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 https://rheumatoidarthritis.net/diagnosis/).

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. 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


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 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.  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 RheumatoidArthritis.net 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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