run fresh sed rates despite the fact that some of the insurance companies would not pay for the correct test. I am surprised the central labs have not made that clearer on their lab reports.
2. C Reactive Protein (CRP): This, too, is a simple test for inflammation. It is reported either as mg/dL or for high sensitivity mg/L. Therefore, it is about a 1:10 difference. We look at this test to judge inflammation. Of interest in Rheumatoid Arthritis (RA), there is about a 30+ percent discordance in that some people will have the sedimentation rate elevated or the CRP elevated, and about two-thirds will have both elevated. They measure different things. The high sensitivity is used by some to look at cardiovascular risks. In our Rheumatoid Arthritis (RA) patients, it is already high, consistent with the increased cardiovascular disease associated with inflammatory disease. Patients with RA have a higher cardiovascular risk, and people with RA die up to 10 years earlier with cardiovascular disease compared to the general population.
Of note: some of our medications including methotrexate and the biological Tumor Necrosis Factor inhibitors are making a dent in this risk and improving cardiovascular risk in RA.
3. Rheumatoid Factor (RF): This is found in about 80 percent of people with Rheumatoid Arthritis (RA). It is not specific for RA and is the body’s response to a chronic inflammatory condition. The most common cause of elevation of the RF in the world is malaria. We use it in rheumatology to help validate the diagnosis of RA using criteria for classification of RA by the American College of Rheumatology Criteria. It can be elevated in chronic infections such as endocarditis, and as the endocarditis is cured with antibiotics the elevated RF can normalize.
4. Cyclic Citrullinated Protein (CCP): This test is used now to help us diagnose Rheumatoid Arthritis, and also to judge the severity of RA. Those with the genetic risk of RA have potentially a higher risk of developing RA if they have smoked and carry either a single or double HLA-DR shared epitope(SE) gene and are anti-CCP positive. If you have smoked, you are at greater risk of having more severe RA, and it may not respond as well to therapy. Unfortunately, stopping smoking does not seem to help. The presence of both a positive RF and a positive CCP indicates a risk for more severe RA no matter else. Rheumatologists often order both the RF and CCP in combination for diagnosis and prognosis.
5. Antinuclear Antibody (ANA): This is a test indicating the presence in the body of an antibody against the nucleus of the cell. Everyone has a positive ANA, but people with lupus and other members of the connective tissue disease family have a higher positive ANA. This test, when positive, is one of the criteria for the diagnosis of Systemic Lupus Erythematosus. Its presence is not specific for lupus. In fact, a positive ANA can be seen in people who have no demonstrable disease. A positive ANA can also be seen in allergic reactions, other connective tissue disease and certain types of autoimmune hepatitis. A Rheumatologist will help guide the patient to understanding why the test is positive and whether it suggests lupus or not.
There are pitfalls in interpreting the ANA test. A few years ago the central labs like Quest and LabCorp and others like the Mayo Clinic changed the technique for identifying the ANA using an enzyme linked test (ELISA test) rather than the classic immunofluorescence (IFA) test. This was changed because they could automate their testing process. Central labs have developed the multiplex automated screens to process the large volume of clinical specimens.
Tests using ELISAs and coated beads are not accurate ANA screening tests. The classic ANA immunofluorescent Assay(IFA) test is the gold standard for testing for the ANA, and it uses a biological system, usually mammalian cells, including a kidney cell, liver cell or now the Hep 2 cancer cell (with its large nucleus). HEP 2 cells have hundreds of antigens(proteins and nucleic acids) that are distributed in orderly domains in a tissue culture cell and thus can tests for hundreds of different types of these antinuclear antigens. The ELISA test only identifies about 12 or so antigens, and thus many people with lupus were not readily identified.
Multiplex ANAs have a good ability to detect specific antigens. The automated tests may have a dozen or so nuclear antigens coated on the walls in plastic plates or on beads. These tests are good and specific for the antigens tested but not for screening. Through the American College of Rheumatology ANA task force, this was reviewed and eventually a position paper was published. This went to the College of American Pathologists (CAP) (who certify the labs) and to the labs themselves and encouraged them to do the right thing. Quest now has the ANA by immunofluorescence as a standard test, and it’s easily found on its website. However, LabCorp still uses the ELISA test to screen for ANA, and it’s not readily apparent on its website that it has the IFA. The correct ANA test code to screen for ANA by immunofluorescence at QUEST is 249, LABCORP is 164947 and FANA for Solstas Lab Partners.
These are just a few of the tests in our field. After the appropriate evaluation, these tests are used to help guide the correct diagnosis and treatment in our patients. It is important to emphasize, despite the regulations of CMS to the contrary, that the most cost-effective diagnosis is the correct diagnosis. As rheumatologists we do this.
John A. Goldman, M.D., MACR, FACP, CCD, is chief of rheumatology at St. Joseph’s Hospital, active staff at Northside Hospital and president of The Medical Quarters, P.C. He is rheumatology medical director of the Atlanta Center for Clinical Research. Dr. Goldman is a former clinical professor of medicine at Emory University School of Medicine. Current and former chairman of the Southeast Committee on Rheumatologic Care Network, Southeast Regional Advisory Council and the ACR Committee on Rheumatologic Care.