Getting a diagnosis of Seronegative Rheumatoid Arthritis (RA)


Seronegative Rheumatoid Arthritis. That’s me! It’s what my rheumy has suspected all along, but I didn’t completely meet the diagnostic criteria..and frankly he thought I had something worse. But now that I meet the criteria, it’s official.  See?  Told you I was sick!

So what’s changed? My bone scan shows synovitis. And my bloodwork shows some inflammation. My ESR is slightly elevated, and so is my CRP. My RF is still low, hence, seronegative.

What does all that mean?

Firstly, RF or rheumatoid factor. People often refer to this as the ‘RA test’ but it isn’t really accurate. It is an autoantibody that is often, but not always, elevated in Rheumatoid Arthritis. About 70% of people with Rheumatoid Arthritis have a positive RF, but many people have a positive RF but do NOT have Rheumatoid Arthritis. Then there’s the other 30% who clearly have arthritis, but their RF is negative. That’s me. Being seronegative is supposed to correlate with milder disease. I hope that’s true, but I must admit, I’m doubtful.

Next. ESR, or erythrocyte sedimentation rate, or just ‘sed rate’. The test is non-specific, when elevated it shows that there is inflammation in the body. It could be from cancer, pregnancy or, you guessed it, Rheumatoid Arthritis, or any number of other reasons. Together with other signs and symptoms however, it is a useful test for confirming a Rheumatoid Arthritis diagnosis.

On to CRP, or C-Reactive Protein. This is a protein (surprisingly enough) found in the blood, that when elevated, also points to inflammation in the body. It is also non-specific and is a sign of acute inflammation.

And finally, anti-CCP. This stands for anti-cyclic citrullinated peptide antibody, and it’s another blood test which helps your doctor confirm a diagnosis. This is one of the newer Rheumatoid Arthritis markers, and it is very specific for RA – around 95%. It is still not conclusive, however. You can have RA with a negative anti-CCP. It’s just a lot less likely.

These are the basic blood tests. There are more, many more, but these would be the standard tests that a rheumatologist will use to figure out what’s wrong with you. They will also order x-rays, and probably a nuclear bone scan as well.  It is of course possible to have rheumatoid arthritis and have negative RF, ESR and CRP and anti-CCP.

But if all of these tests are negative, its not very likely that you have RA but it is still possible.  But you will not meet the ACR criteria for and RA diagnosis. So you might get a diagnosis of ‘undifferentiated arthritis’ or ‘inflammatory arthritis’ or ‘suspected’ RA rather than Rheumatoid Arthritis.  This is not the same thing as moderate to severe, full blown Rheumatoid Arthritis.

Whatever your exact diagnosis,  good rheumatologist will start treatment, aggressive or not, depending on your symptoms and their experience. Should all the above blood work be negative, it’s statistically likely that its not RA and the arthritis will be mild and self limiting (i.e. go away on its own). There is of course the risk that it will develop into full blown RA, so it can be a hard decision to know how aggressively to treat.

Rheumatologists tend to treat agressively these days, as plenty of studies show that patients have better outcomes, less damage and a higher chance of going into remission with early, agressive treatment.  So if you rheumatologist suspects RA, even if you don’t meet the full criteria they will prescribe a first line DMARD treatment (such as methotrexate, arava and/or sulfasalazine).  Prednisone will often be used to get pain and inflammation under control quickly, as first line DMARDs are slow acting and can take several weeks to show any effect.

There are non aggressive approaches also.  If they suspect your disease is very mild inflammatory arthritis they will prescribe a second line treatment (such as plaquenil alone)  and an anti-inflammatory such as mobic or voltarin.

Rheumatologists are not infallible though…and mild RA can quickly become moderate or severe. Having a rheumatologist monitor your condition is essential.  Most people need NSAIDs (non-steroidal anti-inflammatories) or corticosteroids to get their disease under control.  At least initially.  The aim is ofcourse to take the minimum medications to get rheumatoid arthritis under control.  In severe cases, a patient might take several DMARDS, an NSAID and prednisone.  Just to get out of bed in the morning.

Some doctors use blood test results (ESR and CRP) to measure how severe or active your disease is, although it’s pretty obvious if you actually talk to patients, that many times the blood work and the amount of pain or damage don’t correlate at all. Accurate scans, like ultrasound and nuclear bone scans often tell a better story.  X-rays are quite often clean, because it generally takes time for damage to show on x-ray.

If you’ve never had an x-ray or a bone scan or an ultrasound or an MRI to examine the condition of your joints, your rheumatlogist is either incompetent or very sure you don’t have RA.

X-rays are essential in the initial stages so the progression of the disease can be monitored over time.  It’s a baseline, a starting point.  Some people will start to see damage on their x-rays in a matter of months.  The goal of treatment is to prevent this damage, because once done, it cannot be undone.  If your rheumatologist is treating you and yet your scans show disease progression, they know they need to treat more agressively with more agressive medications.

The doctors are still catching up. There’s so much that isn’t known about inflammatory arthritis, rheumatoid arthritis and auto immune disease in general. But until your blood work shows something, you don’t get an official diagnosis. You get the raised-eyebrow treatment. Or a diagnosis of depression, and a script for anti depressants. Which, if you are depressed (from seeing all these doctors who don’t believe you) might help your mood. But they won’t help your ‘suspected’ arthritis!


  1. I just got home from a Rheumatologist appointment. He said inflammation showed up on X-rays of both hands and both hips but seemed to think it was secondary to some other condition (of which he thought was outside his specialty). It’s interesting that only X-rays and a few blood tests were done and because no MRI was done he could not tell me where the inflammation is; joints? long bones? tendons? I don’t know if that doesn’t matter or whether he neglected to do some tests that might help further pin down a diagnosis. Not sure which diagnostic code he’s using for his billing. He does not think it’s Osteo but doesn’t really think it’s Rheumatoid either; just said he thinks it’s some sort of “Inflammatory Arthritis” and does not have a clue what the underlying condition is. I can’t go on DMARDS because of a history of Hepatis. He scheduled me to follow up in 3 months and is waiting for some other specialist to elucidate my condition further.


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