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Rheumatoid factor - a lab test update

Chemical pathologist Dr Stuart Smellie uses a primary care case history to discuss the role of rheumatoid factor in diagnosing RA

Chemical pathologist Dr Stuart Smellie uses a primary care case history to discuss the role of rheumatoid factor in diagnosing RA

The case

A 68-year-old lady attends for a follow-up appointment. A few weeks previously, she had seen the GP registrar about joint aches and pains she'd been experiencing for a few weeks. The registrar had noted she had no joint swelling or damage clinically and prescribed an NSAID and arranged some blood tests including rheumatoid factor and CRP.

The rheumatoid factor is reported as positive (40 IU) and the CRP is 5mg/l. The full blood count is normal.

The patient has already rung for her results and is now in a state of agitation, demanding to know what you are going to do about her rheumatoid arthritis.

What is rheumatoid factor?

Rheumatoid factor is a set of antibodies, usually IgM type, directed mostly against the Fc part of human IgG antibodies, although other binding affinities, including to intracellular components, have been found. It can be found in rheumatoid arthritis and a wide range of other autoimmune, infectious and haematological diseases. It is also found in the healthy population.

How likely is it that a patient with rheumatoid arthritis will have a positive test? What other conditions can give a similar result?

About 70-90% of people with rheumatoid arthritis have rheumatoid factor – depending on the population examined – although, as mentioned, a range of other diseases, particularly those involving chronic immune stimulation, can cause a raised rheumatoid factor. A negative rheumatoid factor does not exclude rheumatoid arthritis.

Newer tests such as anti-cyclic citrullinated peptide (anti-CCP) antibody assays are far more specific for rheumatoid arthritis and some rheumatologists are now using them to help diagnose or exclude rheumatoid arthritis with far more confidence. Talk to your rheumatologist – it's a relatively specialist test and not available everywhere.

What's the prevalence of a positive rheumatoid factor test in the normal population?

Rheumatoid factor is quite common in the general population, particularly in older people. Prevalence is about 1% in the general population, but this rises to 10-20% in people over 65. Therefore it has absolutely no role as a routine screening test in healthy people as it would produce many more false positives than true positives for rheumatoid arthritis. It becomes more useful when the pre-test probability of rheumatoid arthritis rises.

The key factor here is whether the arthritis is inflammatory, when it takes on a positive predictive value of around 75% and a negative predictive value of about 90%.

In this case I would bring the patient to surgery and tell her that this was a very crude screening test which probably shouldn't have been done, because in reality it was more likely to give a false positive result as she does not have features of inflammatory arthritis.

It may help to talk to a rheumatologist or the lab to try to arrange an anti-CCP antibody test as this will almost certainly be negative and provide reassurance.

The features of inflammatory arthritis are:

• joint swelling

• joint damage/deformity

• raised CRP (or ESR, although ESR also rises with age making it hard to interpret).

What are the main differences between rheumatoid factor-positive and rheumatoid factor-negative inflammatory arthritis?

Inflammatory arthritis that is negative for rheumatoid factor consists of a range of arthritic conditions, which include rheumatoid arthritis itself, but also joint manifestations of the spectrum of connective disuse diseases, from lupus to scleroderma.

The way of distinguishing these other diseases, apart from their clinical features, is by their autoantibody pattern in serum, so autoantibodies should be requested if one of these is suspected.

Rheumatoid arthritis that is negative for rheumatoid factor is usually a less aggressive disease.

Rheumatoid factor-positive rheumatoid arthritis with high titres (more than 100 IU) is more often associated with severe and extra-articular rheumatoid disease.

Can the test be used confidently for diagnosis, or is it only of prognostic value?

Because of its high prevalence in the population, it is only useful diagnostically if inflammatory arthritis has been identified. In the general population, its positive predictive value is only about 10% – many times worse than tossing a coin, and given many people's understanding of rheumatoid arthritis as an often crippling disease, it is liable to cause far more patient concern than benefit.

Does it have any value in disease monitoring?

No. It has no role in disease monitoring in rheumatoid arthritis. Apart from clinical response to any treatment, if a laboratory marker is needed changes in C-reactive protein or ESR are the most useful. There are one or two very specific situations in which it is being looked at outside of rheumatoid arthritis, such as in Sjogren's syndrome, but these are isolated and still a bit speculative.

Dr Stuart Smellie is consultant chemical pathologist at Bishop Auckland Hospital, County Durham, and Darlington NHS Foundation Trust

Competing interests: None declared

Lab test update Related Seminar: Musculoskeletal Medicine

Clinical Seminar: Musculoskeletal Medicine

What: A one day refresher to update GPs on the hot issues and trickiest dilemmas in rheumatology and orthopaedics.

When: Thursday 5 November 2009

Where: Raddison Hotel, Manchester

Next steps: Find out more and book

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