Laboratory tests in Rheumatology- A collection of Myths and Pearls

Laboratory tests are an integral part of medicine. They are helpful in the diagnosis, management & prognostication of disease. However, as is true for any branch in medicine, more so in Rheumatology, lab tests are not absolute & need to be interpreted with caution.

The interpretation of any test depends not only on the sensitivity & specificity of the test, but also on the pre- test probability of the disease in question, & the incidence & prevalence of the disease in the population, as a whole.

Unfortunately, there is no single test which can be considered a gold standard for any of the rheumatic illnesses. There are many important things which need to be considered during the interpretation of any rheumatic test, 10 of which are being highlighted here.


Pearl- There is no such thing as an ‘arthritis panel’?

Tests need to be ordered based on the symptoms, like the pattern of joint involvement- whether mono/ polyarticular, whether or not associated with inflammatory low back pain, systemic features like fever, rash, hair loss, oral ulcers, weight loss, etc.

 Irrational ordering of tests will only confuse the picture, for e.g. ordering for Rheumatoid Factor (RF) in a monoarticular disease & checking Uric Acid levels in a patient with polyarticular disease.


Pearl- The method for testing any antibody is vital.

A few important examples to highlight this fact are as follows:

i) ANA should always be tested by Indirect Immunofluoroscence method. Testing by ELISA carries a high rate of false positivity & false negativity & is not recommended. LE cell phenomenon has been abandoned as a test for SLE & should not be done.

Depending on the pattern of ANA fluorescence, further testing for specific ENAS (Extractable Nuclear Antigens) should be ordered. The table below shows the pattern of fluorescence & the associated antibodies.



ii) As a screening test, ANCA should be checked by Indirect Immunofluoroscence method & depending on the pattern of fluorescence, further testing by ELISA for antibodies against specific antigens like MPO (myeloperoxidase) & PR3 (proteinase 3) can be ordered.


Myth- Hyperuricemia (high uric acid levels) signifies a disease state and should be treated?


Hyperuricemia is a biochemical abnormality & not a disease state. In the presence of hyperuricemia, if the patient has no symptoms (asymptomatic hyperuricemia) as detected during routine health check, then no treatment is indicated.


Myth- A high ASO titer in a patient with joints pains, implies Acute Rheumatic Fever (ARF)

ARF is mainly a disease of children aged 5–14 years. Initial episodes become less common in older adolescents and young adults and are rare in persons aged >30 years. By contrast, recurrent episodes of ARF remain relatively common in adolescents and young adults.

Moreover, ARF causes migratory & not persistent arthritis, as seen in RA. Thus, in an adult with the first episode of persistent polyarthritis, high ASO titers will only mean recent Streptococcal infection, & not ARF.


Myth- A positive RA (Rheumatoid arthritis) test indicates RA.

There is no such thing as RA test, because there is no single test for RA. It is better referred to as RF (Rheumatoid Factor) which has a sensitivity of 60-70% & specificity of 50-60%. This low sensitivity means that negative RF does not rule out the diagnosis of RA. Similarly, a low specificity means that a positive RF does not confirm the diagnosis of RA.

Anti- CCP (anti- Cyclic Citrullinated Peptide) is superior to RF in that it has a high specificity (95-98%) but its sensitivity is as low as RF, which means that a negative anti- CCP does not rule out the diagnosis of RA.


Pearl. HLA B27 positivity alone does not signify a disease state?

HLAB27 gene is present in 6-8% of healthy general population. Thus, in the absence of typical features of Spondyloarthropathy, HLA B27 positivity does not imply illness. Similarly, except for Ankylosing Spondylitis, where HLA B27 is positive >90% of patients, a negative HLA B27 does not rule out the diagnosis of Spondyloarthropathy, as the sensitivity of HLA B27 in other spondyloarthropathies, i.e. reactive arthritis, psoriatic arthritis & enteropathic arthritis, is in the range of 50-80%, depending on the presence of axial/ peripheral symptoms.


Myth- An X ray should be obtained for every painful joint?

An acutely painful joint will only show soft tissue swelling & peril- articular osteopenia, which is non- specific & can be seen in all inflammatory/ infectious conditions. The typical features of RA, namely marginal erosions & joint space narrowing, take 1-2 years to develop & are not useful for early diagnosis.


Pearl- Synovial fluid analysis has limited diagnostic utility



Synovial fluid analysis has a limited role except in crystal arthritis, where demonstration of monosodium urate crystals is the gold standard for the diagnosis of gout. Otherwise it is helpful in differentiating inflammatory from non- inflammatory conditions & is a must in suspected septic arthritis.


Pearl- Anti-beta-2 glycoprotein I is a newly recognized antibody in Anti- Phospholipid Syndrome (APS)



In 2006, revised criteria for the diagnosis of APS were published in an international consensus statement. According to these criteria, in suspected APS, patients must have (1) medium to high levels of immunoglobulin G (IgG) or immunoglobulin M (IgM) anticardiolipin (aCL), (2) anti–beta-2 glycoprotein I, or (3) LA on at least 2 occasions at least 12 weeks apart, to confirm the diagnosis of APS.

It is important to note that these antibodies need to be repeated after at least 12 weeks before making or refuting the diagnosis of APS. Also, LA (lupus anticoagulant) is a functional assay & therefore cannot be tested in patients already on anticoagulants.