To most medical students and patients uninitiated in the science of rheumatology, the diagnostic process whereby rheumatologists assess patients may seem bewildering. When considering any patient who presents with joint pain, there are over 100 types of arthritis to consider, lots of conditions which mimic arthritis, a huge array of blood tests to consider and any amount of expensive imaging tests at our disposal. Sounds complicated? It’s not as hard as it seems. When you take gout and joint infections out of the mix (usually easy to spot if you know what you’re doing), you are really trying to determine if your patient has one of two categories of joint problem; a problem relating to joint degeneration or one relating to inflammation.
Only two types of arthritis to consider. That shouldn’t be too hard to do now should it? Here’s some of blood tests that help us do it;
Inflammation blood tests (ESR, CRP)
The results from these two readily available and relatively inexpensive blood tests are probably the first tests any rheumatologist looks for on a patient are the ESR (‘sed rate’) and CRP. These two complementary blood tests help us differentiate between patients with active inflammatory arthritis (eg rheumatoid, psoriatic, reactive arthritis, undifferentiated inflammatory arthritis, ankylosing spondylitis) and those with degenerative joint problem or with other causes of their pain. Although they can be become elevated in conditions other than arthritis (infections and malignancies for example) I tend look on them as measuring the ‘temperature’ of any inflammatory process. The higher above the normal range they are, the more intense the inflammation present. In certain disease states (eg rheumatoid arthritis), very high levels can help us identify patients at higher risk of damage. The closer to the normal range they are, the less likely a patient it to have an inflammatory process. These tests are also used to help monitor the activity of inflammatory arthritis and its response to treatment (one of the ways we know treatment is working is that the CRP / ESR falls during treatment) These tests are not infallible by any means. For a list of pitfalls in their use see below under specific conditions.
Disease Markers (RF, CCP, ANF/ANA)
Once a doctor suspects a patient has inflammatory arthritis, these disease specific tests are used to determine which type of inflammatory arthritis (or other connective tissue disease) they have. Examples of these tests would be Rheumatoid Factor (RF), CCP antibody and Anti Nuclear antibodies (ANA/ANF).
The majority of rheumatoid arthritis will have a positive rheumatoid factor test (‘seropositive’) or a positive CCP antibody (CCP positive). Rheumatoid factors can also occur in some other conditions (eg SLE, Sjogren’s syndrome) but CCP antibodies are usually only present in patients with rheumatoid arthritis. The presence either of these antibodies can help identify patients who are at greater risk of more severe forms of rheumatoid.
There is also some evidence that these antibodies can be present for many years in people before they develop rheumatoid arthritis so be positive in patients without symptoms. The ANF* is usually positive in SLE but can be positive in patients with rheumatoid arthritis. Confused yet?
*Further discussion of the use of Antinuclear antibodies is beyond the scope of this piece
This is the commonest form or arthritis and a condition where ALL of these blood tests listed above should be normal. That means normal ESR, CRP, RF and CCP antibodies unless there’s another condition present alongside the osteoarthritis.
The ESR or CRP may also be normal in patients newly presenting with rheumatoid arthritis. In a large study of RA patients from Finland and US, between 45-47% of patients had a normal ESR, 44-58% had normal CRP at presentation. BOTH were normal in 33% and 42% of patients**. When a rheumatoid factor test was included, 14-15% of patients had no abnormalities in all 3 tests.
Remember that only 70-80% of patients will have a positive rheumatoid factor or CCP antibody (and one can be positive whether the other is negative so we tend to do both) and even greater percentages of pts will have negative antibodies (‘seronegative arthritis’) early on. Having negative antibodies does not therefore exclude rheumatoid arthritis.
It is also well describedthat inflammation can be visible in the joints using MRI ultrasound scans in patients with known rheumatoid arthritis in the absence of inflammation clinically or on blood tests.** the reason there’s two percentages mentioned is that they looked a patients in two different countries (Finland and USA)
Many patients with psoriatic arthritis (approximtely 50%) will have either normal or near normal ESR and or CRP levels. Patients with Psoriatic arthritis will usually have negative rheumatoid factors and CCP antibodies and Antinuclear factors.
Ankylosing Spondylitis / Undifferentiated spondyloarthritis
Ankylosing Spondylitis is a form of inflammatory arthritis (largely affecting the spine). Whereas abnormal CRP and ESR can be very helpful in making a diagnosis of AS in certain patients with back pain, these tests will only be abnormal in about 50% of patients. The rheumatoid factor, CCP antibodies and ANA should be negative in this group of patients.
Palindromic Rheumatism describes a syndrome where there are recurrent episodes of pain swelling warmth and stiffness of joints. The symptoms can have onset over hours and last days – weeks, before subsiding. However episodes of recurrence form a pattern, with symptom free periods between attacks lasting for weeks to months and some of these patients will go on to develop rheumatoid arthritis. It is not unusual for these patients to have normal inflammatory indices (especially between attacks, when they are well) and approximately 50%will have negative Rheumatoid factor and CCP antibodies.]
Making a diagnosis of inflammatory arthritis in patients is usually straightforward but there are some pitfalls to catch the unwary. Whereas the tests can be unreliable in some settings, with the right history and clinical examination in the hands of an experienced rheumatologist, it is possible to make a diagnosis of inflammatory arthritis and offer effective treatment even where the labs don’t quite fit the picture.