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From Practitioner to Patient: What Is Seronegative Rheumatoid Arthritis?

Managing RA

October 05, 2022

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by Stefanie Remson

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Stella Bard, MD

Medically Reviewed

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by Stefanie Remson

•••••

Stella Bard, MD

Medically Reviewed

•••••

•••••

Welcome to From Practitioner to Patient, a column by Stefanie Remson about living with arthritis. Stefanie is both a nurse practitioner and a patient living with RA. She’s here to share what she has learned from her own experiences as a patient and to demystify the medical side of navigating arthritis through her knowledge as a nurse practitioner.

Welcome back to my column! I wanted to answer a question that I often hear my patients ask: How is it that my labs are negative, but I still have an RA diagnosis? Let me tell you about seronegative RA.

There are two main types of rheumatoid arthritis (RA) in adults: seropositive and seronegative.

Seronegative means that two main diagnostic tests for RA are negative, but you still have a formal diagnosis of RA. Whereas — you guessed it — seropositive refers to positive diagnostic tests for RA.

An estimated 20–25% of RA cases are seronegative. Around 50% are thought to be seronegative in the early disease stage and later become seropositive.

How is it that your labs can be negative, but you can still get this life-altering diagnosis?

We rely so heavily on tests to confirm the status of our health that it can be confusing when tests are negative. Those living with chronic conditions probably don’t need reminding of this — so many of our symptoms can remain invisible to tests.

It can mean diagnosis times for seronegative RA are longer, as more tests are needed to rule out other conditions.

It’s important to raise awareness and understanding of seronegative RA as it can leave you with more questions than answers. So, let’s take it back to basics: How is RA usually diagnosed? How does a seronegative RA diagnosis differ? And what might this mean for your treatment and experience?

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How is RA usually diagnosed?

A diagnosis of RA is done by a rheumatologist. The diagnosis is made based on a thorough physical exam, a variety of imaging studies such as X-rays, MRIs, and ultrasounds, and lastly, different serum (blood) lab tests.

The main lab tests identify the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) in the blood.

Anti-cyclic citrullinated peptide antibodies

Anti-CCPs are antibodies produced by the immune system and are associated with RA. This test is the most specific for RA. It will likely always stay positive, even in states of remission. These antibodies may even show up in blood tests as much as a decade before symptoms do.

Measurements of anti-CCP in those without RA are usually below 20 units. Typically, the higher the result, the more severe the RA is.

Many people have results that read greater than 250 units. This means the number was so high that the lab stops measuring it at that level. This is considered a very elevated number and is treated accordingly.

Rheumatoid factor

RF was the first autoantibody to be discovered in those living with RA. It’s an older, yet less specific test for RA. It can indicate other conditions, but it is still used in conjunction with testing for anti-CCPs.

The normal level of RF is usually 0–20 IU/mL. Higher numbers indicate more inflammation or infection and a positive RF result.

It’s not a very specific test, but it is a very important part of the initial diagnosis.

Interpreting the results

If both anti-CCP and RF are positive for RA, and you have joint symptoms consistent with RA, the diagnosis is named seropositive RA.

Some people can have positive tests for anti-CCP and RF but are asymptomatic. They would not receive a diagnosis (yet). It might be referred to as a subclinical disease, meaning it has not yet become clinically recognizable.

If these lab tests are negative, but the physical exam, imaging, and other information support a diagnosis of RA, then this is called seronegative RA.

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Do any other labs matter when it comes to seronegative RA?

Many other lab values are an important part of the diagnosis of seronegative RA, even when the traditional anti-CCP and RF labs are negative. A lot of these tests aren’t specific for RA but can be valuable assets for a diagnosis and tracking the effectiveness of treatments.

Erythrocyte sedimentation rate

Erythrocyte sedimentation rate (or ESR for short) is a very basic, nonspecific test for inflammation. ESR measurements vary between men and women and may also be higher with increased age.

Those living without an inflammatory condition typically report a reading under 30 mm/hr. Many things can make this number increase besides RA, but this can be valuable to add to the clinical picture as a whole.

C-reactive protein

C-reactive protein, or CRP, is another nonspecific measure of inflammation.

Those living without an inflammatory condition typically report CRP levels of less than 10 mg/L. This number may be higher for those living with RA, but can also be higher in cases of active infection or illness.

Vectra

The Vectra DA lab test is an objective measure of disease activity for patients with RA. It uses 12 biomarkers that are directly tied to RA and the disease activity of RA.

This is measured on a scale of 1–100. This test can help monitor inflammation in RA.

If you have more questions about the Vectra DA test, CreakyJoints has this great reference available.

If you’d like to read about other diagnostic tests, learn more here.

What does seronegative RA actually mean for you?

To put it simply, seronegative RA means that your anti-CCP and RF lab tests are negative. Someone with seronegative RA does not have the same antibodies in their blood as someone with seropositive RA.

But people with seronegative RA often report the same life-altering symptoms as those living with seropositive.

As RA progresses, anti-CCP and RF levels can increase, which can change a diagnosis of seronegative RA to seropositive RA. The clinical management of RA is often the same whether seronegative or seropositive.

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Is seronegative RA worse?

There have been many studies and debates over the years about whether seronegative or seropositive RA may have more severe symptoms or disease progression.

In 2018, this study found that people with seronegative RA had more disease activity before treatment, but they also showed a better response to treatment when compared with people with seropositive RA.

An earlier study in 2013 suggests those living with seronegative RA were more likely to have partial remission. But overall, there was little difference in how the two types affected a person.

Yet because seronegative RA is more difficult to diagnose, the data has simply not been adequate, and more funding is needed. As diagnosis can be delayed for people with seronegative RA, there is also a chance that treatment is delayed, missing out on a crucial window to prevent disease progression and enter remission.

In both types of RA, a treat-to-target (T2T) approach is used to improve overall RA outcomes.

The bottom line: Both are real

Whether you have a diagnosis of seropositive or seronegative RA, the diagnosis of rheumatoid arthritis and the symptoms you report are real.

The results of diagnostic tests aren’t the be-all and end-all. Listen to your body and discuss your symptoms with a rheumatologist.

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About the author

Stefanie Remson

Ms. Stefanie Remson MSN, APRN, FNP-BC is the CEO and founder of RheumatoidArthritisCoach.com. She is a family nurse practitioner and is a rheumatoid arthritis (RA) patient herself. She has spent her entire life serving the community as a healthcare professional and has refused to let RA slow her down. She has worked with The Arthritis Foundation, The Lupus Foundation of America, Healthline, Grace and Able, Arthritis Life, Musculo, Aila, and HopeX. You can learn more at her website and on Instagram, Facebook, and Pinterest.

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