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Seronegative RA – When Blood Tests Don’t Tell the Entire Story

Diagnosing rheumatoid arthritis in the early stages of the disease is often difficult.1 The diagnostic processes are clinical and not necessarily clear cut in every case and it may take years to accurately diagnose some patients.2 Many factors go into determining if a patient has RA and professional societies like the American College of Rheumatology (ACR) set the guidelines that include such factors as number and type of joints involved, various blood tests, and duration of symptoms (see

What is seronegative RA?

There is no single blood test that without fail proves the existence of RA. In fact, this is one of the areas of research needed in order to help identify and treat patients early in the disease process before permanent damage sets in. It’s not uncommon for patients to display physical symptoms but not show any positive blood tests like rheumatoid factor, anti-citrullinated protein antibodies, or markers for systemic inflammation like sedimentation rate and c-reactive protein.

Seronegative RA includes a wide variety of other conditions

Yet, it is possible to receive a diagnosis of RA without positive blood tests. Such cases may be called seronegative arthritis or undifferentiated arthritis and is seen in up to 30% of cases.3 According to the New York University School of Medicine Rheumatology Division, seronegative arthritis includes a wide variety diseases including psoriatic arthritis, Reiter’s syndrome, enteropathic arthritis, reactive arthritis, ankylosing spondylitis (which actually has it’s own blood test called HLA-B27), undifferentiated seronegative arthritis, Whipple’s disease, and others.4

My experience with seronegative RA

Five years ago I was such a case of seronegative arthritis. Over a period of four years I had two ankle surgeries and a bad case of inflammation in both eyes called uveitis. Then I started to have pain and swelling in my fingers coupled with general fatigue. I went to my primary care physician and after taking a history and conducting a physical exam, he immediately sent me to a rheumatologist. All of the blood tests came back negative. Yet, I had bone erosion in my fingers as shown by x-rays and the doctor put me on disease modifying drugs. After symptoms continued unabated, I quickly progressed to using biological treatments

Seroconversion: from undifferentiated arthritis to RA

After an escalation of symptoms a few years later, my blood tests began coming in positive including rheumatoid factor and c-reactive protein. The official diagnosis in my files changed from undifferentiated arthritis to rheumatoid arthritis. My rheumatologist said that I “seroconverted”. One group of researchers noted that 1/3rd of such cases ultimately turn into RA and another proportion remits.5 Whatever the diagnosis, it is critical that patients receive treatment immediately to arrest permanent tissue damage. In one review of studies about treating patients with undifferentiated arthritis, the authors noted that the treatment plans should follow the same ones used for seropositive RA including DMARDs and biologicals.6

Arthritis rears its ugly head in so many different ways and every patient seems to display a variety of symptoms and blood test results. But the diagnostic criteria are such that even those without positive blood tests, the so-called “seronegative” cases, should still receive a diagnosis and treatment. Hopefully researchers will develop more accurate blood tests that will be able to detect rheumatoid arthritis much earlier so that preventative treatments can begin.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

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  • Kacey
    9 months ago

    I have seronegative RA and I recently had an experience with a provider who basically told me that he didn’t believe I had RA because my tests were negative and wanted me to redo all these tests and essentially “prove” to him that I had it. He was a temporary doctor at my practice because my provider for the last 5 years left and I was not able to get into the other one on staff right away. I was so mad when this happened and it brought up so many insecurities with doctors not believing me that something is wrong. I got so excited when I saw this article because it helped me to know I am not alone out there and don’t need to “prove” anything

  • Kelly Dabel moderator
    9 months ago

    Wow Kacey, thanks for sharing. So glad this article was helpful to you and reminded you that you are not alone here. You have nothing to prove. I hope that you have been able to get in to see your usual doctor. We appreciate you sharing your story. Best, Kelly, Team Member

  • Mary Sophia Hawks moderator
    2 years ago

    Andrew, excellent article! My tests were negative as well, and I have not sero-converted. However, the Vectra DA test did finally show that I have RA. Fortunately, I have a remarkable rheumatologist who listened and believed.

  • Andrew Lumpe, PhD moderator author
    2 years ago

    Glad you liked the article and have a rheumatologist who listens!

  • Corinne
    5 years ago

    It took over five years for me to get diagnosed. I had a caring PCP who couldn’t figure it out, and it took a severe case of anemia and a knowledgeable hemotologist to finally recommend a rheumatologist…..seronegative RA. As soon as i started non biologics I started feeling better. But it took a year to get there….don’t give up hope!

  • Andrew Lumpe, PhD moderator author
    5 years ago

    Corrine, thanks for sharing your story. I’m so glad you had caring docs and you were persistent.

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